Expert Commentary

Voiding dysfunction—either difficulty voiding or urinary retention—after surgery for stress incontinence distresses the patient and challenges the surgeon. Here is our systematic approach to evaluating and managing such cases.

What does the operative note say?

Determine exactly what operation the patient underwent and whether appropriate steps were taken during surgery to evaluate the lower urinary tract. Remember: There are well over 30 different synthetic midurethral slings on the market; a variety of biologic materials are used for slings; and conventional suspension procedures are still being performed. Sling composition and surgical technique are the major determinants of subsequent treatment, so it is imperative to obtain the operative note.

Is intermittent self-catheterization an option?

If the patient has an indwelling catheter—of any type—remove it whenever possible and teach her intermittent self-catheterization.

Are symptoms consistent with expected outcome?

In the case of a patient who had a large cystocele repair in conjunction with an anti-incontinence procedure, for example, it is common for some form of retention or voiding dysfunction to be present for 2 weeks or longer. On the other hand, if a patient had a synthetic midurethral sling but no other procedure, it is highly unlikely, during a normal postoperative course, that she would be in retention 2 weeks after the procedure—unless the sling was placed too tightly.

Is there actual (or impending) lower-tract injury? Foreign body penetration?

Good endoscopic evaluation, with visualization of the urethra, of the vesical neck and anterolateral walls of the bladder, will answer these questions.

What is the condition of the pelvic floor?

Make certain that the patient has the ability to appropriately relax the pelvic floor when she attempts to void.

Is urethral dilatation or medication an option?

We believe that urethral dilatation is contraindicated because it might cause urethral erosion of the sling. It is also generally ineffective.

No pharmaceutical agent hastens the return of voiding. Cholinergic agents such as bethanechol are ineffective and cause considerable discomfort. Some experts recommend empiric diazepam (Valium) for patients who are unable to relax sufficiently.

Will intervention succeed?

Ultimately, you and the patient must agree on whether urethrolysis is to be performed or whether the suburethral sling or tape should be cut. Undertake a detailed discussion with her about the potential for, first, persistent voiding dysfunction and, second, recurrent stress incontinence. Cutting a synthetic, allograft, xenograft, or autologous sling will almost always result in resumption of normal voiding, provided the sling is appropriately detached from the urethra and there were no preoperative voiding symptoms. With synthetic, allograft, and xenograft slings, stress incontinence recurs in at least 50% of patients over time. With an autologous sling, the recurrence rate of stress incontinence is less than 10%.

Is it time to operate?

When urinary retention after a synthetic sling procedure is believed to be caused by obstruction, consider surgery within a few weeks. For a patient in retention who has an autologous, allograft, or xenograft sling, it is best to wait approximately 3 months before operating.

Be aware of the risk of failure!

Takedowns of Burch and Marshall-Marchetti operations are much more technically challenging, and yield a much lower success rate, than takedowns of sling procedures. No matter what the prior operation, there is a risk of recurrent sphincteric incontinence.

Voiding dysfunction—either difficulty voiding or urinary retention—after surgery for stress incontinence distresses the patient and challenges the surgeon. Here is our systematic approach to evaluating and managing such cases.

What does the operative note say?

Determine exactly what operation the patient underwent and whether appropriate steps were taken during surgery to evaluate the lower urinary tract. Remember: There are well over 30 different synthetic midurethral slings on the market; a variety of biologic materials are used for slings; and conventional suspension procedures are still being performed. Sling composition and surgical technique are the major determinants of subsequent treatment, so it is imperative to obtain the operative note.

Is intermittent self-catheterization an option?

If the patient has an indwelling catheter—of any type—remove it whenever possible and teach her intermittent self-catheterization.

Are symptoms consistent with expected outcome?

In the case of a patient who had a large cystocele repair in conjunction with an anti-incontinence procedure, for example, it is common for some form of retention or voiding dysfunction to be present for 2 weeks or longer. On the other hand, if a patient had a synthetic midurethral sling but no other procedure, it is highly unlikely, during a normal postoperative course, that she would be in retention 2 weeks after the procedure—unless the sling was placed too tightly.

Is there actual (or impending) lower-tract injury? Foreign body penetration?

Good endoscopic evaluation, with visualization of the urethra, of the vesical neck and anterolateral walls of the bladder, will answer these questions.

What is the condition of the pelvic floor?

Make certain that the patient has the ability to appropriately relax the pelvic floor when she attempts to void.

Is urethral dilatation or medication an option?

We believe that urethral dilatation is contraindicated because it might cause urethral erosion of the sling. It is also generally ineffective.

No pharmaceutical agent hastens the return of voiding. Cholinergic agents such as bethanechol are ineffective and cause considerable discomfort. Some experts recommend empiric diazepam (Valium) for patients who are unable to relax sufficiently.

Will intervention succeed?

Ultimately, you and the patient must agree on whether urethrolysis is to be performed or whether the suburethral sling or tape should be cut. Undertake a detailed discussion with her about the potential for, first, persistent voiding dysfunction and, second, recurrent stress incontinence. Cutting a synthetic, allograft, xenograft, or autologous sling will almost always result in resumption of normal voiding, provided the sling is appropriately detached from the urethra and there were no preoperative voiding symptoms. With synthetic, allograft, and xenograft slings, stress incontinence recurs in at least 50% of patients over time. With an autologous sling, the recurrence rate of stress incontinence is less than 10%.

Is it time to operate?

When urinary retention after a synthetic sling procedure is believed to be caused by obstruction, consider surgery within a few weeks. For a patient in retention who has an autologous, allograft, or xenograft sling, it is best to wait approximately 3 months before operating.

Be aware of the risk of failure!

Takedowns of Burch and Marshall-Marchetti operations are much more technically challenging, and yield a much lower success rate, than takedowns of sling procedures. No matter what the prior operation, there is a risk of recurrent sphincteric incontinence.

Voiding dysfunction—either difficulty voiding or urinary retention—after surgery for stress incontinence distresses the patient and challenges the surgeon. Here is our systematic approach to evaluating and managing such cases.

What does the operative note say?

Determine exactly what operation the patient underwent and whether appropriate steps were taken during surgery to evaluate the lower urinary tract. Remember: There are well over 30 different synthetic midurethral slings on the market; a variety of biologic materials are used for slings; and conventional suspension procedures are still being performed. Sling composition and surgical technique are the major determinants of subsequent treatment, so it is imperative to obtain the operative note.

Is intermittent self-catheterization an option?

If the patient has an indwelling catheter—of any type—remove it whenever possible and teach her intermittent self-catheterization.

Are symptoms consistent with expected outcome?

In the case of a patient who had a large cystocele repair in conjunction with an anti-incontinence procedure, for example, it is common for some form of retention or voiding dysfunction to be present for 2 weeks or longer. On the other hand, if a patient had a synthetic midurethral sling but no other procedure, it is highly unlikely, during a normal postoperative course, that she would be in retention 2 weeks after the procedure—unless the sling was placed too tightly.

Is there actual (or impending) lower-tract injury? Foreign body penetration?

Good endoscopic evaluation, with visualization of the urethra, of the vesical neck and anterolateral walls of the bladder, will answer these questions.

What is the condition of the pelvic floor?

Make certain that the patient has the ability to appropriately relax the pelvic floor when she attempts to void.

Is urethral dilatation or medication an option?

We believe that urethral dilatation is contraindicated because it might cause urethral erosion of the sling. It is also generally ineffective.

No pharmaceutical agent hastens the return of voiding. Cholinergic agents such as bethanechol are ineffective and cause considerable discomfort. Some experts recommend empiric diazepam (Valium) for patients who are unable to relax sufficiently.

Will intervention succeed?

Ultimately, you and the patient must agree on whether urethrolysis is to be performed or whether the suburethral sling or tape should be cut. Undertake a detailed discussion with her about the potential for, first, persistent voiding dysfunction and, second, recurrent stress incontinence. Cutting a synthetic, allograft, xenograft, or autologous sling will almost always result in resumption of normal voiding, provided the sling is appropriately detached from the urethra and there were no preoperative voiding symptoms. With synthetic, allograft, and xenograft slings, stress incontinence recurs in at least 50% of patients over time. With an autologous sling, the recurrence rate of stress incontinence is less than 10%.

Is it time to operate?

When urinary retention after a synthetic sling procedure is believed to be caused by obstruction, consider surgery within a few weeks. For a patient in retention who has an autologous, allograft, or xenograft sling, it is best to wait approximately 3 months before operating.

Be aware of the risk of failure!

Takedowns of Burch and Marshall-Marchetti operations are much more technically challenging, and yield a much lower success rate, than takedowns of sling procedures. No matter what the prior operation, there is a risk of recurrent sphincteric incontinence.

What once seemed far in the future is now a reality: the human papillomavirus (HPV) vaccine. The quadrivalent vaccine (Gardasil) that prevents the development of lesions caused by HPV types 6, 11, 16, and 18 was approved last June by the US Food and Drug Administration (FDA) for clinical use in females 9 to 26 years old. Shortly after its approval, the Advisory Committee on Immunization Practices (ACIP) issued guidelines on who should be vaccinated.

In light of these developments, OBG Management invited Dr. Tom Wright to convene an expert panel to discuss the ACIP recommendations and ways of introducing the vaccine into practice.

ACIP recommends vaccination at age 11 or 12

WRIGHT: Dr. DeFrancesco, would you review the ACIP recommendations for us?

DeFRANCESCO: Shortly after the FDA approved Gardasil, the quadrivalent vaccine (Merck, Whitehouse Station, NJ), the ACIP recommended routine vaccination with 3 doses for girls aged 11 or 12 years, but noted that vaccination is also acceptable for girls as young as 9 at the discretion of the physician or health-care provider. The new 2006–2007 Recommended Adult Immunization Schedule states that the HPV vaccine is “recommended for all women aged ≤26 years of age” (available at www.cdc.gov/nip/recs/adult-schedule).

Ideally, the vaccine should be given before the onset of sexual activity (ie, before a woman is exposed to the virus), but sexually active girls and women through 26 years should still be vaccinated, as they are not likely to have been exposed to all 4 HPV types covered by the vaccine.

ACOG recommendations mirror those of ACIP

WRIGHT: Dr. Gall, are ACOG’s recommendations similar to the ACIP’s?

GALL: Yes. They mirror those of the ACIP, as they recommend that:

Should sexually active women be vaccinated?

WRIGHT: Both the ACIP and ACOG suggest that we encourage “catch-up” vaccination of sexually active women through 26 years. However, many experts disagree, arguing that vaccination of this population may not be worth the effort.

Dr. Gall, why does ACOG recommend that sexually active women get vaccinated?

GALL: Data from the Merck Phase III trials indicate that only 25% of women at age 23 are either serologically or DNA positive for 1 of the 4 HPV types included in the quadrivalent vaccine and that only 0.1% of women are positive for all 4 vaccine HPV types. Data on HPV 16 from the National Health and Nutrition Examination Surveys (NHANES), conducted by the Centers for Disease Control and Prevention (CDC), are in line with this estimate. It is pretty clear that most sexually active women aged 26 or younger will benefit from vaccination.

Vaccine may benefit even women with high-risk sexual practices

WRIGHT: OK, Dr. Levy, you heard Dr. Gall say we should vaccinate sexually active women. Are you convinced? What are you going to tell a 24-year-old single woman who has had 12 lifetime sexual partners?

LEVY: I would tell her that she is extremely likely to have been infected with 1 or more HPV strains—but unlikely to have been exposed to all 4 types present in the vaccine. I would also explain that the vaccine is almost 100% effective at preventing genital warts caused by HPV 6 and 11 and will prevent both infections and lesions with HPV types 16 and/or 18 if the patient has not been exposed to them.

The benefit for this 24-year-old may not be as great as it is for our primary target population of preteens not yet exposed to HPV, but vaccination can reduce the disease burden—even in a woman who has had multiple sexual partners.

If this patient has already had genital warts and an abnormal Pap smear, or is positive for high-risk HPV DNA, the benefit would be even lower. Ultimately, she will have to decide whether the cost is worth the lessened benefit in her situation.

Lessons learned from the hepatitis B experience

WRIGHT: One of the things we learned 20 years ago when we introduced the hepatitis B vaccine is that limiting vaccination to groups expected to gain the most benefit doesn’t work very well. With hepatitis B, we initially targeted only high-risk groups such as intravenous drug users, men who have sex with men, and health-care workers—but this strategy didn’t reduce the rate of hepatitis to the extent expected. Once we recommended universal vaccination of the general population, however, a rapid reduction in hepatitis B occurred.

 

In many respects HPV is like hepatitis B. I have heard some experts say that we may eventually vaccinate all at-risk women—essentially, all sexually active women.

Vaccinate women over age 26?

WRIGHT: Women older than 26 are already asking whether they should be vaccinated. What do we know about the safety and efficacy of the vaccine in these women?

GALL: Even though the number of women infected with at least 1 HPV type, or who have evidence of such infection, exceeds 60% by age 50, only a small number of women will have been exposed to all 4 HPV types covered by the vaccine. Thus, it seems likely that sexually active women over age 26 will benefit from vaccination.

The safety data on the vaccine are excellent. In our experience, the quadrivalent vaccine has been less reactogenic than the influenza vaccine. There is no reason to suspect that the HPV vaccine will be less safe in women over age 26.

Recently, immunogenicity data for the bivalent vaccine—not yet approved by the FDA—were presented to the American Society of Clinical Oncology for women aged 26 to 55 years, and excellent immune responses were observed. All we need to recommend vaccination of sexually active women over age 26 is the efficacy data, and I see no reason to think that the HPV vaccine will not be effective.

Counsel older women about off-label use

WRIGHT: What would you tell a recently divorced 32-year-old who got married in college, has had only a couple of partners, and is beginning to date again?

DeFRANCESCO: The vaccine is approved and recommended only for females aged 9 to 26, so vaccinating an older woman would be off-label—or “off-recommendation,” as those who specialize in vaccination say.

We also know that the immune system is generally more responsive in younger people, although the immunogenicity data that Dr. Gall just mentioned indicate that the bivalent HPV vaccine is highly immunogenic in older women. I would be hard-pressed to deny the apparent protection of the vaccine to a 32-year-old woman simply because she is over age 26.

However, given the medicolegal climate, I would ensure that informed consent includes a caveat about use of the vaccine in someone outside the approved age range and makes it clear that the patient has acknowledged being informed about the “off-recommendation” use.

Readers will want to know that Phase III trials are now assessing the safety and efficacy of the quadrivalent and bivalent vaccines in women over 26; data should be available in the next couple of years.

WRIGHT: I agree completely. In today’s litigious world, it is vital to counsel women appropriately and obtain informed consent prior to any vaccination. One way to educate the patient about potential benefits and risks is by providing her with a Vaccine Information Sheet, available for download from the CDC’s Web site (www.cdc.gov/nip/publications/VIS/default.htm#hpv).

Can an adolescent give her own consent?

WRIGHT: It has not yet been fully clarified whether a sexually active adolescent can provide consent on her own, or whether a parent must sign the consent form. Most states have laws that allow at least some adolescents to seek reproductive services, as well as screening and treatment for sexually transmitted diseases, without parental notification. However, at several meetings I attended recently, lawyers specializing in the legal rights of adolescents said it remains unclear which of these state laws extend to the HPV vaccine.

DeFRANCESCO: I’ve been told the same thing by our legal advisors. Pending clarification, it is important to emphasize to our patients that the vaccine is a cancer vaccine, not a drug to prevent sexually transmitted infection. The vaccine does not give young people “permission” to have sex, but helps prevent them from ever developing cervical cancer. Young people should not have to sneak around to get this protection.

Who will pay for it?

WRIGHT: One of the really big issues is how we are going to pay for the HPV vaccine, which has a list price of $120 per dose and requires 3 injections. If you add the cost of 3 office visits, that’s almost $500.

LEVY: Most insurance companies in our area have already determined that they will cover the HPV vaccine. Even carriers that are usually slow to make coverage decisions added the HPV vaccine to their list of covered services fairly promptly.

WRIGHT: That’s good news for people who have health insurance. What about women who don’t, or who have high deductibles or carve-outs for “preventive services”?

Patients may be willing to foot the bill

 

LEVY: I have been discussing the vaccine with eligible women and mothers of young girls for several months. Even before payers stepped up with coverage, no patient was seriously concerned about the cost. Clearly, this will not be true for everyone, but when offered an opportunity to avoid cancer, my patients have been happy to pay for it. In addition, many offices now accept credit cards, which may make it possible for patients to make payments over time.

I think success will depend in large part on how we educate our patients. I frequently discuss preventive care in the context of other things we do in our lives for “maintenance.” For example, none of us would expect our automobile insurance to cover the cost of changing the oil or buying new tires. The HPV vaccine is comparable: The costs incurred now may prevent significant health risks in the near future.

Further, the price of the vaccine series is quite low relative to the potential costs of office visits for follow-up of abnormal Pap smears or treatment of genital warts.

We must stress to our patients that Pap smears aid in the detection of cervical cancer precursors, but the vaccine is an opportunity to prevent cervical cancer.

The poor and uninsured have several alternatives

WRIGHT: In the predominantly Latin American neighborhood where I am located, there are many uninsured who simply cannot afford $500 for the full course of 3 vaccinations. For uninsured children and adolescents, or those on Medicaid up to age 19, the federally funded Vaccines for Children program will cover the cost. However, for women aged 19 and older, vaccinations are considered an “optional” benefit under Medicaid, which means that individual states must decide whether the HPV vaccine will be a covered service.

One bit of good news: Merck plans to provide free vaccines, including the HPV vaccine, to low-income and uninsured adults 19 years and older who visit private clinicians who already provide Merck vaccines. Although the details of this initiative have not been finalized, the program may help individuals in states that decide not to cover the HPV vaccine with Medicaid.

Vaccine appears safe near time of conception

WRIGHT: I have heard varying opinions about the level of risk vaccination poses if a woman becomes pregnant shortly afterward. What do the data show?

GALL: It is inevitable that this vaccine will be administered to some women who are not yet aware they are pregnant. In the Merck trials, more than 1,000 pregnancies occurred in both the vaccine and placebo groups. There were 15 abnormal infants in the vaccine group and 16 in the placebo group. The abnormalities were nonrepetitive and did not raise concern at the FDA.

Among the women who received an injection within 30 days of conception, there were 5 abnormalities, compared with none in the placebo group—but none of the abnormalities were repetitive and some involved such things as an extra digit.

The vaccine was accorded a pregnancy category B. This is a landmark for the FDA because no other vaccine has this designation, even those used extensively during pregnancy, such as the trivalent inactivated influenza vaccine (TIV) and hepatitis B.

At present, clinicians are asked to report any women who receive the quadrivalent vaccine and become pregnant, but I can foresee a time when we will administer this vaccine during pregnancy.

How ObGyns are reacting

WRIGHT: Dr. DeFrancesco, you are involved in managing almost 200 ObGyns. How do you expect the specialty to respond to the new vaccine?

DeFRANCESCO: Vaccination is not a traditional ObGyn responsibility, but I think most of us are comfortable administering other injections, such as Rho(D) immune globulin, leuprolide acetate, and depot medroxyprogesterone acetate, or even hepatitis B vaccines for our staff. The HPV vaccine is a different injection with a different purpose, but well within our expertise to administer. I am pleased to report that—in record time!—all our practices are offering the vaccine and implementing this new service. It clearly is the right thing to do.

ObGyns need to build a vaccination infrastructure

WRIGHT: There are related issues: maintaining stocks of vaccine in ObGyn offices, developing and using consent forms, and implementing a tracking system to make sure patients get all 3 injections of the vaccine. How are you addressing these issues?

DeFRANCESCO: We have implemented a clinical guideline consistent with the ACIP and ACOG policy statements, along with a model informed consent and insurance waiver within our large group practice. This helps us ensure that providers are up-to-date on the latest recommendations and are ready to provide this service.

 

If patients are concerned about the potential cost, we advise them to check with their carriers. We also ask them to sign a waiver that will permit us to bill the patient herself if she is not covered.

In addition, we have set up an account for each of our practices with the vaccine manufacturer so we can order vaccine on fairly short notice. We have recommended that our divisions each stock a reasonable number of doses to ensure enough supply to meet the demand expected in the very near future. We have also recommended that our practices go ahead and schedule the 2- and 6-month booster visits at the time of the patient’s first vaccination and counsel the patient about the importance of receiving all 3 doses.

ACOG hopes to create better (and bigger) vaccinators

GALL: In general, ObGyns don’t do a very good job at vaccinating. The last CDC survey I saw indicated that less than 60% of ObGyns collect immunization and infection histories from their patients, and only two thirds offer even a single vaccine.

WRIGHT: You have been working for several years to help the ObGyn community with vaccine implementation. What is ACOG doing to help physicians in private practice?

GALL: ACOG has promoted the concept that ObGyns should, and need to, become better vaccinators. A working committee on immunization has developed a program for practicing ObGyns. The concept is simple: The HPV vaccine is an ObGyn vaccine, and we should embrace it with vigor. If the ObGyn office gets set up to administer the HPV vaccine, why not administer other important vaccines such as TIV, hepatitis B, Tdap, MCV4, and herpes zoster?

This working committee has prepared a number of materials that should be available by the next annual clinical meeting:

We also plan presentations for the district and annual clinical meetings.

Is there a future for cervical cancer screening?

WRIGHT: Dr. Levy, can you explain why we are going to need to continue screening once the vaccine becomes widely used?

LEVY: For the next 30 to 40 years we will have a large population of women—already over age 26—who have not received the vaccine. These women will require ongoing screening for cervical cancer precursors throughout their lives.

Although the vaccine protects against HPV types 16 and 18, which cause 70% of cancer cases, and types 6 and 11, which cause 90% of genital warts, immunity to these HPV types will not protect a woman against the other 11 high-risk HPV types. These 11 types are not as commonly associated with cervical cancer or its precursors, but they do lead to cancer in some women and can still infect the cervix in women who have received the vaccine. Even if we reach all at-risk young women with our vaccine program, they will still be at risk—albeit lower risk—for cervical cancer due to infection with other high-risk HPV types.

One other point: We do not yet know how long the immunity from these vaccines will last. So it seems clear that screening will still be required to detect cervical cancer precursors and prevent cervical cancer from developing—even in women who have received the HPV vaccine.

Do we risk increasing the cancer rate?

WRIGHT: I worry about vaccination coverage. In the absence of state school requirements for the HPV vaccine, we are unlikely to get a high coverage rate among adolescents in the US. In several European countries, such as Germany, that have both recommendations and funding for universal hepatitis B vaccination of adolescents, only about 30% of adolescents have been vaccinated. The reason? These countries lack school requirements for the vaccination and have no school-based vaccination program. With the high prevalence of HPV infections in young, sexually active women in the US, we could actually increase our cervical cancer rate if we recommend reduced screening without ensuring high levels of vaccination coverage.

Dr. Gall, what do you predict for the next decade?

GALL: The future looks bright. A bipartisan bill was just introduced in the Michigan state legislature to add the HPV vaccine as a requirement for entry into junior high school. I expect more states to follow.

In general, adolescents are a poorly served group when it comes to health care because many fall out of the system. The HPV vaccine provides a great opportunity for us to encourage patients to bring their adolescent daughters to the office for a consultation. During this visit, we will conduct an “about the umbilicus” (ie, non-pelvic) physical exam, provide immunization, and discuss a number of topics such as contraception, menstruation, nutrition, etc. A critical step is to get state health departments and Medicaid officials off the dime and supporting the HPV vaccine.

 

Drs. Wright, DeFrancesco, Gall, and Levy report no financial relationships relevant to this article.

What once seemed far in the future is now a reality: the human papillomavirus (HPV) vaccine. The quadrivalent vaccine (Gardasil) that prevents the development of lesions caused by HPV types 6, 11, 16, and 18 was approved last June by the US Food and Drug Administration (FDA) for clinical use in females 9 to 26 years old. Shortly after its approval, the Advisory Committee on Immunization Practices (ACIP) issued guidelines on who should be vaccinated.

In light of these developments, OBG Management invited Dr. Tom Wright to convene an expert panel to discuss the ACIP recommendations and ways of introducing the vaccine into practice.

ACIP recommends vaccination at age 11 or 12

WRIGHT: Dr. DeFrancesco, would you review the ACIP recommendations for us?

DeFRANCESCO: Shortly after the FDA approved Gardasil, the quadrivalent vaccine (Merck, Whitehouse Station, NJ), the ACIP recommended routine vaccination with 3 doses for girls aged 11 or 12 years, but noted that vaccination is also acceptable for girls as young as 9 at the discretion of the physician or health-care provider. The new 2006–2007 Recommended Adult Immunization Schedule states that the HPV vaccine is “recommended for all women aged ≤26 years of age” (available at www.cdc.gov/nip/recs/adult-schedule).

Ideally, the vaccine should be given before the onset of sexual activity (ie, before a woman is exposed to the virus), but sexually active girls and women through 26 years should still be vaccinated, as they are not likely to have been exposed to all 4 HPV types covered by the vaccine.

ACOG recommendations mirror those of ACIP

WRIGHT: Dr. Gall, are ACOG’s recommendations similar to the ACIP’s?

GALL: Yes. They mirror those of the ACIP, as they recommend that:

Should sexually active women be vaccinated?

WRIGHT: Both the ACIP and ACOG suggest that we encourage “catch-up” vaccination of sexually active women through 26 years. However, many experts disagree, arguing that vaccination of this population may not be worth the effort.

Dr. Gall, why does ACOG recommend that sexually active women get vaccinated?

GALL: Data from the Merck Phase III trials indicate that only 25% of women at age 23 are either serologically or DNA positive for 1 of the 4 HPV types included in the quadrivalent vaccine and that only 0.1% of women are positive for all 4 vaccine HPV types. Data on HPV 16 from the National Health and Nutrition Examination Surveys (NHANES), conducted by the Centers for Disease Control and Prevention (CDC), are in line with this estimate. It is pretty clear that most sexually active women aged 26 or younger will benefit from vaccination.

Vaccine may benefit even women with high-risk sexual practices

WRIGHT: OK, Dr. Levy, you heard Dr. Gall say we should vaccinate sexually active women. Are you convinced? What are you going to tell a 24-year-old single woman who has had 12 lifetime sexual partners?

LEVY: I would tell her that she is extremely likely to have been infected with 1 or more HPV strains—but unlikely to have been exposed to all 4 types present in the vaccine. I would also explain that the vaccine is almost 100% effective at preventing genital warts caused by HPV 6 and 11 and will prevent both infections and lesions with HPV types 16 and/or 18 if the patient has not been exposed to them.

The benefit for this 24-year-old may not be as great as it is for our primary target population of preteens not yet exposed to HPV, but vaccination can reduce the disease burden—even in a woman who has had multiple sexual partners.

If this patient has already had genital warts and an abnormal Pap smear, or is positive for high-risk HPV DNA, the benefit would be even lower. Ultimately, she will have to decide whether the cost is worth the lessened benefit in her situation.

Lessons learned from the hepatitis B experience

WRIGHT: One of the things we learned 20 years ago when we introduced the hepatitis B vaccine is that limiting vaccination to groups expected to gain the most benefit doesn’t work very well. With hepatitis B, we initially targeted only high-risk groups such as intravenous drug users, men who have sex with men, and health-care workers—but this strategy didn’t reduce the rate of hepatitis to the extent expected. Once we recommended universal vaccination of the general population, however, a rapid reduction in hepatitis B occurred.

 

In many respects HPV is like hepatitis B. I have heard some experts say that we may eventually vaccinate all at-risk women—essentially, all sexually active women.

Vaccinate women over age 26?

WRIGHT: Women older than 26 are already asking whether they should be vaccinated. What do we know about the safety and efficacy of the vaccine in these women?

GALL: Even though the number of women infected with at least 1 HPV type, or who have evidence of such infection, exceeds 60% by age 50, only a small number of women will have been exposed to all 4 HPV types covered by the vaccine. Thus, it seems likely that sexually active women over age 26 will benefit from vaccination.

The safety data on the vaccine are excellent. In our experience, the quadrivalent vaccine has been less reactogenic than the influenza vaccine. There is no reason to suspect that the HPV vaccine will be less safe in women over age 26.

Recently, immunogenicity data for the bivalent vaccine—not yet approved by the FDA—were presented to the American Society of Clinical Oncology for women aged 26 to 55 years, and excellent immune responses were observed. All we need to recommend vaccination of sexually active women over age 26 is the efficacy data, and I see no reason to think that the HPV vaccine will not be effective.

Counsel older women about off-label use

WRIGHT: What would you tell a recently divorced 32-year-old who got married in college, has had only a couple of partners, and is beginning to date again?

DeFRANCESCO: The vaccine is approved and recommended only for females aged 9 to 26, so vaccinating an older woman would be off-label—or “off-recommendation,” as those who specialize in vaccination say.

We also know that the immune system is generally more responsive in younger people, although the immunogenicity data that Dr. Gall just mentioned indicate that the bivalent HPV vaccine is highly immunogenic in older women. I would be hard-pressed to deny the apparent protection of the vaccine to a 32-year-old woman simply because she is over age 26.

However, given the medicolegal climate, I would ensure that informed consent includes a caveat about use of the vaccine in someone outside the approved age range and makes it clear that the patient has acknowledged being informed about the “off-recommendation” use.

Readers will want to know that Phase III trials are now assessing the safety and efficacy of the quadrivalent and bivalent vaccines in women over 26; data should be available in the next couple of years.

WRIGHT: I agree completely. In today’s litigious world, it is vital to counsel women appropriately and obtain informed consent prior to any vaccination. One way to educate the patient about potential benefits and risks is by providing her with a Vaccine Information Sheet, available for download from the CDC’s Web site (www.cdc.gov/nip/publications/VIS/default.htm#hpv).

Can an adolescent give her own consent?

WRIGHT: It has not yet been fully clarified whether a sexually active adolescent can provide consent on her own, or whether a parent must sign the consent form. Most states have laws that allow at least some adolescents to seek reproductive services, as well as screening and treatment for sexually transmitted diseases, without parental notification. However, at several meetings I attended recently, lawyers specializing in the legal rights of adolescents said it remains unclear which of these state laws extend to the HPV vaccine.

DeFRANCESCO: I’ve been told the same thing by our legal advisors. Pending clarification, it is important to emphasize to our patients that the vaccine is a cancer vaccine, not a drug to prevent sexually transmitted infection. The vaccine does not give young people “permission” to have sex, but helps prevent them from ever developing cervical cancer. Young people should not have to sneak around to get this protection.

Who will pay for it?

WRIGHT: One of the really big issues is how we are going to pay for the HPV vaccine, which has a list price of $120 per dose and requires 3 injections. If you add the cost of 3 office visits, that’s almost $500.

LEVY: Most insurance companies in our area have already determined that they will cover the HPV vaccine. Even carriers that are usually slow to make coverage decisions added the HPV vaccine to their list of covered services fairly promptly.

WRIGHT: That’s good news for people who have health insurance. What about women who don’t, or who have high deductibles or carve-outs for “preventive services”?

Patients may be willing to foot the bill

 

LEVY: I have been discussing the vaccine with eligible women and mothers of young girls for several months. Even before payers stepped up with coverage, no patient was seriously concerned about the cost. Clearly, this will not be true for everyone, but when offered an opportunity to avoid cancer, my patients have been happy to pay for it. In addition, many offices now accept credit cards, which may make it possible for patients to make payments over time.

I think success will depend in large part on how we educate our patients. I frequently discuss preventive care in the context of other things we do in our lives for “maintenance.” For example, none of us would expect our automobile insurance to cover the cost of changing the oil or buying new tires. The HPV vaccine is comparable: The costs incurred now may prevent significant health risks in the near future.

Further, the price of the vaccine series is quite low relative to the potential costs of office visits for follow-up of abnormal Pap smears or treatment of genital warts.

We must stress to our patients that Pap smears aid in the detection of cervical cancer precursors, but the vaccine is an opportunity to prevent cervical cancer.

The poor and uninsured have several alternatives

WRIGHT: In the predominantly Latin American neighborhood where I am located, there are many uninsured who simply cannot afford $500 for the full course of 3 vaccinations. For uninsured children and adolescents, or those on Medicaid up to age 19, the federally funded Vaccines for Children program will cover the cost. However, for women aged 19 and older, vaccinations are considered an “optional” benefit under Medicaid, which means that individual states must decide whether the HPV vaccine will be a covered service.

One bit of good news: Merck plans to provide free vaccines, including the HPV vaccine, to low-income and uninsured adults 19 years and older who visit private clinicians who already provide Merck vaccines. Although the details of this initiative have not been finalized, the program may help individuals in states that decide not to cover the HPV vaccine with Medicaid.

Vaccine appears safe near time of conception

WRIGHT: I have heard varying opinions about the level of risk vaccination poses if a woman becomes pregnant shortly afterward. What do the data show?

GALL: It is inevitable that this vaccine will be administered to some women who are not yet aware they are pregnant. In the Merck trials, more than 1,000 pregnancies occurred in both the vaccine and placebo groups. There were 15 abnormal infants in the vaccine group and 16 in the placebo group. The abnormalities were nonrepetitive and did not raise concern at the FDA.

Among the women who received an injection within 30 days of conception, there were 5 abnormalities, compared with none in the placebo group—but none of the abnormalities were repetitive and some involved such things as an extra digit.

The vaccine was accorded a pregnancy category B. This is a landmark for the FDA because no other vaccine has this designation, even those used extensively during pregnancy, such as the trivalent inactivated influenza vaccine (TIV) and hepatitis B.

At present, clinicians are asked to report any women who receive the quadrivalent vaccine and become pregnant, but I can foresee a time when we will administer this vaccine during pregnancy.

How ObGyns are reacting

WRIGHT: Dr. DeFrancesco, you are involved in managing almost 200 ObGyns. How do you expect the specialty to respond to the new vaccine?

DeFRANCESCO: Vaccination is not a traditional ObGyn responsibility, but I think most of us are comfortable administering other injections, such as Rho(D) immune globulin, leuprolide acetate, and depot medroxyprogesterone acetate, or even hepatitis B vaccines for our staff. The HPV vaccine is a different injection with a different purpose, but well within our expertise to administer. I am pleased to report that—in record time!—all our practices are offering the vaccine and implementing this new service. It clearly is the right thing to do.

ObGyns need to build a vaccination infrastructure

WRIGHT: There are related issues: maintaining stocks of vaccine in ObGyn offices, developing and using consent forms, and implementing a tracking system to make sure patients get all 3 injections of the vaccine. How are you addressing these issues?

DeFRANCESCO: We have implemented a clinical guideline consistent with the ACIP and ACOG policy statements, along with a model informed consent and insurance waiver within our large group practice. This helps us ensure that providers are up-to-date on the latest recommendations and are ready to provide this service.

 

If patients are concerned about the potential cost, we advise them to check with their carriers. We also ask them to sign a waiver that will permit us to bill the patient herself if she is not covered.

In addition, we have set up an account for each of our practices with the vaccine manufacturer so we can order vaccine on fairly short notice. We have recommended that our divisions each stock a reasonable number of doses to ensure enough supply to meet the demand expected in the very near future. We have also recommended that our practices go ahead and schedule the 2- and 6-month booster visits at the time of the patient’s first vaccination and counsel the patient about the importance of receiving all 3 doses.

ACOG hopes to create better (and bigger) vaccinators

GALL: In general, ObGyns don’t do a very good job at vaccinating. The last CDC survey I saw indicated that less than 60% of ObGyns collect immunization and infection histories from their patients, and only two thirds offer even a single vaccine.

WRIGHT: You have been working for several years to help the ObGyn community with vaccine implementation. What is ACOG doing to help physicians in private practice?

GALL: ACOG has promoted the concept that ObGyns should, and need to, become better vaccinators. A working committee on immunization has developed a program for practicing ObGyns. The concept is simple: The HPV vaccine is an ObGyn vaccine, and we should embrace it with vigor. If the ObGyn office gets set up to administer the HPV vaccine, why not administer other important vaccines such as TIV, hepatitis B, Tdap, MCV4, and herpes zoster?

This working committee has prepared a number of materials that should be available by the next annual clinical meeting:

We also plan presentations for the district and annual clinical meetings.

Is there a future for cervical cancer screening?

WRIGHT: Dr. Levy, can you explain why we are going to need to continue screening once the vaccine becomes widely used?

LEVY: For the next 30 to 40 years we will have a large population of women—already over age 26—who have not received the vaccine. These women will require ongoing screening for cervical cancer precursors throughout their lives.

Although the vaccine protects against HPV types 16 and 18, which cause 70% of cancer cases, and types 6 and 11, which cause 90% of genital warts, immunity to these HPV types will not protect a woman against the other 11 high-risk HPV types. These 11 types are not as commonly associated with cervical cancer or its precursors, but they do lead to cancer in some women and can still infect the cervix in women who have received the vaccine. Even if we reach all at-risk young women with our vaccine program, they will still be at risk—albeit lower risk—for cervical cancer due to infection with other high-risk HPV types.

One other point: We do not yet know how long the immunity from these vaccines will last. So it seems clear that screening will still be required to detect cervical cancer precursors and prevent cervical cancer from developing—even in women who have received the HPV vaccine.

Do we risk increasing the cancer rate?

WRIGHT: I worry about vaccination coverage. In the absence of state school requirements for the HPV vaccine, we are unlikely to get a high coverage rate among adolescents in the US. In several European countries, such as Germany, that have both recommendations and funding for universal hepatitis B vaccination of adolescents, only about 30% of adolescents have been vaccinated. The reason? These countries lack school requirements for the vaccination and have no school-based vaccination program. With the high prevalence of HPV infections in young, sexually active women in the US, we could actually increase our cervical cancer rate if we recommend reduced screening without ensuring high levels of vaccination coverage.

Dr. Gall, what do you predict for the next decade?

GALL: The future looks bright. A bipartisan bill was just introduced in the Michigan state legislature to add the HPV vaccine as a requirement for entry into junior high school. I expect more states to follow.

In general, adolescents are a poorly served group when it comes to health care because many fall out of the system. The HPV vaccine provides a great opportunity for us to encourage patients to bring their adolescent daughters to the office for a consultation. During this visit, we will conduct an “about the umbilicus” (ie, non-pelvic) physical exam, provide immunization, and discuss a number of topics such as contraception, menstruation, nutrition, etc. A critical step is to get state health departments and Medicaid officials off the dime and supporting the HPV vaccine.

 

Drs. Wright, DeFrancesco, Gall, and Levy report no financial relationships relevant to this article.

What once seemed far in the future is now a reality: the human papillomavirus (HPV) vaccine. The quadrivalent vaccine (Gardasil) that prevents the development of lesions caused by HPV types 6, 11, 16, and 18 was approved last June by the US Food and Drug Administration (FDA) for clinical use in females 9 to 26 years old. Shortly after its approval, the Advisory Committee on Immunization Practices (ACIP) issued guidelines on who should be vaccinated.

In light of these developments, OBG Management invited Dr. Tom Wright to convene an expert panel to discuss the ACIP recommendations and ways of introducing the vaccine into practice.

ACIP recommends vaccination at age 11 or 12

WRIGHT: Dr. DeFrancesco, would you review the ACIP recommendations for us?

DeFRANCESCO: Shortly after the FDA approved Gardasil, the quadrivalent vaccine (Merck, Whitehouse Station, NJ), the ACIP recommended routine vaccination with 3 doses for girls aged 11 or 12 years, but noted that vaccination is also acceptable for girls as young as 9 at the discretion of the physician or health-care provider. The new 2006–2007 Recommended Adult Immunization Schedule states that the HPV vaccine is “recommended for all women aged ≤26 years of age” (available at www.cdc.gov/nip/recs/adult-schedule).

Ideally, the vaccine should be given before the onset of sexual activity (ie, before a woman is exposed to the virus), but sexually active girls and women through 26 years should still be vaccinated, as they are not likely to have been exposed to all 4 HPV types covered by the vaccine.

ACOG recommendations mirror those of ACIP

WRIGHT: Dr. Gall, are ACOG’s recommendations similar to the ACIP’s?

GALL: Yes. They mirror those of the ACIP, as they recommend that:

Should sexually active women be vaccinated?

WRIGHT: Both the ACIP and ACOG suggest that we encourage “catch-up” vaccination of sexually active women through 26 years. However, many experts disagree, arguing that vaccination of this population may not be worth the effort.

Dr. Gall, why does ACOG recommend that sexually active women get vaccinated?

GALL: Data from the Merck Phase III trials indicate that only 25% of women at age 23 are either serologically or DNA positive for 1 of the 4 HPV types included in the quadrivalent vaccine and that only 0.1% of women are positive for all 4 vaccine HPV types. Data on HPV 16 from the National Health and Nutrition Examination Surveys (NHANES), conducted by the Centers for Disease Control and Prevention (CDC), are in line with this estimate. It is pretty clear that most sexually active women aged 26 or younger will benefit from vaccination.

Vaccine may benefit even women with high-risk sexual practices

WRIGHT: OK, Dr. Levy, you heard Dr. Gall say we should vaccinate sexually active women. Are you convinced? What are you going to tell a 24-year-old single woman who has had 12 lifetime sexual partners?

LEVY: I would tell her that she is extremely likely to have been infected with 1 or more HPV strains—but unlikely to have been exposed to all 4 types present in the vaccine. I would also explain that the vaccine is almost 100% effective at preventing genital warts caused by HPV 6 and 11 and will prevent both infections and lesions with HPV types 16 and/or 18 if the patient has not been exposed to them.

The benefit for this 24-year-old may not be as great as it is for our primary target population of preteens not yet exposed to HPV, but vaccination can reduce the disease burden—even in a woman who has had multiple sexual partners.

If this patient has already had genital warts and an abnormal Pap smear, or is positive for high-risk HPV DNA, the benefit would be even lower. Ultimately, she will have to decide whether the cost is worth the lessened benefit in her situation.

Lessons learned from the hepatitis B experience

WRIGHT: One of the things we learned 20 years ago when we introduced the hepatitis B vaccine is that limiting vaccination to groups expected to gain the most benefit doesn’t work very well. With hepatitis B, we initially targeted only high-risk groups such as intravenous drug users, men who have sex with men, and health-care workers—but this strategy didn’t reduce the rate of hepatitis to the extent expected. Once we recommended universal vaccination of the general population, however, a rapid reduction in hepatitis B occurred.

 

In many respects HPV is like hepatitis B. I have heard some experts say that we may eventually vaccinate all at-risk women—essentially, all sexually active women.

Vaccinate women over age 26?

WRIGHT: Women older than 26 are already asking whether they should be vaccinated. What do we know about the safety and efficacy of the vaccine in these women?

GALL: Even though the number of women infected with at least 1 HPV type, or who have evidence of such infection, exceeds 60% by age 50, only a small number of women will have been exposed to all 4 HPV types covered by the vaccine. Thus, it seems likely that sexually active women over age 26 will benefit from vaccination.

The safety data on the vaccine are excellent. In our experience, the quadrivalent vaccine has been less reactogenic than the influenza vaccine. There is no reason to suspect that the HPV vaccine will be less safe in women over age 26.

Recently, immunogenicity data for the bivalent vaccine—not yet approved by the FDA—were presented to the American Society of Clinical Oncology for women aged 26 to 55 years, and excellent immune responses were observed. All we need to recommend vaccination of sexually active women over age 26 is the efficacy data, and I see no reason to think that the HPV vaccine will not be effective.

Counsel older women about off-label use

WRIGHT: What would you tell a recently divorced 32-year-old who got married in college, has had only a couple of partners, and is beginning to date again?

DeFRANCESCO: The vaccine is approved and recommended only for females aged 9 to 26, so vaccinating an older woman would be off-label—or “off-recommendation,” as those who specialize in vaccination say.

We also know that the immune system is generally more responsive in younger people, although the immunogenicity data that Dr. Gall just mentioned indicate that the bivalent HPV vaccine is highly immunogenic in older women. I would be hard-pressed to deny the apparent protection of the vaccine to a 32-year-old woman simply because she is over age 26.

However, given the medicolegal climate, I would ensure that informed consent includes a caveat about use of the vaccine in someone outside the approved age range and makes it clear that the patient has acknowledged being informed about the “off-recommendation” use.

Readers will want to know that Phase III trials are now assessing the safety and efficacy of the quadrivalent and bivalent vaccines in women over 26; data should be available in the next couple of years.

WRIGHT: I agree completely. In today’s litigious world, it is vital to counsel women appropriately and obtain informed consent prior to any vaccination. One way to educate the patient about potential benefits and risks is by providing her with a Vaccine Information Sheet, available for download from the CDC’s Web site (www.cdc.gov/nip/publications/VIS/default.htm#hpv).

Can an adolescent give her own consent?

WRIGHT: It has not yet been fully clarified whether a sexually active adolescent can provide consent on her own, or whether a parent must sign the consent form. Most states have laws that allow at least some adolescents to seek reproductive services, as well as screening and treatment for sexually transmitted diseases, without parental notification. However, at several meetings I attended recently, lawyers specializing in the legal rights of adolescents said it remains unclear which of these state laws extend to the HPV vaccine.

DeFRANCESCO: I’ve been told the same thing by our legal advisors. Pending clarification, it is important to emphasize to our patients that the vaccine is a cancer vaccine, not a drug to prevent sexually transmitted infection. The vaccine does not give young people “permission” to have sex, but helps prevent them from ever developing cervical cancer. Young people should not have to sneak around to get this protection.

Who will pay for it?

WRIGHT: One of the really big issues is how we are going to pay for the HPV vaccine, which has a list price of $120 per dose and requires 3 injections. If you add the cost of 3 office visits, that’s almost $500.

LEVY: Most insurance companies in our area have already determined that they will cover the HPV vaccine. Even carriers that are usually slow to make coverage decisions added the HPV vaccine to their list of covered services fairly promptly.

WRIGHT: That’s good news for people who have health insurance. What about women who don’t, or who have high deductibles or carve-outs for “preventive services”?

Patients may be willing to foot the bill

 

LEVY: I have been discussing the vaccine with eligible women and mothers of young girls for several months. Even before payers stepped up with coverage, no patient was seriously concerned about the cost. Clearly, this will not be true for everyone, but when offered an opportunity to avoid cancer, my patients have been happy to pay for it. In addition, many offices now accept credit cards, which may make it possible for patients to make payments over time.

I think success will depend in large part on how we educate our patients. I frequently discuss preventive care in the context of other things we do in our lives for “maintenance.” For example, none of us would expect our automobile insurance to cover the cost of changing the oil or buying new tires. The HPV vaccine is comparable: The costs incurred now may prevent significant health risks in the near future.

Further, the price of the vaccine series is quite low relative to the potential costs of office visits for follow-up of abnormal Pap smears or treatment of genital warts.

We must stress to our patients that Pap smears aid in the detection of cervical cancer precursors, but the vaccine is an opportunity to prevent cervical cancer.

The poor and uninsured have several alternatives

WRIGHT: In the predominantly Latin American neighborhood where I am located, there are many uninsured who simply cannot afford $500 for the full course of 3 vaccinations. For uninsured children and adolescents, or those on Medicaid up to age 19, the federally funded Vaccines for Children program will cover the cost. However, for women aged 19 and older, vaccinations are considered an “optional” benefit under Medicaid, which means that individual states must decide whether the HPV vaccine will be a covered service.

One bit of good news: Merck plans to provide free vaccines, including the HPV vaccine, to low-income and uninsured adults 19 years and older who visit private clinicians who already provide Merck vaccines. Although the details of this initiative have not been finalized, the program may help individuals in states that decide not to cover the HPV vaccine with Medicaid.

Vaccine appears safe near time of conception

WRIGHT: I have heard varying opinions about the level of risk vaccination poses if a woman becomes pregnant shortly afterward. What do the data show?

GALL: It is inevitable that this vaccine will be administered to some women who are not yet aware they are pregnant. In the Merck trials, more than 1,000 pregnancies occurred in both the vaccine and placebo groups. There were 15 abnormal infants in the vaccine group and 16 in the placebo group. The abnormalities were nonrepetitive and did not raise concern at the FDA.

Among the women who received an injection within 30 days of conception, there were 5 abnormalities, compared with none in the placebo group—but none of the abnormalities were repetitive and some involved such things as an extra digit.

The vaccine was accorded a pregnancy category B. This is a landmark for the FDA because no other vaccine has this designation, even those used extensively during pregnancy, such as the trivalent inactivated influenza vaccine (TIV) and hepatitis B.

At present, clinicians are asked to report any women who receive the quadrivalent vaccine and become pregnant, but I can foresee a time when we will administer this vaccine during pregnancy.

How ObGyns are reacting

WRIGHT: Dr. DeFrancesco, you are involved in managing almost 200 ObGyns. How do you expect the specialty to respond to the new vaccine?

DeFRANCESCO: Vaccination is not a traditional ObGyn responsibility, but I think most of us are comfortable administering other injections, such as Rho(D) immune globulin, leuprolide acetate, and depot medroxyprogesterone acetate, or even hepatitis B vaccines for our staff. The HPV vaccine is a different injection with a different purpose, but well within our expertise to administer. I am pleased to report that—in record time!—all our practices are offering the vaccine and implementing this new service. It clearly is the right thing to do.

ObGyns need to build a vaccination infrastructure

WRIGHT: There are related issues: maintaining stocks of vaccine in ObGyn offices, developing and using consent forms, and implementing a tracking system to make sure patients get all 3 injections of the vaccine. How are you addressing these issues?

DeFRANCESCO: We have implemented a clinical guideline consistent with the ACIP and ACOG policy statements, along with a model informed consent and insurance waiver within our large group practice. This helps us ensure that providers are up-to-date on the latest recommendations and are ready to provide this service.

 

If patients are concerned about the potential cost, we advise them to check with their carriers. We also ask them to sign a waiver that will permit us to bill the patient herself if she is not covered.

In addition, we have set up an account for each of our practices with the vaccine manufacturer so we can order vaccine on fairly short notice. We have recommended that our divisions each stock a reasonable number of doses to ensure enough supply to meet the demand expected in the very near future. We have also recommended that our practices go ahead and schedule the 2- and 6-month booster visits at the time of the patient’s first vaccination and counsel the patient about the importance of receiving all 3 doses.

ACOG hopes to create better (and bigger) vaccinators

GALL: In general, ObGyns don’t do a very good job at vaccinating. The last CDC survey I saw indicated that less than 60% of ObGyns collect immunization and infection histories from their patients, and only two thirds offer even a single vaccine.

WRIGHT: You have been working for several years to help the ObGyn community with vaccine implementation. What is ACOG doing to help physicians in private practice?

GALL: ACOG has promoted the concept that ObGyns should, and need to, become better vaccinators. A working committee on immunization has developed a program for practicing ObGyns. The concept is simple: The HPV vaccine is an ObGyn vaccine, and we should embrace it with vigor. If the ObGyn office gets set up to administer the HPV vaccine, why not administer other important vaccines such as TIV, hepatitis B, Tdap, MCV4, and herpes zoster?

This working committee has prepared a number of materials that should be available by the next annual clinical meeting:

We also plan presentations for the district and annual clinical meetings.

Is there a future for cervical cancer screening?

WRIGHT: Dr. Levy, can you explain why we are going to need to continue screening once the vaccine becomes widely used?

LEVY: For the next 30 to 40 years we will have a large population of women—already over age 26—who have not received the vaccine. These women will require ongoing screening for cervical cancer precursors throughout their lives.

Although the vaccine protects against HPV types 16 and 18, which cause 70% of cancer cases, and types 6 and 11, which cause 90% of genital warts, immunity to these HPV types will not protect a woman against the other 11 high-risk HPV types. These 11 types are not as commonly associated with cervical cancer or its precursors, but they do lead to cancer in some women and can still infect the cervix in women who have received the vaccine. Even if we reach all at-risk young women with our vaccine program, they will still be at risk—albeit lower risk—for cervical cancer due to infection with other high-risk HPV types.

One other point: We do not yet know how long the immunity from these vaccines will last. So it seems clear that screening will still be required to detect cervical cancer precursors and prevent cervical cancer from developing—even in women who have received the HPV vaccine.

Do we risk increasing the cancer rate?

WRIGHT: I worry about vaccination coverage. In the absence of state school requirements for the HPV vaccine, we are unlikely to get a high coverage rate among adolescents in the US. In several European countries, such as Germany, that have both recommendations and funding for universal hepatitis B vaccination of adolescents, only about 30% of adolescents have been vaccinated. The reason? These countries lack school requirements for the vaccination and have no school-based vaccination program. With the high prevalence of HPV infections in young, sexually active women in the US, we could actually increase our cervical cancer rate if we recommend reduced screening without ensuring high levels of vaccination coverage.

Dr. Gall, what do you predict for the next decade?

GALL: The future looks bright. A bipartisan bill was just introduced in the Michigan state legislature to add the HPV vaccine as a requirement for entry into junior high school. I expect more states to follow.

In general, adolescents are a poorly served group when it comes to health care because many fall out of the system. The HPV vaccine provides a great opportunity for us to encourage patients to bring their adolescent daughters to the office for a consultation. During this visit, we will conduct an “about the umbilicus” (ie, non-pelvic) physical exam, provide immunization, and discuss a number of topics such as contraception, menstruation, nutrition, etc. A critical step is to get state health departments and Medicaid officials off the dime and supporting the HPV vaccine.

 

Drs. Wright, DeFrancesco, Gall, and Levy report no financial relationships relevant to this article.

A Both regimens appear to be effective and well-tolerated, but neither is as effective as the gold standard of high-dose, intravenous estrogen.

For the purposes of this study, acute uterine bleeding is excessive or prolonged bleeding that necessitates urgent or emergent intervention. As Munro and colleagues point out, it is a “substantial drain on health-care resources” because so many women with this complaint require hospitalization for surgical intervention. Among the options are dilation and curettage, endometrial ablation, uterine artery embolization, and hysterectomy, the definitive “cure.”

Expert Commentary

In the United States, acute menorrhagia affects at least 10% of the female population and requires immediate attention. Surgical management is generally reserved for the hemodynamically unstable patient, for those who fail medical management, and for those in whom medical management is contraindicated. The gold standard is high-dose, intravenous estrogen, which halts bleeding in 72% of women within 5 hours.

Although combination oral contraceptives (OCs) are frequently used for acute uterine bleeding, a 2000 Cochrane Review¹ found only 1 randomized controlled trial comparing OCs with other medical therapies—and none with comparison with placebo. The Cochrane Review concluded there is not enough evidence to draw any conclusions about the efficacy of combined OCs for menorrhagia.

Until now, support for the use of combination OCs for this indication has been based primarily on textbooks and expert opinion, and we have very little information on the degree of patient satisfaction with the method.

Progesterone-dominant regimens are not as effective as estrogen

Munro and colleagues aimed to correct the paucity of data by treating women with acute menorrhagia with either combined high-dose OCs or high-dose medroxyprogesterone acetate (MPA). Unfortunately, both therapeutic regimens are progesterone-dominant. Estrogen is the gold standard because it stabilizes the endometrial lining by promoting rapid regrowth. Progesterone impedes the action of estrogen, making it less likely to be effective.

A placebo group was believed to be potentially unethical due to the outpatient nature of the study, but a better comparison could have been achieved with an estrogen-only arm.

Sample size fell far below initial projections

Another difficulty with this study is the level of enrollment (n=40), which was far below the number needed (n=400), based on the initial power analysis. Reasons given for the small sample include bias of the referring clinician and patient, and the refusal of many women to submit to randomization. It is difficult to draw significant conclusions based on such a small sample.

What this study reveals

Despite its shortcomings, this study does offer some new information. In the primary outcome of the study—avoidance of emergent surgery—both therapies appeared to be effective, with only 1 patient requiring an unscheduled surgical procedure during the 4 weeks of follow-up. At 2 weeks of follow-up, bleeding had stopped in 76% and 88% of the MPA- and OC-treated patients, respectively. Side effects were minimal in both groups.

Intravenous estrogen is still the gold standard

Although Munro and colleagues add to our understanding of treatments for acute uterine bleeding, estrogen remains the gold standard. Intravenous estrogen is indicated in the inpatient setting for up to 24 hours, followed by tapering to an oral regimen. High-dose oral estrogen is used in the outpatient setting until a significant reduction or cessation of bleeding occurs.

Progesterone therapy should be started in close sequence with estrogen to minimize the likelihood of heavy withdrawal bleeding.

A Both regimens appear to be effective and well-tolerated, but neither is as effective as the gold standard of high-dose, intravenous estrogen.

For the purposes of this study, acute uterine bleeding is excessive or prolonged bleeding that necessitates urgent or emergent intervention. As Munro and colleagues point out, it is a “substantial drain on health-care resources” because so many women with this complaint require hospitalization for surgical intervention. Among the options are dilation and curettage, endometrial ablation, uterine artery embolization, and hysterectomy, the definitive “cure.”

Expert Commentary

In the United States, acute menorrhagia affects at least 10% of the female population and requires immediate attention. Surgical management is generally reserved for the hemodynamically unstable patient, for those who fail medical management, and for those in whom medical management is contraindicated. The gold standard is high-dose, intravenous estrogen, which halts bleeding in 72% of women within 5 hours.

Although combination oral contraceptives (OCs) are frequently used for acute uterine bleeding, a 2000 Cochrane Review¹ found only 1 randomized controlled trial comparing OCs with other medical therapies—and none with comparison with placebo. The Cochrane Review concluded there is not enough evidence to draw any conclusions about the efficacy of combined OCs for menorrhagia.

Until now, support for the use of combination OCs for this indication has been based primarily on textbooks and expert opinion, and we have very little information on the degree of patient satisfaction with the method.

Progesterone-dominant regimens are not as effective as estrogen

Munro and colleagues aimed to correct the paucity of data by treating women with acute menorrhagia with either combined high-dose OCs or high-dose medroxyprogesterone acetate (MPA). Unfortunately, both therapeutic regimens are progesterone-dominant. Estrogen is the gold standard because it stabilizes the endometrial lining by promoting rapid regrowth. Progesterone impedes the action of estrogen, making it less likely to be effective.

A placebo group was believed to be potentially unethical due to the outpatient nature of the study, but a better comparison could have been achieved with an estrogen-only arm.

Sample size fell far below initial projections

Another difficulty with this study is the level of enrollment (n=40), which was far below the number needed (n=400), based on the initial power analysis. Reasons given for the small sample include bias of the referring clinician and patient, and the refusal of many women to submit to randomization. It is difficult to draw significant conclusions based on such a small sample.

What this study reveals

Despite its shortcomings, this study does offer some new information. In the primary outcome of the study—avoidance of emergent surgery—both therapies appeared to be effective, with only 1 patient requiring an unscheduled surgical procedure during the 4 weeks of follow-up. At 2 weeks of follow-up, bleeding had stopped in 76% and 88% of the MPA- and OC-treated patients, respectively. Side effects were minimal in both groups.

Intravenous estrogen is still the gold standard

Although Munro and colleagues add to our understanding of treatments for acute uterine bleeding, estrogen remains the gold standard. Intravenous estrogen is indicated in the inpatient setting for up to 24 hours, followed by tapering to an oral regimen. High-dose oral estrogen is used in the outpatient setting until a significant reduction or cessation of bleeding occurs.

Progesterone therapy should be started in close sequence with estrogen to minimize the likelihood of heavy withdrawal bleeding.

A Both regimens appear to be effective and well-tolerated, but neither is as effective as the gold standard of high-dose, intravenous estrogen.

For the purposes of this study, acute uterine bleeding is excessive or prolonged bleeding that necessitates urgent or emergent intervention. As Munro and colleagues point out, it is a “substantial drain on health-care resources” because so many women with this complaint require hospitalization for surgical intervention. Among the options are dilation and curettage, endometrial ablation, uterine artery embolization, and hysterectomy, the definitive “cure.”

Expert Commentary

In the United States, acute menorrhagia affects at least 10% of the female population and requires immediate attention. Surgical management is generally reserved for the hemodynamically unstable patient, for those who fail medical management, and for those in whom medical management is contraindicated. The gold standard is high-dose, intravenous estrogen, which halts bleeding in 72% of women within 5 hours.

Although combination oral contraceptives (OCs) are frequently used for acute uterine bleeding, a 2000 Cochrane Review¹ found only 1 randomized controlled trial comparing OCs with other medical therapies—and none with comparison with placebo. The Cochrane Review concluded there is not enough evidence to draw any conclusions about the efficacy of combined OCs for menorrhagia.

Until now, support for the use of combination OCs for this indication has been based primarily on textbooks and expert opinion, and we have very little information on the degree of patient satisfaction with the method.

Progesterone-dominant regimens are not as effective as estrogen

Munro and colleagues aimed to correct the paucity of data by treating women with acute menorrhagia with either combined high-dose OCs or high-dose medroxyprogesterone acetate (MPA). Unfortunately, both therapeutic regimens are progesterone-dominant. Estrogen is the gold standard because it stabilizes the endometrial lining by promoting rapid regrowth. Progesterone impedes the action of estrogen, making it less likely to be effective.

A placebo group was believed to be potentially unethical due to the outpatient nature of the study, but a better comparison could have been achieved with an estrogen-only arm.

Sample size fell far below initial projections

Another difficulty with this study is the level of enrollment (n=40), which was far below the number needed (n=400), based on the initial power analysis. Reasons given for the small sample include bias of the referring clinician and patient, and the refusal of many women to submit to randomization. It is difficult to draw significant conclusions based on such a small sample.

What this study reveals

Despite its shortcomings, this study does offer some new information. In the primary outcome of the study—avoidance of emergent surgery—both therapies appeared to be effective, with only 1 patient requiring an unscheduled surgical procedure during the 4 weeks of follow-up. At 2 weeks of follow-up, bleeding had stopped in 76% and 88% of the MPA- and OC-treated patients, respectively. Side effects were minimal in both groups.

Intravenous estrogen is still the gold standard

Although Munro and colleagues add to our understanding of treatments for acute uterine bleeding, estrogen remains the gold standard. Intravenous estrogen is indicated in the inpatient setting for up to 24 hours, followed by tapering to an oral regimen. High-dose oral estrogen is used in the outpatient setting until a significant reduction or cessation of bleeding occurs.

Progesterone therapy should be started in close sequence with estrogen to minimize the likelihood of heavy withdrawal bleeding.

A Yes, according to this retrospective study, provided the practitioner has adequate training and experience. The authors analyzed 20 years of experience and found that the risk of pregnancy loss diminished over time for both test methods, but the reduction was more pronounced in women undergoing chorionic villus sampling (CVS). By the final epoch of study (1998–2003), there was no significant difference between the 2 methods.

Expert Commentary

Caughey and colleagues launched their study to explore the following questions: What is the rate of pregnancy loss in women who undergo CVS and amniocentesis, compared with those who do not? Has the higher rate of pregnancy loss associated with CVS changed over the past 20 years?

That invasive diagnostic procedures have a learning curve is no surprise.¹ It generally follows that the more efficient an operator becomes at a given invasive test, the lower the rate of complications. The clinical question facing us after this study is how valid the comparison is between the 2 procedures, even in the final 5-year epoch.

Study design is laudable

Caughey and colleagues did an admirable job of compiling data on nearly 10,000 CVS tests and 31,000 amniocentesis procedures and their associated clinical outcomes. The fact that this investigation was based at a single center with good follow-up is a definite strength. Also laudable is the attempt to control for background loss rate by adjusting for gestational age at the time of sampling in multivariable analysis, as well as the identification of a control group that underwent neither test.

The investigators also restrain themselves from extrapolating their conclusions or overstating their findings given the nonrandomized nature of the study.

Route of CVS was not specified

Unfortunately, we are not told whether the CVS procedures were performed transcervically, transabdominally, or using both approaches (as is common in many modern programs). Earlier reports involving transcervical sampling found a clear relationship between proximity of the placenta and cervix, as well as uterine position, and the risk of pregnancy loss.² That is one reason centers began to choose the sampling route based largely on placental location.^3,4 If the sampling route was individualized in this study, then the observations can be generalized to programs using a similar approach.

Other potential weaknesses (also cited by the authors) include limited demographic data among the entire population for habits or preconditions that might confound pregnancy loss, such as tobacco use and socioeconomic status. The mixture of experienced clinicians and trainees is another concern, although the authors claim they were equally distributed over the time frame.

More definitive answers are needed

Although this study will be useful in counseling patients who are considering invasive testing, it fails to answer the question of safety definitively. Such an answer requires randomization prior to CVS or the limiting of both procedures to the same gestational age range.

In the most recent head-to-head comparisons at similar gestational ages (11–14 weeks), CVS appears to be safer than amniocentesis.^5,6 The same cannot be said for testing later in the mid-trimester, when amniocentesis is usually performed and has a well-established track record for safety.

A Yes, according to this retrospective study, provided the practitioner has adequate training and experience. The authors analyzed 20 years of experience and found that the risk of pregnancy loss diminished over time for both test methods, but the reduction was more pronounced in women undergoing chorionic villus sampling (CVS). By the final epoch of study (1998–2003), there was no significant difference between the 2 methods.

Expert Commentary

Caughey and colleagues launched their study to explore the following questions: What is the rate of pregnancy loss in women who undergo CVS and amniocentesis, compared with those who do not? Has the higher rate of pregnancy loss associated with CVS changed over the past 20 years?

That invasive diagnostic procedures have a learning curve is no surprise.¹ It generally follows that the more efficient an operator becomes at a given invasive test, the lower the rate of complications. The clinical question facing us after this study is how valid the comparison is between the 2 procedures, even in the final 5-year epoch.

Study design is laudable

Caughey and colleagues did an admirable job of compiling data on nearly 10,000 CVS tests and 31,000 amniocentesis procedures and their associated clinical outcomes. The fact that this investigation was based at a single center with good follow-up is a definite strength. Also laudable is the attempt to control for background loss rate by adjusting for gestational age at the time of sampling in multivariable analysis, as well as the identification of a control group that underwent neither test.

The investigators also restrain themselves from extrapolating their conclusions or overstating their findings given the nonrandomized nature of the study.

Route of CVS was not specified

Unfortunately, we are not told whether the CVS procedures were performed transcervically, transabdominally, or using both approaches (as is common in many modern programs). Earlier reports involving transcervical sampling found a clear relationship between proximity of the placenta and cervix, as well as uterine position, and the risk of pregnancy loss.² That is one reason centers began to choose the sampling route based largely on placental location.^3,4 If the sampling route was individualized in this study, then the observations can be generalized to programs using a similar approach.

Other potential weaknesses (also cited by the authors) include limited demographic data among the entire population for habits or preconditions that might confound pregnancy loss, such as tobacco use and socioeconomic status. The mixture of experienced clinicians and trainees is another concern, although the authors claim they were equally distributed over the time frame.

More definitive answers are needed

Although this study will be useful in counseling patients who are considering invasive testing, it fails to answer the question of safety definitively. Such an answer requires randomization prior to CVS or the limiting of both procedures to the same gestational age range.

In the most recent head-to-head comparisons at similar gestational ages (11–14 weeks), CVS appears to be safer than amniocentesis.^5,6 The same cannot be said for testing later in the mid-trimester, when amniocentesis is usually performed and has a well-established track record for safety.

A Yes, according to this retrospective study, provided the practitioner has adequate training and experience. The authors analyzed 20 years of experience and found that the risk of pregnancy loss diminished over time for both test methods, but the reduction was more pronounced in women undergoing chorionic villus sampling (CVS). By the final epoch of study (1998–2003), there was no significant difference between the 2 methods.

Expert Commentary

Caughey and colleagues launched their study to explore the following questions: What is the rate of pregnancy loss in women who undergo CVS and amniocentesis, compared with those who do not? Has the higher rate of pregnancy loss associated with CVS changed over the past 20 years?

That invasive diagnostic procedures have a learning curve is no surprise.¹ It generally follows that the more efficient an operator becomes at a given invasive test, the lower the rate of complications. The clinical question facing us after this study is how valid the comparison is between the 2 procedures, even in the final 5-year epoch.

Study design is laudable

Caughey and colleagues did an admirable job of compiling data on nearly 10,000 CVS tests and 31,000 amniocentesis procedures and their associated clinical outcomes. The fact that this investigation was based at a single center with good follow-up is a definite strength. Also laudable is the attempt to control for background loss rate by adjusting for gestational age at the time of sampling in multivariable analysis, as well as the identification of a control group that underwent neither test.

The investigators also restrain themselves from extrapolating their conclusions or overstating their findings given the nonrandomized nature of the study.

Route of CVS was not specified

Unfortunately, we are not told whether the CVS procedures were performed transcervically, transabdominally, or using both approaches (as is common in many modern programs). Earlier reports involving transcervical sampling found a clear relationship between proximity of the placenta and cervix, as well as uterine position, and the risk of pregnancy loss.² That is one reason centers began to choose the sampling route based largely on placental location.^3,4 If the sampling route was individualized in this study, then the observations can be generalized to programs using a similar approach.

Other potential weaknesses (also cited by the authors) include limited demographic data among the entire population for habits or preconditions that might confound pregnancy loss, such as tobacco use and socioeconomic status. The mixture of experienced clinicians and trainees is another concern, although the authors claim they were equally distributed over the time frame.

More definitive answers are needed

Although this study will be useful in counseling patients who are considering invasive testing, it fails to answer the question of safety definitively. Such an answer requires randomization prior to CVS or the limiting of both procedures to the same gestational age range.

In the most recent head-to-head comparisons at similar gestational ages (11–14 weeks), CVS appears to be safer than amniocentesis.^5,6 The same cannot be said for testing later in the mid-trimester, when amniocentesis is usually performed and has a well-established track record for safety.

Like everything else, Pay for Performance (P4P) has inherent rewards and risks. For our patients, rewards include improved clinical care and outcomes, and for us, enhanced earnings. Among potential risks are a failure to earn higher compensation if we don’t participate in a voluntary P4P program, and/or finding our practices excluded from “preferred” status as more plans move toward tiered networks. P4P might be one way a plan decides which practices to include in a preferred network, advertising only practices that meet the “higher standards” of P4P.

Like it or not, P4P programs are already a reality for many of us, and their continued proliferation seems inevitable. This article describes the typical trajectory of a P4P program, the importance of being involved in program design as early as possible, and the challenges and successes of P4P thus far.

P4P goes a long way back

In 1986, Robert Fulgham wrote an insightful book entitled All I Really Need to Know I Learned in Kindergarten.¹ It’s hard to argue with the basic premise of that title. When I think back to my early school years, I remember well the reward for achievement: a gold star. And I was intent upon achieving my teacher’s goals. Why? For the gold star, of course. That was my first experience with P4P.

Let’s fast forward a few decades to focus on more sophisticated versions of the gold star, and consider what we need to know to be ready for P4P in our own practices.

5 critical questions

Although our involvement with P4P in health care has so far been limited, we are rapidly recognizing some of the challenges involved. Questions that must be answered include (but clearly are not limited to) the following:

Although a Robert Wood Johnson Foundation report issued in November 2005 concluded that P4P programs “can improve both medical care and quality of life by giving health-care providers a financial incentive to seek measurable improvements in the health of their patients,”² it may be too soon to make such a statement. According to a comprehensive and heavily documented article from the August 15 issue of Annals of Internal Medicine,³ “ongoing monitoring of incentive programs is critical to determine the effectiveness of financial incentives and their possible unintended effects on quality of care.”

Answers are on the way

We should soon be able to begin answering some of these questions, however. According to a major survey from 2005, the number of P4P programs in the United States more than tripled over the previous 2 to 3 years, totaling 115 in 2005,⁴ and it is very likely that the rate of increase will accelerate. The 2005 survey also disclosed some key findings, including the following:

Measures that overlap 2 specialties are not necessarily bad

Measuring “clinical improvement” or “quality” is particularly challenging. Outcomes are difficult to measure and influenced by many factors, only some of which are within our clinical control.

Should we use Health Plan Employer Data and Information Set (HEDIS) measures as a proxy for quality, such as rates of cervical or breast cancer screening? We must agree that it's good to screen for breast and cervical cancer. Unfortunately, many HEDIS measures fall into the no-man’s-land between obstetrics and gynecology and primary care—especially something like mammogram compliance.

 

As much as possible, we need to have input into program design, and should always suggest measures that fall more clearly within our domain, over which we have more control. However, measures that overlap 2 specialties are not necessarily bad. We will share the credit even if the primary-care physician (PCP) is the one who gets the patient to go for her mammogram—and the likelihood that the patient will be motivated to do so will be doubled, because both the PCP and the ObGyn will be recommending it.

We also need to recognize that P4P is already a certainty for many of us. That means someone is defining the measures by which we’ll be judged—and it might as well be us.

Private payers will have big impact

Although the Center for Medicare and Medicaid Services (CMS) is working with various physician groups and health organizations on several demonstration projects,⁵ its programs are complicated and not germane to many ObGyns at this time. We will see far greater impact on our practices from the private-payer P4P programs that are coming.

Most programs start simply

A typical privately sponsored P4P program usually starts off relatively simply and then, upon review (usually annually), is modified as the capabilities of both the sponsor and participants expand. One major insurer (a national payer) has a program that tracks several “process measures” (as opposed to “outcomes”). These include:

These are all HEDIS measures, and the plan itself is measured through them and other factors by the National Committee on Quality Assurance (NCQA). Accomplishing these goals is good not only for our patients (because they are undergoing appropriate screening), but also for the plan, whose NCQA ratings will improve as a result of improved HEDIS compliance.

The program also measures the extent to which a group adopts technology such as electronic medical records (EMRs), electronic health records, e-prescribing, and an electronic disease registry. This last item can be something as simple as a recall system within the larger practice-management system to ensure that patients with abnormal Pap tests, mammograms, and other lab studies are not lost to follow-up.

First, learn to walk

As in the example above, a program should start with several easy-to-measure indicators, such as processes that are either done or not done, whose performance can be tracked through administrative (billing) data. After some attention is focused on these indicators and as goals are reached, the indicators may continue to be monitored or be put aside for a variety of reasons. Gradually, other, more sophisticated measures will be introduced.

The program should mature as our experience grows and data systems improve so that, ultimately, we look at true indications that quality has improved—better outcomes, hopefully at a lower cost.

Emphasis on generic drugs will save dollars

For many plans, increases in generic pharmacy utilization will be rewarded. Now, the cynics among us might conclude that P4P is really all about saving money for the health plans. Remember, however, that most plans have tiered copays for prescriptions, and the patient herself will save a substantial amount in copays if you can prescribe a generic alternative—particularly in high-volume pharmaceutical areas.

Also realize that, if we want a P4P program to reward participants without taking away from those who don’t achieve their goals, the money has to come from somewhere. Savings generated from a successful pharmaceutical program can drive the P4P program and pay for more substantial rewards.

How your patients benefit from P4P

Assuming a program actually gets us to change our behavior in a positive way, it should result in improved quality of care. This entails obvious benefits for our patients, such as when we succeed in getting a woman to obtain a mammogram. Let’s say the P4P incentive to increase the rate of mammography leads us to change our office workflow and actually make the mammography appointment for the patient before she leaves our office. This may “cost” us a bit more staff time, but it will help us meet a goal that will increase our return from the P4P program and help the patient get a needed service.

We briefly touched on the reduced cost of generic drugs, which has the potential to save the payer incredible sums of money. But this reduction in cost has benefits for the patient, too, who may appreciate the lower out-of-pocket cost of generic drugs.

My experience: Better postpartum depression, chlamydia screening

Last year, one of our programs included a measure of postpartum depression screening. To meet the goal, we developed a brief worksheet that included the Edinburgh Depression Scale. This worksheet was distributed throughout the practice, and almost everyone used it at the postpartum visit. Our doctors and midwives were amazed at the number of cases of even mild to moderate depression that were discovered using this tool, and felt they had truly improved the quality of care by performing this screening more formally.

 

Chlamydia screening is another example. By implementing it in a more wholesale fashion, screening becomes easier to perform. Value judgments about a patient’s lifestyle are no longer necessary, and patients accept the screening as part of a larger program rather than as a by-product of their “high-risk” lifestyle.

The bottom line: If appropriate measures are included, we should be able to change clinical behavior and improve patient care.

Bonus could be bigger than you think

Rewards can be substantial in P4P programs. For example, they might consist of a bonus check delivered to the practice once or twice a year, or enhancement of the fee schedule by a certain percentage for the following year. The bonus check, too, may be based on a percentage calculated on top of total earnings from that payer during the time period measured. The precise enhancement possible is proprietary information for most plans, but generally ranges from 0% to high single digits.

That may not sound like much to you. But let’s assume you can earn up to 7%. Let’s also assume you have annual collections of $1 million in your practice and a particular payer is responsible for 25% of your revenues. That 7% would total an additional $17,500. If all your payers sponsored P4P programs and you did as well across the board, that would result in more than $70,000 in enhanced revenues—right to your bottom line.

Who’s looking out for ObGyns?

Many organizations are focusing on P4P, but the activities of the American College of Obstetricians and Gynecologists (ACOG) are most relevant. ACOG has been developing performance measures and plans to incorporate them into new practice bulletins. So far, 21 measures have been developed and are being beta-tested. Approximately 40 more measures are under consideration. The biggest problem to date: The data needed to evaluate performance are not readily available without chart review.⁶

How data are obtained is a rate-limiting step at this point—and perhaps always will be. Chart reviews are highly inefficient and costly, and often rely on extrapolation of results from a limited sample to the whole universe of charts. Sampling errors may be unavoidable.

Large groups may have a technology advantage if they can afford sophisticated practice-management systems—or even EMRs—that make it easier for them to prove compliance with a P4P program. Smaller groups would face increased costs for “mining” their own data manually, or find it necessary to rely on data developed by the P4P sponsor.

One of ACOG’s chief concerns (as well as that of other physician-friendly organizations) is design of a P4P program that can be easily implemented in any size practice.

EMR use remains limited

A recent article at www.amednews.com cites a 2003 survey showing that only about 25% of physicians have access to EMRs.⁷ A more recent article from Health Affairs puts that figure below 20% and identifies barriers to EMR implementation.⁸

The important point: Until we all use EMRs in our practices, P4P programs must be designed to work within the limitations of our data capabilities.

The Accreditation Association for Ambulatory Health Care’s (AAAHC) Institute for Quality Improvement has developed principles/guidelines for P4P (see www.aaahc.org), as has the AMA, with agreement in many of these areas.

Will anything bad happen if you do not participate?

In an age when “consumer-driven health care” and “transparency” are becoming everyday mantras, a practice must stay ahead of the curve as much as possible and not be left on the platform as the train pulls away. Make no mistake, part of the P4P rewards system in the future will be public recognition, which will help payers drive their members to the “better” doctors. A refusal to participate in a P4P program might initiate a downward spiral from which it may be difficult to recover.

I don’t mean to imply that the move to consumer-driven health care is necessarily a bad thing. After all, ObGyns are frequently chosen by patients on the basis of word-of-mouth recommendations. I’m simply saying that, if data about us are going to be available for members to peruse prior to their selection of a provider, we should try to control that data as much as possible. It is vitally important that measures used to qualify us as “high performers” are, first of all, meaningful and, just as important, accurate.

A major risk is that a focus on process goals interferes with our attention to outcomes. What good is it if every patient undergoes cervical cancer screening if we don’t properly triage abnormal results? P4P should not distract us from what should be our raison d’être: giving the best quality care we can, leading to the best outcomes.

 

How can we prepare?

And remember, at least in theory, P4P makes sense. If we can accurately measure quality and fairly identify higher-quality providers, we can reward them appropriately. If it is possible to improve quality by driving more providers to meet higher standards, then the program is worthwhile.

Most of us feel that we are at least among “the best” in our practice market area. Here is an opportunity to prove it and earn that gold star!

The author reports no financial relationships relevant to this article.

Like everything else, Pay for Performance (P4P) has inherent rewards and risks. For our patients, rewards include improved clinical care and outcomes, and for us, enhanced earnings. Among potential risks are a failure to earn higher compensation if we don’t participate in a voluntary P4P program, and/or finding our practices excluded from “preferred” status as more plans move toward tiered networks. P4P might be one way a plan decides which practices to include in a preferred network, advertising only practices that meet the “higher standards” of P4P.

Like it or not, P4P programs are already a reality for many of us, and their continued proliferation seems inevitable. This article describes the typical trajectory of a P4P program, the importance of being involved in program design as early as possible, and the challenges and successes of P4P thus far.

P4P goes a long way back

In 1986, Robert Fulgham wrote an insightful book entitled All I Really Need to Know I Learned in Kindergarten.¹ It’s hard to argue with the basic premise of that title. When I think back to my early school years, I remember well the reward for achievement: a gold star. And I was intent upon achieving my teacher’s goals. Why? For the gold star, of course. That was my first experience with P4P.

Let’s fast forward a few decades to focus on more sophisticated versions of the gold star, and consider what we need to know to be ready for P4P in our own practices.

5 critical questions

Although our involvement with P4P in health care has so far been limited, we are rapidly recognizing some of the challenges involved. Questions that must be answered include (but clearly are not limited to) the following:

Although a Robert Wood Johnson Foundation report issued in November 2005 concluded that P4P programs “can improve both medical care and quality of life by giving health-care providers a financial incentive to seek measurable improvements in the health of their patients,”² it may be too soon to make such a statement. According to a comprehensive and heavily documented article from the August 15 issue of Annals of Internal Medicine,³ “ongoing monitoring of incentive programs is critical to determine the effectiveness of financial incentives and their possible unintended effects on quality of care.”

Answers are on the way

We should soon be able to begin answering some of these questions, however. According to a major survey from 2005, the number of P4P programs in the United States more than tripled over the previous 2 to 3 years, totaling 115 in 2005,⁴ and it is very likely that the rate of increase will accelerate. The 2005 survey also disclosed some key findings, including the following:

Measures that overlap 2 specialties are not necessarily bad

Measuring “clinical improvement” or “quality” is particularly challenging. Outcomes are difficult to measure and influenced by many factors, only some of which are within our clinical control.

Should we use Health Plan Employer Data and Information Set (HEDIS) measures as a proxy for quality, such as rates of cervical or breast cancer screening? We must agree that it's good to screen for breast and cervical cancer. Unfortunately, many HEDIS measures fall into the no-man’s-land between obstetrics and gynecology and primary care—especially something like mammogram compliance.

 

As much as possible, we need to have input into program design, and should always suggest measures that fall more clearly within our domain, over which we have more control. However, measures that overlap 2 specialties are not necessarily bad. We will share the credit even if the primary-care physician (PCP) is the one who gets the patient to go for her mammogram—and the likelihood that the patient will be motivated to do so will be doubled, because both the PCP and the ObGyn will be recommending it.

We also need to recognize that P4P is already a certainty for many of us. That means someone is defining the measures by which we’ll be judged—and it might as well be us.

Private payers will have big impact

Although the Center for Medicare and Medicaid Services (CMS) is working with various physician groups and health organizations on several demonstration projects,⁵ its programs are complicated and not germane to many ObGyns at this time. We will see far greater impact on our practices from the private-payer P4P programs that are coming.

Most programs start simply

A typical privately sponsored P4P program usually starts off relatively simply and then, upon review (usually annually), is modified as the capabilities of both the sponsor and participants expand. One major insurer (a national payer) has a program that tracks several “process measures” (as opposed to “outcomes”). These include:

These are all HEDIS measures, and the plan itself is measured through them and other factors by the National Committee on Quality Assurance (NCQA). Accomplishing these goals is good not only for our patients (because they are undergoing appropriate screening), but also for the plan, whose NCQA ratings will improve as a result of improved HEDIS compliance.

The program also measures the extent to which a group adopts technology such as electronic medical records (EMRs), electronic health records, e-prescribing, and an electronic disease registry. This last item can be something as simple as a recall system within the larger practice-management system to ensure that patients with abnormal Pap tests, mammograms, and other lab studies are not lost to follow-up.

First, learn to walk

As in the example above, a program should start with several easy-to-measure indicators, such as processes that are either done or not done, whose performance can be tracked through administrative (billing) data. After some attention is focused on these indicators and as goals are reached, the indicators may continue to be monitored or be put aside for a variety of reasons. Gradually, other, more sophisticated measures will be introduced.

The program should mature as our experience grows and data systems improve so that, ultimately, we look at true indications that quality has improved—better outcomes, hopefully at a lower cost.

Emphasis on generic drugs will save dollars

For many plans, increases in generic pharmacy utilization will be rewarded. Now, the cynics among us might conclude that P4P is really all about saving money for the health plans. Remember, however, that most plans have tiered copays for prescriptions, and the patient herself will save a substantial amount in copays if you can prescribe a generic alternative—particularly in high-volume pharmaceutical areas.

Also realize that, if we want a P4P program to reward participants without taking away from those who don’t achieve their goals, the money has to come from somewhere. Savings generated from a successful pharmaceutical program can drive the P4P program and pay for more substantial rewards.

How your patients benefit from P4P

Assuming a program actually gets us to change our behavior in a positive way, it should result in improved quality of care. This entails obvious benefits for our patients, such as when we succeed in getting a woman to obtain a mammogram. Let’s say the P4P incentive to increase the rate of mammography leads us to change our office workflow and actually make the mammography appointment for the patient before she leaves our office. This may “cost” us a bit more staff time, but it will help us meet a goal that will increase our return from the P4P program and help the patient get a needed service.

We briefly touched on the reduced cost of generic drugs, which has the potential to save the payer incredible sums of money. But this reduction in cost has benefits for the patient, too, who may appreciate the lower out-of-pocket cost of generic drugs.

My experience: Better postpartum depression, chlamydia screening

Last year, one of our programs included a measure of postpartum depression screening. To meet the goal, we developed a brief worksheet that included the Edinburgh Depression Scale. This worksheet was distributed throughout the practice, and almost everyone used it at the postpartum visit. Our doctors and midwives were amazed at the number of cases of even mild to moderate depression that were discovered using this tool, and felt they had truly improved the quality of care by performing this screening more formally.

 

Chlamydia screening is another example. By implementing it in a more wholesale fashion, screening becomes easier to perform. Value judgments about a patient’s lifestyle are no longer necessary, and patients accept the screening as part of a larger program rather than as a by-product of their “high-risk” lifestyle.

The bottom line: If appropriate measures are included, we should be able to change clinical behavior and improve patient care.

Bonus could be bigger than you think

Rewards can be substantial in P4P programs. For example, they might consist of a bonus check delivered to the practice once or twice a year, or enhancement of the fee schedule by a certain percentage for the following year. The bonus check, too, may be based on a percentage calculated on top of total earnings from that payer during the time period measured. The precise enhancement possible is proprietary information for most plans, but generally ranges from 0% to high single digits.

That may not sound like much to you. But let’s assume you can earn up to 7%. Let’s also assume you have annual collections of $1 million in your practice and a particular payer is responsible for 25% of your revenues. That 7% would total an additional $17,500. If all your payers sponsored P4P programs and you did as well across the board, that would result in more than $70,000 in enhanced revenues—right to your bottom line.

Who’s looking out for ObGyns?

Many organizations are focusing on P4P, but the activities of the American College of Obstetricians and Gynecologists (ACOG) are most relevant. ACOG has been developing performance measures and plans to incorporate them into new practice bulletins. So far, 21 measures have been developed and are being beta-tested. Approximately 40 more measures are under consideration. The biggest problem to date: The data needed to evaluate performance are not readily available without chart review.⁶

How data are obtained is a rate-limiting step at this point—and perhaps always will be. Chart reviews are highly inefficient and costly, and often rely on extrapolation of results from a limited sample to the whole universe of charts. Sampling errors may be unavoidable.

Large groups may have a technology advantage if they can afford sophisticated practice-management systems—or even EMRs—that make it easier for them to prove compliance with a P4P program. Smaller groups would face increased costs for “mining” their own data manually, or find it necessary to rely on data developed by the P4P sponsor.

One of ACOG’s chief concerns (as well as that of other physician-friendly organizations) is design of a P4P program that can be easily implemented in any size practice.

EMR use remains limited

A recent article at www.amednews.com cites a 2003 survey showing that only about 25% of physicians have access to EMRs.⁷ A more recent article from Health Affairs puts that figure below 20% and identifies barriers to EMR implementation.⁸

The important point: Until we all use EMRs in our practices, P4P programs must be designed to work within the limitations of our data capabilities.

The Accreditation Association for Ambulatory Health Care’s (AAAHC) Institute for Quality Improvement has developed principles/guidelines for P4P (see www.aaahc.org), as has the AMA, with agreement in many of these areas.

Will anything bad happen if you do not participate?

In an age when “consumer-driven health care” and “transparency” are becoming everyday mantras, a practice must stay ahead of the curve as much as possible and not be left on the platform as the train pulls away. Make no mistake, part of the P4P rewards system in the future will be public recognition, which will help payers drive their members to the “better” doctors. A refusal to participate in a P4P program might initiate a downward spiral from which it may be difficult to recover.

I don’t mean to imply that the move to consumer-driven health care is necessarily a bad thing. After all, ObGyns are frequently chosen by patients on the basis of word-of-mouth recommendations. I’m simply saying that, if data about us are going to be available for members to peruse prior to their selection of a provider, we should try to control that data as much as possible. It is vitally important that measures used to qualify us as “high performers” are, first of all, meaningful and, just as important, accurate.

A major risk is that a focus on process goals interferes with our attention to outcomes. What good is it if every patient undergoes cervical cancer screening if we don’t properly triage abnormal results? P4P should not distract us from what should be our raison d’être: giving the best quality care we can, leading to the best outcomes.

 

How can we prepare?

And remember, at least in theory, P4P makes sense. If we can accurately measure quality and fairly identify higher-quality providers, we can reward them appropriately. If it is possible to improve quality by driving more providers to meet higher standards, then the program is worthwhile.

Most of us feel that we are at least among “the best” in our practice market area. Here is an opportunity to prove it and earn that gold star!

The author reports no financial relationships relevant to this article.

Like everything else, Pay for Performance (P4P) has inherent rewards and risks. For our patients, rewards include improved clinical care and outcomes, and for us, enhanced earnings. Among potential risks are a failure to earn higher compensation if we don’t participate in a voluntary P4P program, and/or finding our practices excluded from “preferred” status as more plans move toward tiered networks. P4P might be one way a plan decides which practices to include in a preferred network, advertising only practices that meet the “higher standards” of P4P.

Like it or not, P4P programs are already a reality for many of us, and their continued proliferation seems inevitable. This article describes the typical trajectory of a P4P program, the importance of being involved in program design as early as possible, and the challenges and successes of P4P thus far.

P4P goes a long way back

In 1986, Robert Fulgham wrote an insightful book entitled All I Really Need to Know I Learned in Kindergarten.¹ It’s hard to argue with the basic premise of that title. When I think back to my early school years, I remember well the reward for achievement: a gold star. And I was intent upon achieving my teacher’s goals. Why? For the gold star, of course. That was my first experience with P4P.

Let’s fast forward a few decades to focus on more sophisticated versions of the gold star, and consider what we need to know to be ready for P4P in our own practices.

5 critical questions

Although our involvement with P4P in health care has so far been limited, we are rapidly recognizing some of the challenges involved. Questions that must be answered include (but clearly are not limited to) the following:

Although a Robert Wood Johnson Foundation report issued in November 2005 concluded that P4P programs “can improve both medical care and quality of life by giving health-care providers a financial incentive to seek measurable improvements in the health of their patients,”² it may be too soon to make such a statement. According to a comprehensive and heavily documented article from the August 15 issue of Annals of Internal Medicine,³ “ongoing monitoring of incentive programs is critical to determine the effectiveness of financial incentives and their possible unintended effects on quality of care.”

Answers are on the way

We should soon be able to begin answering some of these questions, however. According to a major survey from 2005, the number of P4P programs in the United States more than tripled over the previous 2 to 3 years, totaling 115 in 2005,⁴ and it is very likely that the rate of increase will accelerate. The 2005 survey also disclosed some key findings, including the following:

Measures that overlap 2 specialties are not necessarily bad

Measuring “clinical improvement” or “quality” is particularly challenging. Outcomes are difficult to measure and influenced by many factors, only some of which are within our clinical control.

Should we use Health Plan Employer Data and Information Set (HEDIS) measures as a proxy for quality, such as rates of cervical or breast cancer screening? We must agree that it's good to screen for breast and cervical cancer. Unfortunately, many HEDIS measures fall into the no-man’s-land between obstetrics and gynecology and primary care—especially something like mammogram compliance.

 

As much as possible, we need to have input into program design, and should always suggest measures that fall more clearly within our domain, over which we have more control. However, measures that overlap 2 specialties are not necessarily bad. We will share the credit even if the primary-care physician (PCP) is the one who gets the patient to go for her mammogram—and the likelihood that the patient will be motivated to do so will be doubled, because both the PCP and the ObGyn will be recommending it.

We also need to recognize that P4P is already a certainty for many of us. That means someone is defining the measures by which we’ll be judged—and it might as well be us.

Private payers will have big impact

Although the Center for Medicare and Medicaid Services (CMS) is working with various physician groups and health organizations on several demonstration projects,⁵ its programs are complicated and not germane to many ObGyns at this time. We will see far greater impact on our practices from the private-payer P4P programs that are coming.

Most programs start simply

A typical privately sponsored P4P program usually starts off relatively simply and then, upon review (usually annually), is modified as the capabilities of both the sponsor and participants expand. One major insurer (a national payer) has a program that tracks several “process measures” (as opposed to “outcomes”). These include:

These are all HEDIS measures, and the plan itself is measured through them and other factors by the National Committee on Quality Assurance (NCQA). Accomplishing these goals is good not only for our patients (because they are undergoing appropriate screening), but also for the plan, whose NCQA ratings will improve as a result of improved HEDIS compliance.

The program also measures the extent to which a group adopts technology such as electronic medical records (EMRs), electronic health records, e-prescribing, and an electronic disease registry. This last item can be something as simple as a recall system within the larger practice-management system to ensure that patients with abnormal Pap tests, mammograms, and other lab studies are not lost to follow-up.

First, learn to walk

As in the example above, a program should start with several easy-to-measure indicators, such as processes that are either done or not done, whose performance can be tracked through administrative (billing) data. After some attention is focused on these indicators and as goals are reached, the indicators may continue to be monitored or be put aside for a variety of reasons. Gradually, other, more sophisticated measures will be introduced.

The program should mature as our experience grows and data systems improve so that, ultimately, we look at true indications that quality has improved—better outcomes, hopefully at a lower cost.

Emphasis on generic drugs will save dollars

For many plans, increases in generic pharmacy utilization will be rewarded. Now, the cynics among us might conclude that P4P is really all about saving money for the health plans. Remember, however, that most plans have tiered copays for prescriptions, and the patient herself will save a substantial amount in copays if you can prescribe a generic alternative—particularly in high-volume pharmaceutical areas.

Also realize that, if we want a P4P program to reward participants without taking away from those who don’t achieve their goals, the money has to come from somewhere. Savings generated from a successful pharmaceutical program can drive the P4P program and pay for more substantial rewards.

How your patients benefit from P4P

Assuming a program actually gets us to change our behavior in a positive way, it should result in improved quality of care. This entails obvious benefits for our patients, such as when we succeed in getting a woman to obtain a mammogram. Let’s say the P4P incentive to increase the rate of mammography leads us to change our office workflow and actually make the mammography appointment for the patient before she leaves our office. This may “cost” us a bit more staff time, but it will help us meet a goal that will increase our return from the P4P program and help the patient get a needed service.

We briefly touched on the reduced cost of generic drugs, which has the potential to save the payer incredible sums of money. But this reduction in cost has benefits for the patient, too, who may appreciate the lower out-of-pocket cost of generic drugs.

My experience: Better postpartum depression, chlamydia screening

Last year, one of our programs included a measure of postpartum depression screening. To meet the goal, we developed a brief worksheet that included the Edinburgh Depression Scale. This worksheet was distributed throughout the practice, and almost everyone used it at the postpartum visit. Our doctors and midwives were amazed at the number of cases of even mild to moderate depression that were discovered using this tool, and felt they had truly improved the quality of care by performing this screening more formally.

 

Chlamydia screening is another example. By implementing it in a more wholesale fashion, screening becomes easier to perform. Value judgments about a patient’s lifestyle are no longer necessary, and patients accept the screening as part of a larger program rather than as a by-product of their “high-risk” lifestyle.

The bottom line: If appropriate measures are included, we should be able to change clinical behavior and improve patient care.

Bonus could be bigger than you think

Rewards can be substantial in P4P programs. For example, they might consist of a bonus check delivered to the practice once or twice a year, or enhancement of the fee schedule by a certain percentage for the following year. The bonus check, too, may be based on a percentage calculated on top of total earnings from that payer during the time period measured. The precise enhancement possible is proprietary information for most plans, but generally ranges from 0% to high single digits.

That may not sound like much to you. But let’s assume you can earn up to 7%. Let’s also assume you have annual collections of $1 million in your practice and a particular payer is responsible for 25% of your revenues. That 7% would total an additional $17,500. If all your payers sponsored P4P programs and you did as well across the board, that would result in more than $70,000 in enhanced revenues—right to your bottom line.

Who’s looking out for ObGyns?

Many organizations are focusing on P4P, but the activities of the American College of Obstetricians and Gynecologists (ACOG) are most relevant. ACOG has been developing performance measures and plans to incorporate them into new practice bulletins. So far, 21 measures have been developed and are being beta-tested. Approximately 40 more measures are under consideration. The biggest problem to date: The data needed to evaluate performance are not readily available without chart review.⁶

How data are obtained is a rate-limiting step at this point—and perhaps always will be. Chart reviews are highly inefficient and costly, and often rely on extrapolation of results from a limited sample to the whole universe of charts. Sampling errors may be unavoidable.

Large groups may have a technology advantage if they can afford sophisticated practice-management systems—or even EMRs—that make it easier for them to prove compliance with a P4P program. Smaller groups would face increased costs for “mining” their own data manually, or find it necessary to rely on data developed by the P4P sponsor.

One of ACOG’s chief concerns (as well as that of other physician-friendly organizations) is design of a P4P program that can be easily implemented in any size practice.

EMR use remains limited

A recent article at www.amednews.com cites a 2003 survey showing that only about 25% of physicians have access to EMRs.⁷ A more recent article from Health Affairs puts that figure below 20% and identifies barriers to EMR implementation.⁸

The important point: Until we all use EMRs in our practices, P4P programs must be designed to work within the limitations of our data capabilities.

The Accreditation Association for Ambulatory Health Care’s (AAAHC) Institute for Quality Improvement has developed principles/guidelines for P4P (see www.aaahc.org), as has the AMA, with agreement in many of these areas.

Will anything bad happen if you do not participate?

In an age when “consumer-driven health care” and “transparency” are becoming everyday mantras, a practice must stay ahead of the curve as much as possible and not be left on the platform as the train pulls away. Make no mistake, part of the P4P rewards system in the future will be public recognition, which will help payers drive their members to the “better” doctors. A refusal to participate in a P4P program might initiate a downward spiral from which it may be difficult to recover.

I don’t mean to imply that the move to consumer-driven health care is necessarily a bad thing. After all, ObGyns are frequently chosen by patients on the basis of word-of-mouth recommendations. I’m simply saying that, if data about us are going to be available for members to peruse prior to their selection of a provider, we should try to control that data as much as possible. It is vitally important that measures used to qualify us as “high performers” are, first of all, meaningful and, just as important, accurate.

A major risk is that a focus on process goals interferes with our attention to outcomes. What good is it if every patient undergoes cervical cancer screening if we don’t properly triage abnormal results? P4P should not distract us from what should be our raison d’être: giving the best quality care we can, leading to the best outcomes.

 

How can we prepare?

And remember, at least in theory, P4P makes sense. If we can accurately measure quality and fairly identify higher-quality providers, we can reward them appropriately. If it is possible to improve quality by driving more providers to meet higher standards, then the program is worthwhile.

Most of us feel that we are at least among “the best” in our practice market area. Here is an opportunity to prove it and earn that gold star!

The author reports no financial relationships relevant to this article.

THE ROAD AHEAD

This new series in Obg Management will keep you up to date on the many changes expected to take place as a result of the 2006 Consensus Conference held in September, and the introduction of HPV vaccines.

Our whole approach to cervical cancer prevention is likely to change within the next few years. Today, many obstetricians and gynecologists still consider the annual Papanicolaou test “the gold standard.” This is going to change, however, with…

ObGyns nationwide follow guidelines

This article summarizes the September 2006 Consensus Conference, organized by the ASCCP. The goal was to keep pace with the explosion of new data from clinical trials published in the last 5 years. The expected release date for the 2006 Guidelines is in the Spring or Summer of 2007. The 2001 Consensus Guidelines for the Management of Women With Cytologic Abnormalities have been extremely successful—they are now utilized by most clinicians and managed care organizations nationwide. In the last 5 years alone, more than 500,000 copies of the management algorithms have been downloaded from the ASCCP’s Web site (http://www.asccp.org), and many more have been downloaded from the Journal of the American Medical Association and the national guideline clearinghouse.

In large part, this success derived from the fact that most professional societies and federal agencies that deal with cervical cancer screening partnered in their development. Although the ASCCP organized the effort, 29 professional organizations participated. This meant that when groups such as ACOG subsequently developed guidelines for their members, they closely mirrored the 2001 Consensus Guidelines.

The 2006 Consensus Conference included approximately 100 delegates, 28 national and international professional societies, and federal agencies, but the meeting itself was only the final step in a long process. For 18 months, 6 different working groups reviewed the literature and determined where changes were needed.

NEW GUIDELINES ARE EVIDENCE-BASED

“The working groups evaluated hundreds of manuscripts and studies to make certain that the new guidelines remain evidence-based”

Kathy Poole, ASCCP Executive Director

The working groups posted their findings on Internet-based bulletin boards that allowed anyone in the national or international screening community to have input.

NEW GUIDELINES ARE SIMPLER

“One of the key goals of the 2006 Guidelines is simplification”

Dr. Mark Spitzer, ASCCP President and Chairman, Department of Obstetrics and Gynecology, Brookdale University Hospital and Medical Center, Brooklyn

“Many clinicians who manage women with cytologic abnormalities are not obstetricians and gynecologists. Nurse practitioners and family practice clinicians who don’t spend their entire lives dealing with abnormal Pap smears are responsible for much of the cervical cancer screening that takes place nationally,” said Dr. Spitzer. “The 2001 Consensus Guidelines have sometimes been characterized as complex and difficult to follow by such clinicians.”

Atypical squamous cells

HPV DNA-positive ASC-US vs LSIL

No major changes were recommended for the general population with ASC-US. However, since the ALTS trial clearly demonstrated that women with ASC-US who are high-risk HPV DNA-positive are essentially identical to women with LSIL, an effort was made to ensure that recommendations for these 2 groups are identical.

IDENTICAL MANAGEMENT

“Current data clearly indicate that women with ASC-US who are HPV DNA-positive and women with LSIL have the same risk of having high-grade disease and should therefore be managed identically” Dr. Spitzer

Although new data resulted in a number of minor changes to ASC-US recommendations, there are more significant changes in management of ASC-US with “special circumstances.” The 2001 Guidelines identified postmenopausal women and immuno-suppressed women with ASC-US as “special circumstances” to be managed differently than the general population. New guidelines eliminate this distinction.

Limited colposcopy in adolescents

Previously there was no provision for managing adolescents (up to 20 years of age) with ASC-US differently than the general population. New guidelines add adolescents as a “special population,” with different management. This change is based on considerable data demonstrating that the risk of cervical cancer is extremely low in adolescents, and that more than two thirds of adolescents with ASC-US are referred to colposcopy if “reflex” HPV DNA testing or repeat cervical cytology is utilized. Based on the newer data, a more conservative approach, which greatly limits use of colposcopy, will be introduced.

ASC-H

A number of studies have confirmed a high prevalence of CIN 2,3 as well as a high prevalence of high-risk HPV DNA positivity in women with ASC-H compared with women with ASC-US. Therefore, no substantive changes were made in the management recommendations for ASC-H. However, the need for a complete review of cytology, colposcopy, and histology results is downplayed for ASC-H without high-grade CIN.

 

LSIL and CIN 1

Basic management did not change for the general population, but did change for adolescents and postmenopausal women:

Previously, management of CIN 1 depended on whether colposcopy was satisfactory. Either treatment or follow-up was acceptable for women with CIN 1 and satisfactory colposcopy, but a diagnostic excisional procedure was advised for unsatisfactory colposcopy.

This has changed. The importance of a satisfactory colposcopic examination is deemphasized, and conservative follow-up of CIN 1 (which really represents histological manifestations of a productive HPV infection rather than a cancer precursor) is now stressed. Treatment for CIN 1 is particularly discouraged among adolescents.

HSIL and CIN 2,3

Immediate “screen and treat” as a management strategy for HSIL in the general population is emphasized more. As with ASC-H, the need for a complete review of the cytology, colposcopy, and histology results for women with HSIL in whom CIN 2,3 is not identified is deemphasized.

New guidelines no longer require that women with HSIL who do not have biopsy-confirmed CIN 2,3 undergo a diagnostic excisional procedure.

Basic management of CIN 2,3 is modified in only minor ways; however, options for conservative management of adolescents with CIN 2,3 are expanded (as for other clinical scenarios such as ASC-US, LSIL, and HSIL in adolescents).

Atypical glandular cells

HPV DNA STATUS MATTERS

“Based on data obtained since the 2001 Consensus Conference, it now appears reasonable to incorporate knowledge of a woman’s HPV status in management of atypical glandular cell (AGC) cytological abnormalities”

Dr. Charles Dunton, Chair, AGC Working Group, and Director, Division of Gynecological Oncology, Albert Einstein Medical Center, Wynnewood, Pa

Although the 2001 recommendation that almost all women with AGC undergo colposcopy remains, recommended follow-up will be modified to take into account HPV DNA status. Women who are high-risk HPV DNA-negative can be followed less aggressively than those who are high-risk HPV DNA-positive.

Other new guidelines

These include specific guidelines for managing benign endometrial cells identified during routine cytology (in both postmenopausal and cycling women) and benign-appearing glandular cells identified on routine cytology in women who have had a hysterectomy, as well as comprehensive management recommendations for women with biopsy-confirmed cervical adenocarcinoma in situ.

HPV DNA testing

“The 2001 guidelines did not address HPV DNA testing as an adjunct to cervical cytology in women aged 30 and older because HPV DNA testing was not yet FDA approved for this use,” says Dr. Edward J. Wilkinson, Chair, HPV DNA Working Group, and Professor and Vice Chairman, Department of Pathology, University of Florida College of Medicine, Gainesville. Therefore, the Interim Guidance introduced by the ASCCP/NCI/ACS in 2004 was the basis for new recommendations. For the most part, the 2006 Consensus Conference formally adopted the Interim Guidance published in 2004.

Quite a bit of consideration was given to how management will change once the FDA approves genotyping assays that identify HPV 16 and 18 for clinical use. Once such assays become available, the new guidelines indicate that there is sufficient data to support the triage of women who are cytology-negative/HPV DNA-positive, using HPV genotyping assays that identify HPV 16 and 18.

THE ROAD AHEAD

This new series in Obg Management will keep you up to date on the many changes expected to take place as a result of the 2006 Consensus Conference held in September, and the introduction of HPV vaccines.

Our whole approach to cervical cancer prevention is likely to change within the next few years. Today, many obstetricians and gynecologists still consider the annual Papanicolaou test “the gold standard.” This is going to change, however, with…

ObGyns nationwide follow guidelines

This article summarizes the September 2006 Consensus Conference, organized by the ASCCP. The goal was to keep pace with the explosion of new data from clinical trials published in the last 5 years. The expected release date for the 2006 Guidelines is in the Spring or Summer of 2007. The 2001 Consensus Guidelines for the Management of Women With Cytologic Abnormalities have been extremely successful—they are now utilized by most clinicians and managed care organizations nationwide. In the last 5 years alone, more than 500,000 copies of the management algorithms have been downloaded from the ASCCP’s Web site (http://www.asccp.org), and many more have been downloaded from the Journal of the American Medical Association and the national guideline clearinghouse.

In large part, this success derived from the fact that most professional societies and federal agencies that deal with cervical cancer screening partnered in their development. Although the ASCCP organized the effort, 29 professional organizations participated. This meant that when groups such as ACOG subsequently developed guidelines for their members, they closely mirrored the 2001 Consensus Guidelines.

The 2006 Consensus Conference included approximately 100 delegates, 28 national and international professional societies, and federal agencies, but the meeting itself was only the final step in a long process. For 18 months, 6 different working groups reviewed the literature and determined where changes were needed.

NEW GUIDELINES ARE EVIDENCE-BASED

“The working groups evaluated hundreds of manuscripts and studies to make certain that the new guidelines remain evidence-based”

Kathy Poole, ASCCP Executive Director

The working groups posted their findings on Internet-based bulletin boards that allowed anyone in the national or international screening community to have input.

NEW GUIDELINES ARE SIMPLER

“One of the key goals of the 2006 Guidelines is simplification”

Dr. Mark Spitzer, ASCCP President and Chairman, Department of Obstetrics and Gynecology, Brookdale University Hospital and Medical Center, Brooklyn

“Many clinicians who manage women with cytologic abnormalities are not obstetricians and gynecologists. Nurse practitioners and family practice clinicians who don’t spend their entire lives dealing with abnormal Pap smears are responsible for much of the cervical cancer screening that takes place nationally,” said Dr. Spitzer. “The 2001 Consensus Guidelines have sometimes been characterized as complex and difficult to follow by such clinicians.”

Atypical squamous cells

HPV DNA-positive ASC-US vs LSIL

No major changes were recommended for the general population with ASC-US. However, since the ALTS trial clearly demonstrated that women with ASC-US who are high-risk HPV DNA-positive are essentially identical to women with LSIL, an effort was made to ensure that recommendations for these 2 groups are identical.

IDENTICAL MANAGEMENT

“Current data clearly indicate that women with ASC-US who are HPV DNA-positive and women with LSIL have the same risk of having high-grade disease and should therefore be managed identically” Dr. Spitzer

Although new data resulted in a number of minor changes to ASC-US recommendations, there are more significant changes in management of ASC-US with “special circumstances.” The 2001 Guidelines identified postmenopausal women and immuno-suppressed women with ASC-US as “special circumstances” to be managed differently than the general population. New guidelines eliminate this distinction.

Limited colposcopy in adolescents

Previously there was no provision for managing adolescents (up to 20 years of age) with ASC-US differently than the general population. New guidelines add adolescents as a “special population,” with different management. This change is based on considerable data demonstrating that the risk of cervical cancer is extremely low in adolescents, and that more than two thirds of adolescents with ASC-US are referred to colposcopy if “reflex” HPV DNA testing or repeat cervical cytology is utilized. Based on the newer data, a more conservative approach, which greatly limits use of colposcopy, will be introduced.

ASC-H

A number of studies have confirmed a high prevalence of CIN 2,3 as well as a high prevalence of high-risk HPV DNA positivity in women with ASC-H compared with women with ASC-US. Therefore, no substantive changes were made in the management recommendations for ASC-H. However, the need for a complete review of cytology, colposcopy, and histology results is downplayed for ASC-H without high-grade CIN.

 

LSIL and CIN 1

Basic management did not change for the general population, but did change for adolescents and postmenopausal women:

Previously, management of CIN 1 depended on whether colposcopy was satisfactory. Either treatment or follow-up was acceptable for women with CIN 1 and satisfactory colposcopy, but a diagnostic excisional procedure was advised for unsatisfactory colposcopy.

This has changed. The importance of a satisfactory colposcopic examination is deemphasized, and conservative follow-up of CIN 1 (which really represents histological manifestations of a productive HPV infection rather than a cancer precursor) is now stressed. Treatment for CIN 1 is particularly discouraged among adolescents.

HSIL and CIN 2,3

Immediate “screen and treat” as a management strategy for HSIL in the general population is emphasized more. As with ASC-H, the need for a complete review of the cytology, colposcopy, and histology results for women with HSIL in whom CIN 2,3 is not identified is deemphasized.

New guidelines no longer require that women with HSIL who do not have biopsy-confirmed CIN 2,3 undergo a diagnostic excisional procedure.

Basic management of CIN 2,3 is modified in only minor ways; however, options for conservative management of adolescents with CIN 2,3 are expanded (as for other clinical scenarios such as ASC-US, LSIL, and HSIL in adolescents).

Atypical glandular cells

HPV DNA STATUS MATTERS

“Based on data obtained since the 2001 Consensus Conference, it now appears reasonable to incorporate knowledge of a woman’s HPV status in management of atypical glandular cell (AGC) cytological abnormalities”

Dr. Charles Dunton, Chair, AGC Working Group, and Director, Division of Gynecological Oncology, Albert Einstein Medical Center, Wynnewood, Pa

Although the 2001 recommendation that almost all women with AGC undergo colposcopy remains, recommended follow-up will be modified to take into account HPV DNA status. Women who are high-risk HPV DNA-negative can be followed less aggressively than those who are high-risk HPV DNA-positive.

Other new guidelines

These include specific guidelines for managing benign endometrial cells identified during routine cytology (in both postmenopausal and cycling women) and benign-appearing glandular cells identified on routine cytology in women who have had a hysterectomy, as well as comprehensive management recommendations for women with biopsy-confirmed cervical adenocarcinoma in situ.

HPV DNA testing

“The 2001 guidelines did not address HPV DNA testing as an adjunct to cervical cytology in women aged 30 and older because HPV DNA testing was not yet FDA approved for this use,” says Dr. Edward J. Wilkinson, Chair, HPV DNA Working Group, and Professor and Vice Chairman, Department of Pathology, University of Florida College of Medicine, Gainesville. Therefore, the Interim Guidance introduced by the ASCCP/NCI/ACS in 2004 was the basis for new recommendations. For the most part, the 2006 Consensus Conference formally adopted the Interim Guidance published in 2004.

Quite a bit of consideration was given to how management will change once the FDA approves genotyping assays that identify HPV 16 and 18 for clinical use. Once such assays become available, the new guidelines indicate that there is sufficient data to support the triage of women who are cytology-negative/HPV DNA-positive, using HPV genotyping assays that identify HPV 16 and 18.

THE ROAD AHEAD

This new series in Obg Management will keep you up to date on the many changes expected to take place as a result of the 2006 Consensus Conference held in September, and the introduction of HPV vaccines.

Our whole approach to cervical cancer prevention is likely to change within the next few years. Today, many obstetricians and gynecologists still consider the annual Papanicolaou test “the gold standard.” This is going to change, however, with…

ObGyns nationwide follow guidelines

This article summarizes the September 2006 Consensus Conference, organized by the ASCCP. The goal was to keep pace with the explosion of new data from clinical trials published in the last 5 years. The expected release date for the 2006 Guidelines is in the Spring or Summer of 2007. The 2001 Consensus Guidelines for the Management of Women With Cytologic Abnormalities have been extremely successful—they are now utilized by most clinicians and managed care organizations nationwide. In the last 5 years alone, more than 500,000 copies of the management algorithms have been downloaded from the ASCCP’s Web site (http://www.asccp.org), and many more have been downloaded from the Journal of the American Medical Association and the national guideline clearinghouse.

In large part, this success derived from the fact that most professional societies and federal agencies that deal with cervical cancer screening partnered in their development. Although the ASCCP organized the effort, 29 professional organizations participated. This meant that when groups such as ACOG subsequently developed guidelines for their members, they closely mirrored the 2001 Consensus Guidelines.

The 2006 Consensus Conference included approximately 100 delegates, 28 national and international professional societies, and federal agencies, but the meeting itself was only the final step in a long process. For 18 months, 6 different working groups reviewed the literature and determined where changes were needed.

NEW GUIDELINES ARE EVIDENCE-BASED

“The working groups evaluated hundreds of manuscripts and studies to make certain that the new guidelines remain evidence-based”

Kathy Poole, ASCCP Executive Director

The working groups posted their findings on Internet-based bulletin boards that allowed anyone in the national or international screening community to have input.

NEW GUIDELINES ARE SIMPLER

“One of the key goals of the 2006 Guidelines is simplification”

Dr. Mark Spitzer, ASCCP President and Chairman, Department of Obstetrics and Gynecology, Brookdale University Hospital and Medical Center, Brooklyn

“Many clinicians who manage women with cytologic abnormalities are not obstetricians and gynecologists. Nurse practitioners and family practice clinicians who don’t spend their entire lives dealing with abnormal Pap smears are responsible for much of the cervical cancer screening that takes place nationally,” said Dr. Spitzer. “The 2001 Consensus Guidelines have sometimes been characterized as complex and difficult to follow by such clinicians.”

Atypical squamous cells

HPV DNA-positive ASC-US vs LSIL

No major changes were recommended for the general population with ASC-US. However, since the ALTS trial clearly demonstrated that women with ASC-US who are high-risk HPV DNA-positive are essentially identical to women with LSIL, an effort was made to ensure that recommendations for these 2 groups are identical.

IDENTICAL MANAGEMENT

“Current data clearly indicate that women with ASC-US who are HPV DNA-positive and women with LSIL have the same risk of having high-grade disease and should therefore be managed identically” Dr. Spitzer

Although new data resulted in a number of minor changes to ASC-US recommendations, there are more significant changes in management of ASC-US with “special circumstances.” The 2001 Guidelines identified postmenopausal women and immuno-suppressed women with ASC-US as “special circumstances” to be managed differently than the general population. New guidelines eliminate this distinction.

Limited colposcopy in adolescents

Previously there was no provision for managing adolescents (up to 20 years of age) with ASC-US differently than the general population. New guidelines add adolescents as a “special population,” with different management. This change is based on considerable data demonstrating that the risk of cervical cancer is extremely low in adolescents, and that more than two thirds of adolescents with ASC-US are referred to colposcopy if “reflex” HPV DNA testing or repeat cervical cytology is utilized. Based on the newer data, a more conservative approach, which greatly limits use of colposcopy, will be introduced.

ASC-H

A number of studies have confirmed a high prevalence of CIN 2,3 as well as a high prevalence of high-risk HPV DNA positivity in women with ASC-H compared with women with ASC-US. Therefore, no substantive changes were made in the management recommendations for ASC-H. However, the need for a complete review of cytology, colposcopy, and histology results is downplayed for ASC-H without high-grade CIN.

 

LSIL and CIN 1

Basic management did not change for the general population, but did change for adolescents and postmenopausal women:

Previously, management of CIN 1 depended on whether colposcopy was satisfactory. Either treatment or follow-up was acceptable for women with CIN 1 and satisfactory colposcopy, but a diagnostic excisional procedure was advised for unsatisfactory colposcopy.

This has changed. The importance of a satisfactory colposcopic examination is deemphasized, and conservative follow-up of CIN 1 (which really represents histological manifestations of a productive HPV infection rather than a cancer precursor) is now stressed. Treatment for CIN 1 is particularly discouraged among adolescents.

HSIL and CIN 2,3

Immediate “screen and treat” as a management strategy for HSIL in the general population is emphasized more. As with ASC-H, the need for a complete review of the cytology, colposcopy, and histology results for women with HSIL in whom CIN 2,3 is not identified is deemphasized.

New guidelines no longer require that women with HSIL who do not have biopsy-confirmed CIN 2,3 undergo a diagnostic excisional procedure.

Basic management of CIN 2,3 is modified in only minor ways; however, options for conservative management of adolescents with CIN 2,3 are expanded (as for other clinical scenarios such as ASC-US, LSIL, and HSIL in adolescents).

Atypical glandular cells

HPV DNA STATUS MATTERS

“Based on data obtained since the 2001 Consensus Conference, it now appears reasonable to incorporate knowledge of a woman’s HPV status in management of atypical glandular cell (AGC) cytological abnormalities”

Dr. Charles Dunton, Chair, AGC Working Group, and Director, Division of Gynecological Oncology, Albert Einstein Medical Center, Wynnewood, Pa

Although the 2001 recommendation that almost all women with AGC undergo colposcopy remains, recommended follow-up will be modified to take into account HPV DNA status. Women who are high-risk HPV DNA-negative can be followed less aggressively than those who are high-risk HPV DNA-positive.

Other new guidelines

These include specific guidelines for managing benign endometrial cells identified during routine cytology (in both postmenopausal and cycling women) and benign-appearing glandular cells identified on routine cytology in women who have had a hysterectomy, as well as comprehensive management recommendations for women with biopsy-confirmed cervical adenocarcinoma in situ.

HPV DNA testing

“The 2001 guidelines did not address HPV DNA testing as an adjunct to cervical cytology in women aged 30 and older because HPV DNA testing was not yet FDA approved for this use,” says Dr. Edward J. Wilkinson, Chair, HPV DNA Working Group, and Professor and Vice Chairman, Department of Pathology, University of Florida College of Medicine, Gainesville. Therefore, the Interim Guidance introduced by the ASCCP/NCI/ACS in 2004 was the basis for new recommendations. For the most part, the 2006 Consensus Conference formally adopted the Interim Guidance published in 2004.

Quite a bit of consideration was given to how management will change once the FDA approves genotyping assays that identify HPV 16 and 18 for clinical use. Once such assays become available, the new guidelines indicate that there is sufficient data to support the triage of women who are cytology-negative/HPV DNA-positive, using HPV genotyping assays that identify HPV 16 and 18.

A Vaginal estrogen administration led to greater improvement of both dyspareunia and vaginal dryness in postmenopausal hysterectomized women—despite higher serum estradiol levels with the oral route. Vaginal estrogen had no effect on libido, whereas oral estrogen may lower libido because of related increases in sex hormone binding globulin (SHBG), which decreases free testosterone levels.

Expert Commentary

METHODS Investigators randomized 57 postmenopausal, hysterectomized women to receive oral (0.625 mg of conjugated equine estrogen [CEE]; n=27) or vaginal (0.625 mg of CEE per 1 g of vaginal cream; n=30) estrogen once daily.

Vaginal vascularization and sexual function were assessed through a variety of measures, including serum estradiol, introital color Doppler ultrasound, and personal interviews.

RESULTS After 3 months of treatment, both groups of women had significant increases in the number of vaginal vessels, and “marked” decreases in the pulsatility index.

Unopposed estrogen has its own benefits, risks

In hysterectomized postmenopausal women, unopposed estrogen has been shown to relieve menopausal symptoms and protect against bone loss and osteoporosis-related fractures without increasing the risk of breast cancer or cardiovascular disease.

Don’t be fooled by serum levels

Measurements of serum estradiol levels in women who are taking CEE either orally or vaginally do not truly reflect the total estrogenic load of these patients, because the bulk of estrogen in CEE is estrone sulfate with several equine estrogenic compounds that have activity not reflected by serum estradiol. Consequently, the estrogenicity of the women in this study was not accurately evaluated through the serum estradiol measurements.

Vaginal estrogen is not “topical”

Moreover, the authors refer to the vaginal group as receiving “topical” estrogen—another misconception. Systemic absorption of vaginal estrogen is probably greater and more rapid than with the oral route. It is no surprise that vaginal administration was associated with greater improvement of both dyspareunia and vaginal dryness, because the vagina is exposed to a greater concentration of estrogen when it is administered vaginally than when it is given orally. With oral administration, a significant amount of estrogen is metabolized by the liver, and a much lower dose of estrogen reaches the vaginal epithelium.

Oral estrogen can reduce libido

The lack of improved libido with the oral preparation is not surprising. In fact, some women may experience a decrease in libido with orally administered estrogen because of the associated increases in SHBG. With vaginal administration, SHBG levels are not increased, and sexual desire may improve, especially when vaginal lubrication is improved.

Does either form affect sexual function? Unfortunately, this study was not long enough or sufficiently powered to adequately assess sexual function.

Systemic absorption is high even with vaginal route

The same dose of CEE yields slightly greater benefits to vaginal health and function when it is administered vaginally. When estrogen is given vaginally, systemic absorption is significant—and may be greater than with the oral route.

Indications and contraindications of oral estrogen, consequently, also apply to vaginal administration.

A Vaginal estrogen administration led to greater improvement of both dyspareunia and vaginal dryness in postmenopausal hysterectomized women—despite higher serum estradiol levels with the oral route. Vaginal estrogen had no effect on libido, whereas oral estrogen may lower libido because of related increases in sex hormone binding globulin (SHBG), which decreases free testosterone levels.

Expert Commentary

METHODS Investigators randomized 57 postmenopausal, hysterectomized women to receive oral (0.625 mg of conjugated equine estrogen [CEE]; n=27) or vaginal (0.625 mg of CEE per 1 g of vaginal cream; n=30) estrogen once daily.

Vaginal vascularization and sexual function were assessed through a variety of measures, including serum estradiol, introital color Doppler ultrasound, and personal interviews.

RESULTS After 3 months of treatment, both groups of women had significant increases in the number of vaginal vessels, and “marked” decreases in the pulsatility index.

Unopposed estrogen has its own benefits, risks

In hysterectomized postmenopausal women, unopposed estrogen has been shown to relieve menopausal symptoms and protect against bone loss and osteoporosis-related fractures without increasing the risk of breast cancer or cardiovascular disease.

Don’t be fooled by serum levels

Measurements of serum estradiol levels in women who are taking CEE either orally or vaginally do not truly reflect the total estrogenic load of these patients, because the bulk of estrogen in CEE is estrone sulfate with several equine estrogenic compounds that have activity not reflected by serum estradiol. Consequently, the estrogenicity of the women in this study was not accurately evaluated through the serum estradiol measurements.

Vaginal estrogen is not “topical”

Moreover, the authors refer to the vaginal group as receiving “topical” estrogen—another misconception. Systemic absorption of vaginal estrogen is probably greater and more rapid than with the oral route. It is no surprise that vaginal administration was associated with greater improvement of both dyspareunia and vaginal dryness, because the vagina is exposed to a greater concentration of estrogen when it is administered vaginally than when it is given orally. With oral administration, a significant amount of estrogen is metabolized by the liver, and a much lower dose of estrogen reaches the vaginal epithelium.

Oral estrogen can reduce libido

The lack of improved libido with the oral preparation is not surprising. In fact, some women may experience a decrease in libido with orally administered estrogen because of the associated increases in SHBG. With vaginal administration, SHBG levels are not increased, and sexual desire may improve, especially when vaginal lubrication is improved.

Does either form affect sexual function? Unfortunately, this study was not long enough or sufficiently powered to adequately assess sexual function.

Systemic absorption is high even with vaginal route

The same dose of CEE yields slightly greater benefits to vaginal health and function when it is administered vaginally. When estrogen is given vaginally, systemic absorption is significant—and may be greater than with the oral route.

Indications and contraindications of oral estrogen, consequently, also apply to vaginal administration.

A Vaginal estrogen administration led to greater improvement of both dyspareunia and vaginal dryness in postmenopausal hysterectomized women—despite higher serum estradiol levels with the oral route. Vaginal estrogen had no effect on libido, whereas oral estrogen may lower libido because of related increases in sex hormone binding globulin (SHBG), which decreases free testosterone levels.

Expert Commentary

METHODS Investigators randomized 57 postmenopausal, hysterectomized women to receive oral (0.625 mg of conjugated equine estrogen [CEE]; n=27) or vaginal (0.625 mg of CEE per 1 g of vaginal cream; n=30) estrogen once daily.

Vaginal vascularization and sexual function were assessed through a variety of measures, including serum estradiol, introital color Doppler ultrasound, and personal interviews.

RESULTS After 3 months of treatment, both groups of women had significant increases in the number of vaginal vessels, and “marked” decreases in the pulsatility index.

Unopposed estrogen has its own benefits, risks

In hysterectomized postmenopausal women, unopposed estrogen has been shown to relieve menopausal symptoms and protect against bone loss and osteoporosis-related fractures without increasing the risk of breast cancer or cardiovascular disease.

Don’t be fooled by serum levels

Measurements of serum estradiol levels in women who are taking CEE either orally or vaginally do not truly reflect the total estrogenic load of these patients, because the bulk of estrogen in CEE is estrone sulfate with several equine estrogenic compounds that have activity not reflected by serum estradiol. Consequently, the estrogenicity of the women in this study was not accurately evaluated through the serum estradiol measurements.

Vaginal estrogen is not “topical”

Moreover, the authors refer to the vaginal group as receiving “topical” estrogen—another misconception. Systemic absorption of vaginal estrogen is probably greater and more rapid than with the oral route. It is no surprise that vaginal administration was associated with greater improvement of both dyspareunia and vaginal dryness, because the vagina is exposed to a greater concentration of estrogen when it is administered vaginally than when it is given orally. With oral administration, a significant amount of estrogen is metabolized by the liver, and a much lower dose of estrogen reaches the vaginal epithelium.

Oral estrogen can reduce libido

The lack of improved libido with the oral preparation is not surprising. In fact, some women may experience a decrease in libido with orally administered estrogen because of the associated increases in SHBG. With vaginal administration, SHBG levels are not increased, and sexual desire may improve, especially when vaginal lubrication is improved.

Does either form affect sexual function? Unfortunately, this study was not long enough or sufficiently powered to adequately assess sexual function.

Systemic absorption is high even with vaginal route

The same dose of CEE yields slightly greater benefits to vaginal health and function when it is administered vaginally. When estrogen is given vaginally, systemic absorption is significant—and may be greater than with the oral route.

Indications and contraindications of oral estrogen, consequently, also apply to vaginal administration.

A Yes and no. For stress urinary incontinence, there was substantial reliability and interobserver consistency in interpretations of urodynamic tests.

However, reliability was only moderate for diagnoses of detrusor overactivity, and interobserver consistency was only fair. Thus, urodynamic testing may not be as informative for this diagnosis.

Expert Commentary

Urodynamic testing has traditionally been used to evaluate and distinguish between different types of urinary incontinence. Weidner and colleagues¹ demonstrated that subjective symptoms may not always predict the ultimate diagnosis and recommended urodynamic evaluation prior to initiation of therapy or surgical intervention.

Urodynamic testing is not without limitations:

Interobserver agreement was moderate

METHODS Six physicians reviewed the records (ie, blinded study packets that retained key portions of the patient’s history and urodynamic findings) of 100 women who presented to a urogynecology or female urology practice and were referred for urodynamic testing. The 6 physician reviewers assigned both clinical and International Continence Society diagnoses to each record and reviewed the packets again at least 4 months later.

RESULTS Reviewers were consistent in their own evaluations of urodynamic tracings and diagnoses. Nor was there much intra-observer difference between female urologists and urogynecologists.

However, interobserver agreement varied with the diagnosis, and also was lower when a particular sign or symptom was present, suggesting that the absence of symptoms and signs was used to rule out diagnoses, as opposed to ruling them in.

Detrusor overactivity a more elusive diagnosis?

These results are consistent with earlier studies that showed stress incontinence to be more reliably diagnosed on both simple cystometry and multichannel cystometry, and which showed that symptoms alone are not a sufficient basis for surgical management.

However, the interpretation of detrusor overactivity appears to be less reliable and less consistent. The demonstration of urge incontinence with office cystometry has been shown to predict detrusor overactivity, but its absence does not preclude this diagnosis.⁴

Urodynamic testing is most useful for diagnosing stress incontinence

This study occurred at a single institution without standardized guidelines for interpretation of urodynamic test results. A multicenter study by Zimmern et al⁵ for the Urinary Incontinence and Treatment Network demonstrated excellent inter-rater reliability for urodynamics between both central and local-site reviewers—after establishing uniform certification standards.

Thus, it seems clear that standardized guidelines and modules would assist in the interpretation of urodynamic tests. Until then, urodynamic testing should entail a concerted effort to standardize the interpretation of urodynamic diagnoses.

A Yes and no. For stress urinary incontinence, there was substantial reliability and interobserver consistency in interpretations of urodynamic tests.

However, reliability was only moderate for diagnoses of detrusor overactivity, and interobserver consistency was only fair. Thus, urodynamic testing may not be as informative for this diagnosis.

Expert Commentary

Urodynamic testing has traditionally been used to evaluate and distinguish between different types of urinary incontinence. Weidner and colleagues¹ demonstrated that subjective symptoms may not always predict the ultimate diagnosis and recommended urodynamic evaluation prior to initiation of therapy or surgical intervention.

Urodynamic testing is not without limitations:

Interobserver agreement was moderate

METHODS Six physicians reviewed the records (ie, blinded study packets that retained key portions of the patient’s history and urodynamic findings) of 100 women who presented to a urogynecology or female urology practice and were referred for urodynamic testing. The 6 physician reviewers assigned both clinical and International Continence Society diagnoses to each record and reviewed the packets again at least 4 months later.

RESULTS Reviewers were consistent in their own evaluations of urodynamic tracings and diagnoses. Nor was there much intra-observer difference between female urologists and urogynecologists.

However, interobserver agreement varied with the diagnosis, and also was lower when a particular sign or symptom was present, suggesting that the absence of symptoms and signs was used to rule out diagnoses, as opposed to ruling them in.

Detrusor overactivity a more elusive diagnosis?

These results are consistent with earlier studies that showed stress incontinence to be more reliably diagnosed on both simple cystometry and multichannel cystometry, and which showed that symptoms alone are not a sufficient basis for surgical management.

However, the interpretation of detrusor overactivity appears to be less reliable and less consistent. The demonstration of urge incontinence with office cystometry has been shown to predict detrusor overactivity, but its absence does not preclude this diagnosis.⁴

Urodynamic testing is most useful for diagnosing stress incontinence

This study occurred at a single institution without standardized guidelines for interpretation of urodynamic test results. A multicenter study by Zimmern et al⁵ for the Urinary Incontinence and Treatment Network demonstrated excellent inter-rater reliability for urodynamics between both central and local-site reviewers—after establishing uniform certification standards.

Thus, it seems clear that standardized guidelines and modules would assist in the interpretation of urodynamic tests. Until then, urodynamic testing should entail a concerted effort to standardize the interpretation of urodynamic diagnoses.

A Yes and no. For stress urinary incontinence, there was substantial reliability and interobserver consistency in interpretations of urodynamic tests.

However, reliability was only moderate for diagnoses of detrusor overactivity, and interobserver consistency was only fair. Thus, urodynamic testing may not be as informative for this diagnosis.

Expert Commentary

Urodynamic testing has traditionally been used to evaluate and distinguish between different types of urinary incontinence. Weidner and colleagues¹ demonstrated that subjective symptoms may not always predict the ultimate diagnosis and recommended urodynamic evaluation prior to initiation of therapy or surgical intervention.

Urodynamic testing is not without limitations:

Interobserver agreement was moderate

METHODS Six physicians reviewed the records (ie, blinded study packets that retained key portions of the patient’s history and urodynamic findings) of 100 women who presented to a urogynecology or female urology practice and were referred for urodynamic testing. The 6 physician reviewers assigned both clinical and International Continence Society diagnoses to each record and reviewed the packets again at least 4 months later.

RESULTS Reviewers were consistent in their own evaluations of urodynamic tracings and diagnoses. Nor was there much intra-observer difference between female urologists and urogynecologists.

However, interobserver agreement varied with the diagnosis, and also was lower when a particular sign or symptom was present, suggesting that the absence of symptoms and signs was used to rule out diagnoses, as opposed to ruling them in.

Detrusor overactivity a more elusive diagnosis?

These results are consistent with earlier studies that showed stress incontinence to be more reliably diagnosed on both simple cystometry and multichannel cystometry, and which showed that symptoms alone are not a sufficient basis for surgical management.

However, the interpretation of detrusor overactivity appears to be less reliable and less consistent. The demonstration of urge incontinence with office cystometry has been shown to predict detrusor overactivity, but its absence does not preclude this diagnosis.⁴

Urodynamic testing is most useful for diagnosing stress incontinence

This study occurred at a single institution without standardized guidelines for interpretation of urodynamic test results. A multicenter study by Zimmern et al⁵ for the Urinary Incontinence and Treatment Network demonstrated excellent inter-rater reliability for urodynamics between both central and local-site reviewers—after establishing uniform certification standards.

Thus, it seems clear that standardized guidelines and modules would assist in the interpretation of urodynamic tests. Until then, urodynamic testing should entail a concerted effort to standardize the interpretation of urodynamic diagnoses.

A In this Markov model, surgical options—bilateral salpingo-oophorectomy alone or with bilateral mastectomy—were more cost-effective than chemoprevention (tamoxifen for breast cancer or oral contraceptives for ovarian cancer) or surveillance. For BRCA mutation carriers 35 years of age, the 2 surgeries combined had an incremental cost-effectiveness ratio over oophorectomy alone of $2,352 per life-year for BRCA1 and $100 per life-year for BRCA2. After adjustment for quality of life, oophorectomy was the most cost-effective strategy for women with BRCA1 mutations, and had an incremental cost-effectiveness ratio of $2,281 per life-year for women with BRCA2 mutations.

Expert Commentary

The significance of hereditary predisposition to cancer is now widely understood. Although this predisposition is responsible for only 5% to 10% of the breast and ovarian cancers that occur each year, it offers the potential for prevention and early diagnosis. This study further validates the utility of risk-reducing surgery—not just from an individual patient’s point of view, but also from a public health and healthcare financing perspective.

Newer data shed light on age-specific incidence

This study benefited from fairly recent data on the age-specific incidence of breast and ovarian cancer in women with germline mutations.¹ Thus, the 2 surgical options and chemoprevention could be more accurately compared with surveillance to determine the most economical and effective approach. Surveillance consisted of annual mammography; breast ultrasonography if necessary; clinical breast examination; and semiannual gynecologic examinations that included pelvic examination, ultrasonography, and CA-125 studies.

Strengths and weaknesses of the study

Anderson and colleagues are to be commended for a well-planned and well-executed study. All modeling studies are limited by their assumptions, as the authors observed, and it appears they went to great lengths to optimize their parameters.

I would take issue with only 2 points. First, the authors stated that “BRCA-positive women who develop cancer would have the same conditional probability of death as women with cancer in the general population.” Several groups have reported better survival among women with BRCA mutations who develop advanced ovarian cancer than among matched controls whose disease occurred on a sporadic basis.^2,3

The authors also assumed that women at age 35 who were given estrogen therapy until age 50 after prophylactic oophorectomy had no heightened risk for breast cancer, other than the risk already conferred by BRCA1 or BRCA2 mutations. However, in a report cited by the authors, Rebbeck et al⁴ described a decrease in the risk of breast cancer among these women—a decrease that hormone therapy did not alter.

Younger women benefited most

Not surprisingly, cost-effectiveness varied with age, with younger women benefiting the most from the preventive strategies.

A dislike of prophylactic mastectomy

Because women are reluctant to undergo prophylactic mastectomy, even when a BRCA1 or BRCA2 mutation is present, the findings were adjusted for quality of life, which negated the greater cost-effectiveness of surgical strategies that included mastectomy.

Choice of preventive option should involve both patient and physician

Ultimately, a risk-reducing surgical strategy should be chosen by the patient after a thorough review with her physician of the options and their risks and benefits. However, as this report concludes, “Any primary prevention strategy would be cost-effective or cost-saving compared with surveillance.”

A In this Markov model, surgical options—bilateral salpingo-oophorectomy alone or with bilateral mastectomy—were more cost-effective than chemoprevention (tamoxifen for breast cancer or oral contraceptives for ovarian cancer) or surveillance. For BRCA mutation carriers 35 years of age, the 2 surgeries combined had an incremental cost-effectiveness ratio over oophorectomy alone of $2,352 per life-year for BRCA1 and $100 per life-year for BRCA2. After adjustment for quality of life, oophorectomy was the most cost-effective strategy for women with BRCA1 mutations, and had an incremental cost-effectiveness ratio of $2,281 per life-year for women with BRCA2 mutations.

Expert Commentary

The significance of hereditary predisposition to cancer is now widely understood. Although this predisposition is responsible for only 5% to 10% of the breast and ovarian cancers that occur each year, it offers the potential for prevention and early diagnosis. This study further validates the utility of risk-reducing surgery—not just from an individual patient’s point of view, but also from a public health and healthcare financing perspective.

Newer data shed light on age-specific incidence

This study benefited from fairly recent data on the age-specific incidence of breast and ovarian cancer in women with germline mutations.¹ Thus, the 2 surgical options and chemoprevention could be more accurately compared with surveillance to determine the most economical and effective approach. Surveillance consisted of annual mammography; breast ultrasonography if necessary; clinical breast examination; and semiannual gynecologic examinations that included pelvic examination, ultrasonography, and CA-125 studies.

Strengths and weaknesses of the study

Anderson and colleagues are to be commended for a well-planned and well-executed study. All modeling studies are limited by their assumptions, as the authors observed, and it appears they went to great lengths to optimize their parameters.

I would take issue with only 2 points. First, the authors stated that “BRCA-positive women who develop cancer would have the same conditional probability of death as women with cancer in the general population.” Several groups have reported better survival among women with BRCA mutations who develop advanced ovarian cancer than among matched controls whose disease occurred on a sporadic basis.^2,3

The authors also assumed that women at age 35 who were given estrogen therapy until age 50 after prophylactic oophorectomy had no heightened risk for breast cancer, other than the risk already conferred by BRCA1 or BRCA2 mutations. However, in a report cited by the authors, Rebbeck et al⁴ described a decrease in the risk of breast cancer among these women—a decrease that hormone therapy did not alter.

Younger women benefited most

Not surprisingly, cost-effectiveness varied with age, with younger women benefiting the most from the preventive strategies.

A dislike of prophylactic mastectomy

Because women are reluctant to undergo prophylactic mastectomy, even when a BRCA1 or BRCA2 mutation is present, the findings were adjusted for quality of life, which negated the greater cost-effectiveness of surgical strategies that included mastectomy.

Choice of preventive option should involve both patient and physician

Ultimately, a risk-reducing surgical strategy should be chosen by the patient after a thorough review with her physician of the options and their risks and benefits. However, as this report concludes, “Any primary prevention strategy would be cost-effective or cost-saving compared with surveillance.”

A In this Markov model, surgical options—bilateral salpingo-oophorectomy alone or with bilateral mastectomy—were more cost-effective than chemoprevention (tamoxifen for breast cancer or oral contraceptives for ovarian cancer) or surveillance. For BRCA mutation carriers 35 years of age, the 2 surgeries combined had an incremental cost-effectiveness ratio over oophorectomy alone of $2,352 per life-year for BRCA1 and $100 per life-year for BRCA2. After adjustment for quality of life, oophorectomy was the most cost-effective strategy for women with BRCA1 mutations, and had an incremental cost-effectiveness ratio of $2,281 per life-year for women with BRCA2 mutations.

Expert Commentary

The significance of hereditary predisposition to cancer is now widely understood. Although this predisposition is responsible for only 5% to 10% of the breast and ovarian cancers that occur each year, it offers the potential for prevention and early diagnosis. This study further validates the utility of risk-reducing surgery—not just from an individual patient’s point of view, but also from a public health and healthcare financing perspective.

Newer data shed light on age-specific incidence

This study benefited from fairly recent data on the age-specific incidence of breast and ovarian cancer in women with germline mutations.¹ Thus, the 2 surgical options and chemoprevention could be more accurately compared with surveillance to determine the most economical and effective approach. Surveillance consisted of annual mammography; breast ultrasonography if necessary; clinical breast examination; and semiannual gynecologic examinations that included pelvic examination, ultrasonography, and CA-125 studies.

Strengths and weaknesses of the study

Anderson and colleagues are to be commended for a well-planned and well-executed study. All modeling studies are limited by their assumptions, as the authors observed, and it appears they went to great lengths to optimize their parameters.

I would take issue with only 2 points. First, the authors stated that “BRCA-positive women who develop cancer would have the same conditional probability of death as women with cancer in the general population.” Several groups have reported better survival among women with BRCA mutations who develop advanced ovarian cancer than among matched controls whose disease occurred on a sporadic basis.^2,3

The authors also assumed that women at age 35 who were given estrogen therapy until age 50 after prophylactic oophorectomy had no heightened risk for breast cancer, other than the risk already conferred by BRCA1 or BRCA2 mutations. However, in a report cited by the authors, Rebbeck et al⁴ described a decrease in the risk of breast cancer among these women—a decrease that hormone therapy did not alter.

Younger women benefited most

Not surprisingly, cost-effectiveness varied with age, with younger women benefiting the most from the preventive strategies.

A dislike of prophylactic mastectomy

Because women are reluctant to undergo prophylactic mastectomy, even when a BRCA1 or BRCA2 mutation is present, the findings were adjusted for quality of life, which negated the greater cost-effectiveness of surgical strategies that included mastectomy.

Choice of preventive option should involve both patient and physician

Ultimately, a risk-reducing surgical strategy should be chosen by the patient after a thorough review with her physician of the options and their risks and benefits. However, as this report concludes, “Any primary prevention strategy would be cost-effective or cost-saving compared with surveillance.”

A Not at this time, although more women 35 to 60 years of age with cervical intraepithelial neoplasia 2 or higher (CIN2+) harbor DNA evidence of the human papillomavirus (HPV) than manifest cytologic changes of neoplastic transformation. That is, HPV-positive results are more common than abnormal cytology in screening. Thus, the authors present an alternative strategy of beginning screening with hybrid capture 2 (HC2) testing for HPV in women aged 35 and above, with cytologic analysis of HC2-positive cases second and colposcopy for those who test positive (atypical squamous cell changes or higher-grade abnormalities) in both. They fall short of recommending this tactic for clinical practice.

Strengths of the study include large population

In this massive multicenter trial involving more than 33,000 women, participants were randomly assigned to screening with conventional cytology or to the experimental arm. This was a high-risk population 35 to 60 years of age, of which just slightly over 50% had undergone cervical screening within 4 years. In the first phase of the trial, which is the focus of this study, women in the experimental arm underwent screening with liquid-based cytology and HPV testing, and in the second phase, women were screened using HPV testing alone. The key endpoint for comparison: histology-confirmed CIN2+ after an abnormal screening test. Abnormal screening was defined as cytologic results of atypical squamous cells of undetermined significance or higher (ASCUS+) in the conventional cytology group, and ASCUS+ or a positive HC2 test in the experimental arm.

Because of the large sample size, it was deemed impossible to perform the “gold standard” diagnostic test (colposcopy and biopsy) in women with negative screening, so true sensitivity, specificity, and negative predictive value of the testing strategies could not be determined (TABLE). Because of this, the authors labeled and compared detection rates of CIN2+ in the 2 screening groups as “relative sensitivity.”

TABLE

How to “screen” a screening test

SCREENING TEST RESULTS	HISTOLOGIC FINDINGS
	DISEASE PRESENT	DISEASE ABSENT
The ideal screening test focuses on disease that is prevalent. To determine the value of the test, all patients undergo definitive evaluation—in the case of cervical cancer screening, this would entail colposcopy and biopsy—to determine the actual disease rate and the “disease-free” rate.
Positive	a (true positive)	b (false positive)
Negative	c (false negative)	d (true negative)
A test’s sensitivity is defined as a/a+c, specificity as d/b+d, positive predictive value as a/a+b, and negative predictive value as d/c+d.
If the entire screening population is not screened with the “gold-standard” reference test, the values of “c” and “d” cannot be determined. In the study by Ronco and colleagues, the only true rate that can be calculated is positive predictive value.

Expert Commentary

This study leads to several key conclusions:

Practice recommendations

A Not at this time, although more women 35 to 60 years of age with cervical intraepithelial neoplasia 2 or higher (CIN2+) harbor DNA evidence of the human papillomavirus (HPV) than manifest cytologic changes of neoplastic transformation. That is, HPV-positive results are more common than abnormal cytology in screening. Thus, the authors present an alternative strategy of beginning screening with hybrid capture 2 (HC2) testing for HPV in women aged 35 and above, with cytologic analysis of HC2-positive cases second and colposcopy for those who test positive (atypical squamous cell changes or higher-grade abnormalities) in both. They fall short of recommending this tactic for clinical practice.

Strengths of the study include large population

In this massive multicenter trial involving more than 33,000 women, participants were randomly assigned to screening with conventional cytology or to the experimental arm. This was a high-risk population 35 to 60 years of age, of which just slightly over 50% had undergone cervical screening within 4 years. In the first phase of the trial, which is the focus of this study, women in the experimental arm underwent screening with liquid-based cytology and HPV testing, and in the second phase, women were screened using HPV testing alone. The key endpoint for comparison: histology-confirmed CIN2+ after an abnormal screening test. Abnormal screening was defined as cytologic results of atypical squamous cells of undetermined significance or higher (ASCUS+) in the conventional cytology group, and ASCUS+ or a positive HC2 test in the experimental arm.

Because of the large sample size, it was deemed impossible to perform the “gold standard” diagnostic test (colposcopy and biopsy) in women with negative screening, so true sensitivity, specificity, and negative predictive value of the testing strategies could not be determined (TABLE). Because of this, the authors labeled and compared detection rates of CIN2+ in the 2 screening groups as “relative sensitivity.”

TABLE

How to “screen” a screening test

SCREENING TEST RESULTS	HISTOLOGIC FINDINGS
	DISEASE PRESENT	DISEASE ABSENT
The ideal screening test focuses on disease that is prevalent. To determine the value of the test, all patients undergo definitive evaluation—in the case of cervical cancer screening, this would entail colposcopy and biopsy—to determine the actual disease rate and the “disease-free” rate.
Positive	a (true positive)	b (false positive)
Negative	c (false negative)	d (true negative)
A test’s sensitivity is defined as a/a+c, specificity as d/b+d, positive predictive value as a/a+b, and negative predictive value as d/c+d.
If the entire screening population is not screened with the “gold-standard” reference test, the values of “c” and “d” cannot be determined. In the study by Ronco and colleagues, the only true rate that can be calculated is positive predictive value.

Expert Commentary

This study leads to several key conclusions:

Practice recommendations

A Not at this time, although more women 35 to 60 years of age with cervical intraepithelial neoplasia 2 or higher (CIN2+) harbor DNA evidence of the human papillomavirus (HPV) than manifest cytologic changes of neoplastic transformation. That is, HPV-positive results are more common than abnormal cytology in screening. Thus, the authors present an alternative strategy of beginning screening with hybrid capture 2 (HC2) testing for HPV in women aged 35 and above, with cytologic analysis of HC2-positive cases second and colposcopy for those who test positive (atypical squamous cell changes or higher-grade abnormalities) in both. They fall short of recommending this tactic for clinical practice.

Strengths of the study include large population

In this massive multicenter trial involving more than 33,000 women, participants were randomly assigned to screening with conventional cytology or to the experimental arm. This was a high-risk population 35 to 60 years of age, of which just slightly over 50% had undergone cervical screening within 4 years. In the first phase of the trial, which is the focus of this study, women in the experimental arm underwent screening with liquid-based cytology and HPV testing, and in the second phase, women were screened using HPV testing alone. The key endpoint for comparison: histology-confirmed CIN2+ after an abnormal screening test. Abnormal screening was defined as cytologic results of atypical squamous cells of undetermined significance or higher (ASCUS+) in the conventional cytology group, and ASCUS+ or a positive HC2 test in the experimental arm.

Because of the large sample size, it was deemed impossible to perform the “gold standard” diagnostic test (colposcopy and biopsy) in women with negative screening, so true sensitivity, specificity, and negative predictive value of the testing strategies could not be determined (TABLE). Because of this, the authors labeled and compared detection rates of CIN2+ in the 2 screening groups as “relative sensitivity.”

TABLE

How to “screen” a screening test

SCREENING TEST RESULTS	HISTOLOGIC FINDINGS
	DISEASE PRESENT	DISEASE ABSENT
The ideal screening test focuses on disease that is prevalent. To determine the value of the test, all patients undergo definitive evaluation—in the case of cervical cancer screening, this would entail colposcopy and biopsy—to determine the actual disease rate and the “disease-free” rate.
Positive	a (true positive)	b (false positive)
Negative	c (false negative)	d (true negative)
A test’s sensitivity is defined as a/a+c, specificity as d/b+d, positive predictive value as a/a+b, and negative predictive value as d/c+d.
If the entire screening population is not screened with the “gold-standard” reference test, the values of “c” and “d” cannot be determined. In the study by Ronco and colleagues, the only true rate that can be calculated is positive predictive value.

Expert Commentary

This study leads to several key conclusions:

Practice recommendations