Robert L. Barbieri, MD

Case: Patient seeks clarification and next steps on her breast density classification
Your patient, a 51-year-old postmenopausal woman (G0P0) in good health, had an annual screening mammogram that showed no evidence of malignancy. She is white and has a mother with a history of breast cancer. She has never had a breast biopsy. Following the mammogram, she received a letter from the imaging center, stating:

She calls your office and asks, “What should I do next?”

Breasts are composed of fibrous, glandular, and adipose tissue. If the breasts contain a lot of fibrous and glandular tissue, and little adipose tissue, they are considered to be “dense.” Using mammography, the current standard is to report the density of breast tissue using 4 categories:

Dense breast tissue is defined to include the 2 categories heterogeneously dense and extremely dense.

Observational studies have reported that dense breast tissue is associated with an increased risk of breast cancer, and dense breast tissue makes it more difficult to detect breast cancer on mammography. According to data from the Breast Cancer Surveillance Consortium, among women aged 50 or older, the relative risk of breast cancer stratified by the 4 categories of breast density is 0.59, 1.00, 1.46, and 1.77, for almost entirely fatty, scattered fibroglandular densities, heterogeneously dense, and extremely dense, respectively.¹ In one study, the sensitivity of mammography to detect breast cancer was 82% to 88% for women with nondense breasts and 62% to 69% in women with dense breasts.² These data have catalyzed investigators to explore the use of supplemental imaging to enhance cancer detection in women with dense breasts.

The link between breast density and breast cancer risk and reduced sensitivity of mammography also has catalyzed activists and legislators to champion breast density notification laws, which have passed in more than 20 states. These laws require facilities that perform mammography to notify women with dense breasts that this finding is associated with an increased risk of breast cancer and that dense breasts reduce the ability of mammography to detect cancer. In some states, the law mandates that women with dense breasts be offered supplemental ultrasound imaging and that insurers must cover the cost of the ultrasound studies. Many of the laws recommend that the patient discuss the situation with the clinician who ordered the mammogram.

When I first saw the recommendation for patients to contact me about how to manage dense breasts, my initial response was, “Who? Me?” I felt ill equipped to provide any useful advice and suspected that many of my patients knew more than I about this issue.

Based on a review of the evidence, my current clinical recommendation is outlined in the 2 options below, including a low-resource utilization option and a high-resource utilization option. For patients, physicians, and health systems that are concerned that excessive breast cancer screening tests might cause more harm than benefit, the identification of dense breasts on mammogram is unlikely to be a trigger to perform any additional testing. In this situation, the pragmatic low-resource option is most relevant.

Alternatively, for patients and physicians who strongly believe in the value of screening mammography (see “Utilize tomosynthesis digital mammography technology for your patients” below), a reasonable strategy is to recommend that women with dense breasts and an increased risk for breast cancer be offered supplemental imaging.

In this editorial I elaborate these 2 approaches to breast cancer screening in women with dense breasts.
 

A pragmatic, low-resource utilization screening approach for women with dense breasts
There are no published randomized clinical trials that provide high-quality evidence on what to do if dense breasts are identified on mammography.³ Authors of observational studies have evaluated the potential role of supplemental imaging, including ultrasound and magnetic resonance imaging (MRI), in the management of dense breast tissue (see “Supplemental breast cancer screening modalities” below). Supplemental imaging involves complex trade-offs, balancing the potential benefit of identifying occult early breast cancer lesions not identified by mammography with the risk of subjecting many women without cancer to additional testing and unnecessary biopsies.

A pragmatic, low-resource utilization plan for women with dense breasts involves emphasizing that mammography is the best available screening tool and that annual or biennial mammography is the foundation of all current approaches to breast cancer screening. Supplemental imaging is unnecessary with this approach because there is no evidence that it reduces breast cancer mortality. There is, however, substantial evidence that using supplemental imaging for all women with dense breasts will result in little benefit and great costs, including many unnecessary biopsies.^1,4 Women with dense breasts also could consider annual clinical breast examination.

 

A high-resource utilization screening approach
There are no randomized trials to help guide recommendations about how to respond to a finding of dense breasts on mammography. In addition to breast density, many factors influence breast cancer risk, including a patient’s:

Women with both dense breasts and an increased risk of breast cancer may reap the greatest benefit from supplemental imaging, such as ultrasonography. Therefore, a two-step approach can help.

Step 1: Assess breast cancer risk. This can be accomplished using one of many calculators. Three that are commonly used are the:

The BCSC calculator uses age, race/ethnicity, first-degree relatives with breast cancer, a history of a breast biopsy, and breast density to calculate a 5-year risk of developing breast cancer.

The BCRAT tool uses current age, race/ethnicity, age at menarche, age at first live-birth of a child, number of first-degree relatives with breast cancer, a history of breast biopsies, and the identification of atypical hyperplasia to calculate a 5-year risk of breast cancer.

The IBIS model uses many more variables, including a detailed family history to calculate a 10-year and lifetime risk of breast cancer. If a patient has ductal carcinoma in situ, lobular carcinoma in situ, chest irradiation before age 30 years, or known BRCA1 or BRCA2 mutations, she is instructed not to use the risk calculators because they are at very high risk for breast cancer, and they need an individualized intensive plan for monitoring and prevention (see MRI section in “Supplemental breast cancer screening modalities” above).

Step 2: Use breast density and breast cancer risk to develop a screening plan. The NIH Breast Cancer Surveillance Consortium has published data estimating the risk that a woman with a mammogram negative for cancer will develop breast cancer within the next 12 months (based on her age, breast density, and breast cancer risk—calculated with the BCSC tool).⁸

It reported an increased risk of breast cancer diagnosed within 12 months following a mammogram that was negative for cancer in women with extremely dense breasts and a BCSC 5-year risk of breast cancer of 1.67% or greater and in women with heterogeneously dense breasts and a BCSC 5-year risk of breast cancer of 2.5% or greater.⁸

Using these cutoffs it is estimated that 24% of all women with heterogeneously or extremely dense breasts would be offered supplemental screening with a modality such as ultrasound, and 76% would be guided not to have supplemental screening because their risk of developing breast cancer in the 12 months following their negative mammogram is low.

If this guidance is followed, it would require 694 supplemental ultrasound studies and many biopsies to detect 1 additional breast cancer, significantly increasing overall health care costs.⁸ In many states insurers do not cover supplemental ultrasound imaging of the breasts. In most states insurers require preauthorization for supplemental MRI of the breasts. You need to know the insurance practices in the state to help guide decision making about supplemental imaging. The approach described above is consistent with the American College of Obstetricians and Gynecologists recommendation that women with dense breasts, who are asymptomaticand have no additional risk factors for breast cancer, do not need to be offered supplemental imaging.⁹

Case: Next steps
The BCSC calculator reveals that the 51-year-old woman with a family history of breast cancer and a mammogram showing extremely dense breasts has a 5-year risk of breast cancer of 2.68%. Given that this risk is elevated, this patient could be offered supplemental ultrasound screening and annual breast clinical examination. In addition, she could be further counseled about breast cancer chemoprevention options.¹⁰

Women with a strong family history of breast and/or ovarian cancer also could be referred for genetic counseling and BRCA testing.¹¹ The risk of having a BRCA mutation can be calculated using the BRCAPRO tool.¹²

Most women with dense breast tissue on mammography will never develop breast cancer. Yet the presence of dense breast tissue both increases the risk of breast cancer and decreases the sensitivity of mammography to detect cancer. There are no high-quality data from randomized trials to help guide our recommendations concerning the management of dense breasts identified on mammography. Yet many states have laws that suggest patients ask you to provide advice about breast density.

Patients, clinicians, and health systems vary in their confidence in the clinical value of breast cancer screening programs. Consequently, there is no “right answer” to this vexing problem. The standard of care is to support a range of options tailored to the specific clinical characteristics and needs of each patient. 
 

Case: Patient seeks clarification and next steps on her breast density classification
Your patient, a 51-year-old postmenopausal woman (G0P0) in good health, had an annual screening mammogram that showed no evidence of malignancy. She is white and has a mother with a history of breast cancer. She has never had a breast biopsy. Following the mammogram, she received a letter from the imaging center, stating:

She calls your office and asks, “What should I do next?”

Breasts are composed of fibrous, glandular, and adipose tissue. If the breasts contain a lot of fibrous and glandular tissue, and little adipose tissue, they are considered to be “dense.” Using mammography, the current standard is to report the density of breast tissue using 4 categories:

Dense breast tissue is defined to include the 2 categories heterogeneously dense and extremely dense.

Observational studies have reported that dense breast tissue is associated with an increased risk of breast cancer, and dense breast tissue makes it more difficult to detect breast cancer on mammography. According to data from the Breast Cancer Surveillance Consortium, among women aged 50 or older, the relative risk of breast cancer stratified by the 4 categories of breast density is 0.59, 1.00, 1.46, and 1.77, for almost entirely fatty, scattered fibroglandular densities, heterogeneously dense, and extremely dense, respectively.¹ In one study, the sensitivity of mammography to detect breast cancer was 82% to 88% for women with nondense breasts and 62% to 69% in women with dense breasts.² These data have catalyzed investigators to explore the use of supplemental imaging to enhance cancer detection in women with dense breasts.

The link between breast density and breast cancer risk and reduced sensitivity of mammography also has catalyzed activists and legislators to champion breast density notification laws, which have passed in more than 20 states. These laws require facilities that perform mammography to notify women with dense breasts that this finding is associated with an increased risk of breast cancer and that dense breasts reduce the ability of mammography to detect cancer. In some states, the law mandates that women with dense breasts be offered supplemental ultrasound imaging and that insurers must cover the cost of the ultrasound studies. Many of the laws recommend that the patient discuss the situation with the clinician who ordered the mammogram.

When I first saw the recommendation for patients to contact me about how to manage dense breasts, my initial response was, “Who? Me?” I felt ill equipped to provide any useful advice and suspected that many of my patients knew more than I about this issue.

Based on a review of the evidence, my current clinical recommendation is outlined in the 2 options below, including a low-resource utilization option and a high-resource utilization option. For patients, physicians, and health systems that are concerned that excessive breast cancer screening tests might cause more harm than benefit, the identification of dense breasts on mammogram is unlikely to be a trigger to perform any additional testing. In this situation, the pragmatic low-resource option is most relevant.

Alternatively, for patients and physicians who strongly believe in the value of screening mammography (see “Utilize tomosynthesis digital mammography technology for your patients” below), a reasonable strategy is to recommend that women with dense breasts and an increased risk for breast cancer be offered supplemental imaging.

In this editorial I elaborate these 2 approaches to breast cancer screening in women with dense breasts.
 

A pragmatic, low-resource utilization screening approach for women with dense breasts
There are no published randomized clinical trials that provide high-quality evidence on what to do if dense breasts are identified on mammography.³ Authors of observational studies have evaluated the potential role of supplemental imaging, including ultrasound and magnetic resonance imaging (MRI), in the management of dense breast tissue (see “Supplemental breast cancer screening modalities” below). Supplemental imaging involves complex trade-offs, balancing the potential benefit of identifying occult early breast cancer lesions not identified by mammography with the risk of subjecting many women without cancer to additional testing and unnecessary biopsies.

A pragmatic, low-resource utilization plan for women with dense breasts involves emphasizing that mammography is the best available screening tool and that annual or biennial mammography is the foundation of all current approaches to breast cancer screening. Supplemental imaging is unnecessary with this approach because there is no evidence that it reduces breast cancer mortality. There is, however, substantial evidence that using supplemental imaging for all women with dense breasts will result in little benefit and great costs, including many unnecessary biopsies.^1,4 Women with dense breasts also could consider annual clinical breast examination.

 

A high-resource utilization screening approach
There are no randomized trials to help guide recommendations about how to respond to a finding of dense breasts on mammography. In addition to breast density, many factors influence breast cancer risk, including a patient’s:

Women with both dense breasts and an increased risk of breast cancer may reap the greatest benefit from supplemental imaging, such as ultrasonography. Therefore, a two-step approach can help.

Step 1: Assess breast cancer risk. This can be accomplished using one of many calculators. Three that are commonly used are the:

The BCSC calculator uses age, race/ethnicity, first-degree relatives with breast cancer, a history of a breast biopsy, and breast density to calculate a 5-year risk of developing breast cancer.

The BCRAT tool uses current age, race/ethnicity, age at menarche, age at first live-birth of a child, number of first-degree relatives with breast cancer, a history of breast biopsies, and the identification of atypical hyperplasia to calculate a 5-year risk of breast cancer.

The IBIS model uses many more variables, including a detailed family history to calculate a 10-year and lifetime risk of breast cancer. If a patient has ductal carcinoma in situ, lobular carcinoma in situ, chest irradiation before age 30 years, or known BRCA1 or BRCA2 mutations, she is instructed not to use the risk calculators because they are at very high risk for breast cancer, and they need an individualized intensive plan for monitoring and prevention (see MRI section in “Supplemental breast cancer screening modalities” above).

Step 2: Use breast density and breast cancer risk to develop a screening plan. The NIH Breast Cancer Surveillance Consortium has published data estimating the risk that a woman with a mammogram negative for cancer will develop breast cancer within the next 12 months (based on her age, breast density, and breast cancer risk—calculated with the BCSC tool).⁸

It reported an increased risk of breast cancer diagnosed within 12 months following a mammogram that was negative for cancer in women with extremely dense breasts and a BCSC 5-year risk of breast cancer of 1.67% or greater and in women with heterogeneously dense breasts and a BCSC 5-year risk of breast cancer of 2.5% or greater.⁸

Using these cutoffs it is estimated that 24% of all women with heterogeneously or extremely dense breasts would be offered supplemental screening with a modality such as ultrasound, and 76% would be guided not to have supplemental screening because their risk of developing breast cancer in the 12 months following their negative mammogram is low.

If this guidance is followed, it would require 694 supplemental ultrasound studies and many biopsies to detect 1 additional breast cancer, significantly increasing overall health care costs.⁸ In many states insurers do not cover supplemental ultrasound imaging of the breasts. In most states insurers require preauthorization for supplemental MRI of the breasts. You need to know the insurance practices in the state to help guide decision making about supplemental imaging. The approach described above is consistent with the American College of Obstetricians and Gynecologists recommendation that women with dense breasts, who are asymptomaticand have no additional risk factors for breast cancer, do not need to be offered supplemental imaging.⁹

Case: Next steps
The BCSC calculator reveals that the 51-year-old woman with a family history of breast cancer and a mammogram showing extremely dense breasts has a 5-year risk of breast cancer of 2.68%. Given that this risk is elevated, this patient could be offered supplemental ultrasound screening and annual breast clinical examination. In addition, she could be further counseled about breast cancer chemoprevention options.¹⁰

Women with a strong family history of breast and/or ovarian cancer also could be referred for genetic counseling and BRCA testing.¹¹ The risk of having a BRCA mutation can be calculated using the BRCAPRO tool.¹²

Most women with dense breast tissue on mammography will never develop breast cancer. Yet the presence of dense breast tissue both increases the risk of breast cancer and decreases the sensitivity of mammography to detect cancer. There are no high-quality data from randomized trials to help guide our recommendations concerning the management of dense breasts identified on mammography. Yet many states have laws that suggest patients ask you to provide advice about breast density.

Patients, clinicians, and health systems vary in their confidence in the clinical value of breast cancer screening programs. Consequently, there is no “right answer” to this vexing problem. The standard of care is to support a range of options tailored to the specific clinical characteristics and needs of each patient. 
 

Case: Patient seeks clarification and next steps on her breast density classification
Your patient, a 51-year-old postmenopausal woman (G0P0) in good health, had an annual screening mammogram that showed no evidence of malignancy. She is white and has a mother with a history of breast cancer. She has never had a breast biopsy. Following the mammogram, she received a letter from the imaging center, stating:

She calls your office and asks, “What should I do next?”

Breasts are composed of fibrous, glandular, and adipose tissue. If the breasts contain a lot of fibrous and glandular tissue, and little adipose tissue, they are considered to be “dense.” Using mammography, the current standard is to report the density of breast tissue using 4 categories:

Dense breast tissue is defined to include the 2 categories heterogeneously dense and extremely dense.

Observational studies have reported that dense breast tissue is associated with an increased risk of breast cancer, and dense breast tissue makes it more difficult to detect breast cancer on mammography. According to data from the Breast Cancer Surveillance Consortium, among women aged 50 or older, the relative risk of breast cancer stratified by the 4 categories of breast density is 0.59, 1.00, 1.46, and 1.77, for almost entirely fatty, scattered fibroglandular densities, heterogeneously dense, and extremely dense, respectively.¹ In one study, the sensitivity of mammography to detect breast cancer was 82% to 88% for women with nondense breasts and 62% to 69% in women with dense breasts.² These data have catalyzed investigators to explore the use of supplemental imaging to enhance cancer detection in women with dense breasts.

The link between breast density and breast cancer risk and reduced sensitivity of mammography also has catalyzed activists and legislators to champion breast density notification laws, which have passed in more than 20 states. These laws require facilities that perform mammography to notify women with dense breasts that this finding is associated with an increased risk of breast cancer and that dense breasts reduce the ability of mammography to detect cancer. In some states, the law mandates that women with dense breasts be offered supplemental ultrasound imaging and that insurers must cover the cost of the ultrasound studies. Many of the laws recommend that the patient discuss the situation with the clinician who ordered the mammogram.

When I first saw the recommendation for patients to contact me about how to manage dense breasts, my initial response was, “Who? Me?” I felt ill equipped to provide any useful advice and suspected that many of my patients knew more than I about this issue.

Based on a review of the evidence, my current clinical recommendation is outlined in the 2 options below, including a low-resource utilization option and a high-resource utilization option. For patients, physicians, and health systems that are concerned that excessive breast cancer screening tests might cause more harm than benefit, the identification of dense breasts on mammogram is unlikely to be a trigger to perform any additional testing. In this situation, the pragmatic low-resource option is most relevant.

Alternatively, for patients and physicians who strongly believe in the value of screening mammography (see “Utilize tomosynthesis digital mammography technology for your patients” below), a reasonable strategy is to recommend that women with dense breasts and an increased risk for breast cancer be offered supplemental imaging.

In this editorial I elaborate these 2 approaches to breast cancer screening in women with dense breasts.
 

A pragmatic, low-resource utilization screening approach for women with dense breasts
There are no published randomized clinical trials that provide high-quality evidence on what to do if dense breasts are identified on mammography.³ Authors of observational studies have evaluated the potential role of supplemental imaging, including ultrasound and magnetic resonance imaging (MRI), in the management of dense breast tissue (see “Supplemental breast cancer screening modalities” below). Supplemental imaging involves complex trade-offs, balancing the potential benefit of identifying occult early breast cancer lesions not identified by mammography with the risk of subjecting many women without cancer to additional testing and unnecessary biopsies.

A pragmatic, low-resource utilization plan for women with dense breasts involves emphasizing that mammography is the best available screening tool and that annual or biennial mammography is the foundation of all current approaches to breast cancer screening. Supplemental imaging is unnecessary with this approach because there is no evidence that it reduces breast cancer mortality. There is, however, substantial evidence that using supplemental imaging for all women with dense breasts will result in little benefit and great costs, including many unnecessary biopsies.^1,4 Women with dense breasts also could consider annual clinical breast examination.

 

A high-resource utilization screening approach
There are no randomized trials to help guide recommendations about how to respond to a finding of dense breasts on mammography. In addition to breast density, many factors influence breast cancer risk, including a patient’s:

Women with both dense breasts and an increased risk of breast cancer may reap the greatest benefit from supplemental imaging, such as ultrasonography. Therefore, a two-step approach can help.

Step 1: Assess breast cancer risk. This can be accomplished using one of many calculators. Three that are commonly used are the:

The BCSC calculator uses age, race/ethnicity, first-degree relatives with breast cancer, a history of a breast biopsy, and breast density to calculate a 5-year risk of developing breast cancer.

The BCRAT tool uses current age, race/ethnicity, age at menarche, age at first live-birth of a child, number of first-degree relatives with breast cancer, a history of breast biopsies, and the identification of atypical hyperplasia to calculate a 5-year risk of breast cancer.

The IBIS model uses many more variables, including a detailed family history to calculate a 10-year and lifetime risk of breast cancer. If a patient has ductal carcinoma in situ, lobular carcinoma in situ, chest irradiation before age 30 years, or known BRCA1 or BRCA2 mutations, she is instructed not to use the risk calculators because they are at very high risk for breast cancer, and they need an individualized intensive plan for monitoring and prevention (see MRI section in “Supplemental breast cancer screening modalities” above).

Step 2: Use breast density and breast cancer risk to develop a screening plan. The NIH Breast Cancer Surveillance Consortium has published data estimating the risk that a woman with a mammogram negative for cancer will develop breast cancer within the next 12 months (based on her age, breast density, and breast cancer risk—calculated with the BCSC tool).⁸

It reported an increased risk of breast cancer diagnosed within 12 months following a mammogram that was negative for cancer in women with extremely dense breasts and a BCSC 5-year risk of breast cancer of 1.67% or greater and in women with heterogeneously dense breasts and a BCSC 5-year risk of breast cancer of 2.5% or greater.⁸

Using these cutoffs it is estimated that 24% of all women with heterogeneously or extremely dense breasts would be offered supplemental screening with a modality such as ultrasound, and 76% would be guided not to have supplemental screening because their risk of developing breast cancer in the 12 months following their negative mammogram is low.

If this guidance is followed, it would require 694 supplemental ultrasound studies and many biopsies to detect 1 additional breast cancer, significantly increasing overall health care costs.⁸ In many states insurers do not cover supplemental ultrasound imaging of the breasts. In most states insurers require preauthorization for supplemental MRI of the breasts. You need to know the insurance practices in the state to help guide decision making about supplemental imaging. The approach described above is consistent with the American College of Obstetricians and Gynecologists recommendation that women with dense breasts, who are asymptomaticand have no additional risk factors for breast cancer, do not need to be offered supplemental imaging.⁹

Case: Next steps
The BCSC calculator reveals that the 51-year-old woman with a family history of breast cancer and a mammogram showing extremely dense breasts has a 5-year risk of breast cancer of 2.68%. Given that this risk is elevated, this patient could be offered supplemental ultrasound screening and annual breast clinical examination. In addition, she could be further counseled about breast cancer chemoprevention options.¹⁰

Women with a strong family history of breast and/or ovarian cancer also could be referred for genetic counseling and BRCA testing.¹¹ The risk of having a BRCA mutation can be calculated using the BRCAPRO tool.¹²

Most women with dense breast tissue on mammography will never develop breast cancer. Yet the presence of dense breast tissue both increases the risk of breast cancer and decreases the sensitivity of mammography to detect cancer. There are no high-quality data from randomized trials to help guide our recommendations concerning the management of dense breasts identified on mammography. Yet many states have laws that suggest patients ask you to provide advice about breast density.

Patients, clinicians, and health systems vary in their confidence in the clinical value of breast cancer screening programs. Consequently, there is no “right answer” to this vexing problem. The standard of care is to support a range of options tailored to the specific clinical characteristics and needs of each patient. 
 

When Dr. Harald zur Hausen received the 2008 Nobel Prize in Physiology or Medicine for his discovery of the link between human papillomavirus (HPV) infections and genital cancers, he completed a 40-year odyssey to prove that viruses caused human cancer. Initially, zur Hausen, working in the University of Pennsylvania laboratory of the noted virologists Drs. Werner and Gertrude Henle, discovered that the Epstein-Barr virus was involved in the development of Burkitt lymphoma.¹ On return to his native Germany, he sought a link between HPV and genital tumors.²

First he isolated HPV 6 and HPV 11 directly from genital warts.³ Then zur Hausen utilized the nucleic acid sequences from HPV6 and the technique of low stringency hybridization to discover HPV 16 and HPV 18 in cervical cancer specimens.^4,5 Oncogenic HPV DNA contains 2 genes that produce the oncoproteins E6 and E7. E6 increases the degradation of p53 and E7 inactivates the retino-blastoma protein.⁶ The double-hit inactivation of 2 tumor suppressor genes, p53 and retinoblastoma protein, increases the mitotic activity of the infected cells, eventually leading to cancer.

zur Hausen tried to persuade companies to develop anti-HPV vaccines but was rebuffed for years. Today, building on his research, we have HPV vaccines that are 2-valent (against HPV types 16 and 18), 4-valent (against HPV types 6, 11, 16, and 18), and 9-valent (against HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58). zur Hausen richly deserved the Nobel Prize for his life-saving discoveries.

Cervical, vulvar, and vaginal cancers
HPV types 16 and 18 cause about 70% of cervical cancers. HPV types 31, 33, 45, 52, and 58 cause about 20% of cervical cancers.⁷ The 2-, 4-, and 9-valent HPV vaccines have been demonstrated to prevent premalignant cervical disease, including cervical intraepithelial neoplasia (CIN) 2 and CIN 3 and adenocarcinoma in situ.^8–11 The development of a 9-valent HPV vaccine is an important advance because it provides more complete immunization against cancer causing viruses.

Approximately 70% of vaginal cancers are caused by HPV infections.¹² Among squamous cell vulvar cancers, HPV is detected in approximately 70% of cancers with warty or basaloid histology and 12% of cancers with keratinizing histology.¹³ In vulvar cancer, HPV 16, 33, and 18 are the most common types detected, representing 73%, 7%, and 5% of cases, respectively. The HPV 4- and 9-valent vaccines have been reported to reduce precancerous lesions of the vagina and vulva.^9,11 In most trials, vaccinations that occur before exposure to HPV through sexual encounters appear to provide greater protection than vaccinations that occur after HPV infection.

Anal cancer
Approximately 90% of anal cancers are caused by HPV infection, and HPV types 16 and 18 are detected in 81% and 4% of anal cancers, respectively.¹⁴ Among men who have sex with men, the HPV 4-valent vaccine reduced the rate of anal intraepithelial neoplasia, a precursor to anal cancer, by 50%.¹⁵ Women receiving the HPV 2-valent vaccine had an 84% reduction in the detection of anal cancer involving HPV types 16 and 18.¹⁶

Penile cancer
Approximately 48% of penile cancers harbor oncogenic HPV types.17 Among penile cancers the prevalence of HPV varies from 22% in verrucous cancer to 66% in basaloid and warty cancer. The most prevalent HPV types were 16, 6, and 18, which were observed in 31%, 7%, and 7% of the cancers, respectively.17 Penile cancer is not common and there are no studies directly demonstrating that HPV vaccination prevents penile cancer.

Oropharyngeal cancer
The rate of oropharyngeal cancer caused by HPV is rising rapidly and increasing more rapidly among men than among women.¹⁸ Remarkably, HPV-induced oropharyngeal cancer is projected to become more common than cervical cancer in 2020.¹⁸

In one report, 72% of oropharyngeal cancers harbored HPV 16, and antibodies against the HPV 16 oncoproteins E6 and E7 were detected in the blood of 64% of the cancer cases.¹⁹ In a case control study, having 6 or more lifetime oral-sex partners was associated with a 3.4-fold (95% confidence interval, 1.5 to 6.5) increased risk of developing oropharyngeal cancer.¹⁹

According to a population survey, 10% of men and 3.6% of women harbor HPV viruses in their oropharynx.²⁰ In this study approximately 50% of the HPV viruses detected were high-risk types, with the following rank-order prevalence from highest to lowest: 16, 66, 51, 39, 56, 52, 59, 18, 53, 45, 35, 33, and 31.²⁰ Theoretically, the 9-valent vaccine, with protection against HPV types 16, 18, 31, 33, 45, and 52, may be an optimal choice to prevent HPV-induced oropharyngeal cancer because of its broad coverage.

No study has yet proven that HPV vaccination reduces the risk of developing oropharyngeal cancer, but one study demonstrated that vaccination of girls against HPV types 16 and 18 reduced oral carriage of HPV 16 and HPV 18 by 93%.²¹ Vaccinating boys against HPV has been reported to be cost effective because it could reduce the high health care expenditures associated with treating oropharyngeal cancer.²²

Will you be an immunization champion?
Although HPV vaccination reduces the disease burden of cervical, vulvar, vaginal, and anal neoplasia, the CDC reported that, as of 2013, only 38% of girls and 14% of boys in the United States had received 3 doses of HPV vaccine.²³ The realization that oropharyngeal cancer caused by HPV is rapidly increasing may provide another catalyst to redouble our efforts to increase the vaccination rates for both boys and girls.

zur Hausen and many other experts have passionately advocated for vaccinating all boys and girls in order to maximize the beneficial effects of HPV vaccination.24 Every clinician can become an immunization champion by advocating that all boys and girls be vaccinated against HPV.

Share your thoughts on this article! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

When Dr. Harald zur Hausen received the 2008 Nobel Prize in Physiology or Medicine for his discovery of the link between human papillomavirus (HPV) infections and genital cancers, he completed a 40-year odyssey to prove that viruses caused human cancer. Initially, zur Hausen, working in the University of Pennsylvania laboratory of the noted virologists Drs. Werner and Gertrude Henle, discovered that the Epstein-Barr virus was involved in the development of Burkitt lymphoma.¹ On return to his native Germany, he sought a link between HPV and genital tumors.²

First he isolated HPV 6 and HPV 11 directly from genital warts.³ Then zur Hausen utilized the nucleic acid sequences from HPV6 and the technique of low stringency hybridization to discover HPV 16 and HPV 18 in cervical cancer specimens.^4,5 Oncogenic HPV DNA contains 2 genes that produce the oncoproteins E6 and E7. E6 increases the degradation of p53 and E7 inactivates the retino-blastoma protein.⁶ The double-hit inactivation of 2 tumor suppressor genes, p53 and retinoblastoma protein, increases the mitotic activity of the infected cells, eventually leading to cancer.

zur Hausen tried to persuade companies to develop anti-HPV vaccines but was rebuffed for years. Today, building on his research, we have HPV vaccines that are 2-valent (against HPV types 16 and 18), 4-valent (against HPV types 6, 11, 16, and 18), and 9-valent (against HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58). zur Hausen richly deserved the Nobel Prize for his life-saving discoveries.

Cervical, vulvar, and vaginal cancers
HPV types 16 and 18 cause about 70% of cervical cancers. HPV types 31, 33, 45, 52, and 58 cause about 20% of cervical cancers.⁷ The 2-, 4-, and 9-valent HPV vaccines have been demonstrated to prevent premalignant cervical disease, including cervical intraepithelial neoplasia (CIN) 2 and CIN 3 and adenocarcinoma in situ.^8–11 The development of a 9-valent HPV vaccine is an important advance because it provides more complete immunization against cancer causing viruses.

Approximately 70% of vaginal cancers are caused by HPV infections.¹² Among squamous cell vulvar cancers, HPV is detected in approximately 70% of cancers with warty or basaloid histology and 12% of cancers with keratinizing histology.¹³ In vulvar cancer, HPV 16, 33, and 18 are the most common types detected, representing 73%, 7%, and 5% of cases, respectively. The HPV 4- and 9-valent vaccines have been reported to reduce precancerous lesions of the vagina and vulva.^9,11 In most trials, vaccinations that occur before exposure to HPV through sexual encounters appear to provide greater protection than vaccinations that occur after HPV infection.

Anal cancer
Approximately 90% of anal cancers are caused by HPV infection, and HPV types 16 and 18 are detected in 81% and 4% of anal cancers, respectively.¹⁴ Among men who have sex with men, the HPV 4-valent vaccine reduced the rate of anal intraepithelial neoplasia, a precursor to anal cancer, by 50%.¹⁵ Women receiving the HPV 2-valent vaccine had an 84% reduction in the detection of anal cancer involving HPV types 16 and 18.¹⁶

Penile cancer
Approximately 48% of penile cancers harbor oncogenic HPV types.17 Among penile cancers the prevalence of HPV varies from 22% in verrucous cancer to 66% in basaloid and warty cancer. The most prevalent HPV types were 16, 6, and 18, which were observed in 31%, 7%, and 7% of the cancers, respectively.17 Penile cancer is not common and there are no studies directly demonstrating that HPV vaccination prevents penile cancer.

Oropharyngeal cancer
The rate of oropharyngeal cancer caused by HPV is rising rapidly and increasing more rapidly among men than among women.¹⁸ Remarkably, HPV-induced oropharyngeal cancer is projected to become more common than cervical cancer in 2020.¹⁸

In one report, 72% of oropharyngeal cancers harbored HPV 16, and antibodies against the HPV 16 oncoproteins E6 and E7 were detected in the blood of 64% of the cancer cases.¹⁹ In a case control study, having 6 or more lifetime oral-sex partners was associated with a 3.4-fold (95% confidence interval, 1.5 to 6.5) increased risk of developing oropharyngeal cancer.¹⁹

According to a population survey, 10% of men and 3.6% of women harbor HPV viruses in their oropharynx.²⁰ In this study approximately 50% of the HPV viruses detected were high-risk types, with the following rank-order prevalence from highest to lowest: 16, 66, 51, 39, 56, 52, 59, 18, 53, 45, 35, 33, and 31.²⁰ Theoretically, the 9-valent vaccine, with protection against HPV types 16, 18, 31, 33, 45, and 52, may be an optimal choice to prevent HPV-induced oropharyngeal cancer because of its broad coverage.

No study has yet proven that HPV vaccination reduces the risk of developing oropharyngeal cancer, but one study demonstrated that vaccination of girls against HPV types 16 and 18 reduced oral carriage of HPV 16 and HPV 18 by 93%.²¹ Vaccinating boys against HPV has been reported to be cost effective because it could reduce the high health care expenditures associated with treating oropharyngeal cancer.²²

Will you be an immunization champion?
Although HPV vaccination reduces the disease burden of cervical, vulvar, vaginal, and anal neoplasia, the CDC reported that, as of 2013, only 38% of girls and 14% of boys in the United States had received 3 doses of HPV vaccine.²³ The realization that oropharyngeal cancer caused by HPV is rapidly increasing may provide another catalyst to redouble our efforts to increase the vaccination rates for both boys and girls.

zur Hausen and many other experts have passionately advocated for vaccinating all boys and girls in order to maximize the beneficial effects of HPV vaccination.24 Every clinician can become an immunization champion by advocating that all boys and girls be vaccinated against HPV.

Share your thoughts on this article! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

When Dr. Harald zur Hausen received the 2008 Nobel Prize in Physiology or Medicine for his discovery of the link between human papillomavirus (HPV) infections and genital cancers, he completed a 40-year odyssey to prove that viruses caused human cancer. Initially, zur Hausen, working in the University of Pennsylvania laboratory of the noted virologists Drs. Werner and Gertrude Henle, discovered that the Epstein-Barr virus was involved in the development of Burkitt lymphoma.¹ On return to his native Germany, he sought a link between HPV and genital tumors.²

First he isolated HPV 6 and HPV 11 directly from genital warts.³ Then zur Hausen utilized the nucleic acid sequences from HPV6 and the technique of low stringency hybridization to discover HPV 16 and HPV 18 in cervical cancer specimens.^4,5 Oncogenic HPV DNA contains 2 genes that produce the oncoproteins E6 and E7. E6 increases the degradation of p53 and E7 inactivates the retino-blastoma protein.⁶ The double-hit inactivation of 2 tumor suppressor genes, p53 and retinoblastoma protein, increases the mitotic activity of the infected cells, eventually leading to cancer.

zur Hausen tried to persuade companies to develop anti-HPV vaccines but was rebuffed for years. Today, building on his research, we have HPV vaccines that are 2-valent (against HPV types 16 and 18), 4-valent (against HPV types 6, 11, 16, and 18), and 9-valent (against HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58). zur Hausen richly deserved the Nobel Prize for his life-saving discoveries.

Cervical, vulvar, and vaginal cancers
HPV types 16 and 18 cause about 70% of cervical cancers. HPV types 31, 33, 45, 52, and 58 cause about 20% of cervical cancers.⁷ The 2-, 4-, and 9-valent HPV vaccines have been demonstrated to prevent premalignant cervical disease, including cervical intraepithelial neoplasia (CIN) 2 and CIN 3 and adenocarcinoma in situ.^8–11 The development of a 9-valent HPV vaccine is an important advance because it provides more complete immunization against cancer causing viruses.

Approximately 70% of vaginal cancers are caused by HPV infections.¹² Among squamous cell vulvar cancers, HPV is detected in approximately 70% of cancers with warty or basaloid histology and 12% of cancers with keratinizing histology.¹³ In vulvar cancer, HPV 16, 33, and 18 are the most common types detected, representing 73%, 7%, and 5% of cases, respectively. The HPV 4- and 9-valent vaccines have been reported to reduce precancerous lesions of the vagina and vulva.^9,11 In most trials, vaccinations that occur before exposure to HPV through sexual encounters appear to provide greater protection than vaccinations that occur after HPV infection.

Anal cancer
Approximately 90% of anal cancers are caused by HPV infection, and HPV types 16 and 18 are detected in 81% and 4% of anal cancers, respectively.¹⁴ Among men who have sex with men, the HPV 4-valent vaccine reduced the rate of anal intraepithelial neoplasia, a precursor to anal cancer, by 50%.¹⁵ Women receiving the HPV 2-valent vaccine had an 84% reduction in the detection of anal cancer involving HPV types 16 and 18.¹⁶

Penile cancer
Approximately 48% of penile cancers harbor oncogenic HPV types.17 Among penile cancers the prevalence of HPV varies from 22% in verrucous cancer to 66% in basaloid and warty cancer. The most prevalent HPV types were 16, 6, and 18, which were observed in 31%, 7%, and 7% of the cancers, respectively.17 Penile cancer is not common and there are no studies directly demonstrating that HPV vaccination prevents penile cancer.

Oropharyngeal cancer
The rate of oropharyngeal cancer caused by HPV is rising rapidly and increasing more rapidly among men than among women.¹⁸ Remarkably, HPV-induced oropharyngeal cancer is projected to become more common than cervical cancer in 2020.¹⁸

In one report, 72% of oropharyngeal cancers harbored HPV 16, and antibodies against the HPV 16 oncoproteins E6 and E7 were detected in the blood of 64% of the cancer cases.¹⁹ In a case control study, having 6 or more lifetime oral-sex partners was associated with a 3.4-fold (95% confidence interval, 1.5 to 6.5) increased risk of developing oropharyngeal cancer.¹⁹

According to a population survey, 10% of men and 3.6% of women harbor HPV viruses in their oropharynx.²⁰ In this study approximately 50% of the HPV viruses detected were high-risk types, with the following rank-order prevalence from highest to lowest: 16, 66, 51, 39, 56, 52, 59, 18, 53, 45, 35, 33, and 31.²⁰ Theoretically, the 9-valent vaccine, with protection against HPV types 16, 18, 31, 33, 45, and 52, may be an optimal choice to prevent HPV-induced oropharyngeal cancer because of its broad coverage.

No study has yet proven that HPV vaccination reduces the risk of developing oropharyngeal cancer, but one study demonstrated that vaccination of girls against HPV types 16 and 18 reduced oral carriage of HPV 16 and HPV 18 by 93%.²¹ Vaccinating boys against HPV has been reported to be cost effective because it could reduce the high health care expenditures associated with treating oropharyngeal cancer.²²

Will you be an immunization champion?
Although HPV vaccination reduces the disease burden of cervical, vulvar, vaginal, and anal neoplasia, the CDC reported that, as of 2013, only 38% of girls and 14% of boys in the United States had received 3 doses of HPV vaccine.²³ The realization that oropharyngeal cancer caused by HPV is rapidly increasing may provide another catalyst to redouble our efforts to increase the vaccination rates for both boys and girls.

zur Hausen and many other experts have passionately advocated for vaccinating all boys and girls in order to maximize the beneficial effects of HPV vaccination.24 Every clinician can become an immunization champion by advocating that all boys and girls be vaccinated against HPV.

Share your thoughts on this article! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Every year graduating medical students participate in the exciting, challenging, and anxiety-provoking process of applying to residency programs. After thousands of miles of travel, dozens of hotel overnight stays, and many interviews, the students are matched to their residency training site and begin specialty training. The first residency “Match” (conducted by the National Resident Matching Program) occurred in 1952 with 6,000 applicants and 10,400 available PGY-1 positions. In the 2014 Match, 34,270 applicants vied for 26,678 PGY-1 positions.¹

Of great interest to medical students and educators are the relative balance of applicants and residency positions in each specialty, and the magnitude of risk that a US medical student will not match to his or her chosen specialty. For students who have devoted years preparing for residency training in a chosen specialty the day they learn that they have not matched is heartbreaking, painful, and a test of their resilience. The Match does sponsor a supplemental offer and acceptance program that helps unmatched applicants to identify unfilled positions. This process helps unmatched applicants to continue their professional development without a delay.

When researching for this editorial, I consulted the National Resident Matching Program’s Results and Data 2014 Main Residency Match.¹ The TABLE shows the percentage of US medical school seniors who ranked a specialty as their only choice and did not match. The fields of neurosurgery, otolaryngology, plastic surgery, and orthopedic surgery had the greatest number of US medical school seniors (more than 17%) who ranked a specialty as their only choice and did not match in 2014. The fields of physical medicine and rehabilitation, dermatology, general surgery-categorical, obstetrics and gynecology, and radiation oncology had 6% to 11% of US seniors who ranked a specialty as their only choice not match in 2014. By contrast, almost all US applicants successfully matched in the fields of medicine-pediatrics, diagnostic radiology, anesthesiology, pathology, internal medicine-categorical, neurology, pediatrics-categorical, family medicine, emergency medicine, and psychiatry.

Clearly, obstetrics and gynecology is a popular career choice among medical students. Why might that be so?

Deeply meaningful relationships, continuity of care, plus surgical challenges
Students select a career in obstetrics and gynecology for many reasons. During their clinical experience in obstetrics and gynecology students often experience deeply meaningful relationships with patients at poignant life milestones, including conception, birth, and major surgery. In addition, students recognize that the field offers the opportunity to develop continuity relationships with patients and perform surgical procedures. Primary care specialists often develop deeply rewarding relationships with patients and their families that extend over decades, but they do not perform many surgical procedures. Procedure specialists, including general and orthopedic surgeons, perform hundreds of operations each year, but seldom have the opportunity to develop relationships with patients that last decades. Obstetrics and gynecology offers the combination of long-term continuity relationships with patients and training in surgical procedures.

Many other aspects of the field are attractive to students. Students report that their passion for the field was catalyzed by many factors and experiences, including:

Renew your enthusiasm for our field—mentor!
For practicing obstetricians and gynecologists the combined challenges of complex cases with unfortunate clinical outcomes, ever growing administrative burdens, and the difficulty of balancing work and personal-life may cause them to doubt the wisdom of choosing to train in the field. One of the best ways to erase these doubts is to mentor one of the about

1,250 newly minted physicians who will start their training in obstetrics and gynecology in the summer of 2015 or one of the approximately 1,300 US medical students who will apply to enter the field in 2016.

Medical students have a world of opportunity in front of them, with dozens of exciting career options. The fact that so many students select a career in our field is heartening. These students will become excellent obstetrician-gynecologistsand dedicate themselves to advancingthe health of the 150 million women in the United States. 
 

Would you select a career in obstetrics and gynecology again? Answer the Quick Poll on the home page and see how others have voted.

Why did you select a career in obstetrics and gynecology? Tell us at [email protected] Please include your name and city and state.

Every year graduating medical students participate in the exciting, challenging, and anxiety-provoking process of applying to residency programs. After thousands of miles of travel, dozens of hotel overnight stays, and many interviews, the students are matched to their residency training site and begin specialty training. The first residency “Match” (conducted by the National Resident Matching Program) occurred in 1952 with 6,000 applicants and 10,400 available PGY-1 positions. In the 2014 Match, 34,270 applicants vied for 26,678 PGY-1 positions.¹

Of great interest to medical students and educators are the relative balance of applicants and residency positions in each specialty, and the magnitude of risk that a US medical student will not match to his or her chosen specialty. For students who have devoted years preparing for residency training in a chosen specialty the day they learn that they have not matched is heartbreaking, painful, and a test of their resilience. The Match does sponsor a supplemental offer and acceptance program that helps unmatched applicants to identify unfilled positions. This process helps unmatched applicants to continue their professional development without a delay.

When researching for this editorial, I consulted the National Resident Matching Program’s Results and Data 2014 Main Residency Match.¹ The TABLE shows the percentage of US medical school seniors who ranked a specialty as their only choice and did not match. The fields of neurosurgery, otolaryngology, plastic surgery, and orthopedic surgery had the greatest number of US medical school seniors (more than 17%) who ranked a specialty as their only choice and did not match in 2014. The fields of physical medicine and rehabilitation, dermatology, general surgery-categorical, obstetrics and gynecology, and radiation oncology had 6% to 11% of US seniors who ranked a specialty as their only choice not match in 2014. By contrast, almost all US applicants successfully matched in the fields of medicine-pediatrics, diagnostic radiology, anesthesiology, pathology, internal medicine-categorical, neurology, pediatrics-categorical, family medicine, emergency medicine, and psychiatry.

Clearly, obstetrics and gynecology is a popular career choice among medical students. Why might that be so?

Deeply meaningful relationships, continuity of care, plus surgical challenges
Students select a career in obstetrics and gynecology for many reasons. During their clinical experience in obstetrics and gynecology students often experience deeply meaningful relationships with patients at poignant life milestones, including conception, birth, and major surgery. In addition, students recognize that the field offers the opportunity to develop continuity relationships with patients and perform surgical procedures. Primary care specialists often develop deeply rewarding relationships with patients and their families that extend over decades, but they do not perform many surgical procedures. Procedure specialists, including general and orthopedic surgeons, perform hundreds of operations each year, but seldom have the opportunity to develop relationships with patients that last decades. Obstetrics and gynecology offers the combination of long-term continuity relationships with patients and training in surgical procedures.

Many other aspects of the field are attractive to students. Students report that their passion for the field was catalyzed by many factors and experiences, including:

Renew your enthusiasm for our field—mentor!
For practicing obstetricians and gynecologists the combined challenges of complex cases with unfortunate clinical outcomes, ever growing administrative burdens, and the difficulty of balancing work and personal-life may cause them to doubt the wisdom of choosing to train in the field. One of the best ways to erase these doubts is to mentor one of the about

1,250 newly minted physicians who will start their training in obstetrics and gynecology in the summer of 2015 or one of the approximately 1,300 US medical students who will apply to enter the field in 2016.

Medical students have a world of opportunity in front of them, with dozens of exciting career options. The fact that so many students select a career in our field is heartening. These students will become excellent obstetrician-gynecologistsand dedicate themselves to advancingthe health of the 150 million women in the United States. 
 

Would you select a career in obstetrics and gynecology again? Answer the Quick Poll on the home page and see how others have voted.

Why did you select a career in obstetrics and gynecology? Tell us at [email protected] Please include your name and city and state.

Every year graduating medical students participate in the exciting, challenging, and anxiety-provoking process of applying to residency programs. After thousands of miles of travel, dozens of hotel overnight stays, and many interviews, the students are matched to their residency training site and begin specialty training. The first residency “Match” (conducted by the National Resident Matching Program) occurred in 1952 with 6,000 applicants and 10,400 available PGY-1 positions. In the 2014 Match, 34,270 applicants vied for 26,678 PGY-1 positions.¹

Of great interest to medical students and educators are the relative balance of applicants and residency positions in each specialty, and the magnitude of risk that a US medical student will not match to his or her chosen specialty. For students who have devoted years preparing for residency training in a chosen specialty the day they learn that they have not matched is heartbreaking, painful, and a test of their resilience. The Match does sponsor a supplemental offer and acceptance program that helps unmatched applicants to identify unfilled positions. This process helps unmatched applicants to continue their professional development without a delay.

When researching for this editorial, I consulted the National Resident Matching Program’s Results and Data 2014 Main Residency Match.¹ The TABLE shows the percentage of US medical school seniors who ranked a specialty as their only choice and did not match. The fields of neurosurgery, otolaryngology, plastic surgery, and orthopedic surgery had the greatest number of US medical school seniors (more than 17%) who ranked a specialty as their only choice and did not match in 2014. The fields of physical medicine and rehabilitation, dermatology, general surgery-categorical, obstetrics and gynecology, and radiation oncology had 6% to 11% of US seniors who ranked a specialty as their only choice not match in 2014. By contrast, almost all US applicants successfully matched in the fields of medicine-pediatrics, diagnostic radiology, anesthesiology, pathology, internal medicine-categorical, neurology, pediatrics-categorical, family medicine, emergency medicine, and psychiatry.

Clearly, obstetrics and gynecology is a popular career choice among medical students. Why might that be so?

Deeply meaningful relationships, continuity of care, plus surgical challenges
Students select a career in obstetrics and gynecology for many reasons. During their clinical experience in obstetrics and gynecology students often experience deeply meaningful relationships with patients at poignant life milestones, including conception, birth, and major surgery. In addition, students recognize that the field offers the opportunity to develop continuity relationships with patients and perform surgical procedures. Primary care specialists often develop deeply rewarding relationships with patients and their families that extend over decades, but they do not perform many surgical procedures. Procedure specialists, including general and orthopedic surgeons, perform hundreds of operations each year, but seldom have the opportunity to develop relationships with patients that last decades. Obstetrics and gynecology offers the combination of long-term continuity relationships with patients and training in surgical procedures.

Many other aspects of the field are attractive to students. Students report that their passion for the field was catalyzed by many factors and experiences, including:

Renew your enthusiasm for our field—mentor!
For practicing obstetricians and gynecologists the combined challenges of complex cases with unfortunate clinical outcomes, ever growing administrative burdens, and the difficulty of balancing work and personal-life may cause them to doubt the wisdom of choosing to train in the field. One of the best ways to erase these doubts is to mentor one of the about

1,250 newly minted physicians who will start their training in obstetrics and gynecology in the summer of 2015 or one of the approximately 1,300 US medical students who will apply to enter the field in 2016.

Medical students have a world of opportunity in front of them, with dozens of exciting career options. The fact that so many students select a career in our field is heartening. These students will become excellent obstetrician-gynecologistsand dedicate themselves to advancingthe health of the 150 million women in the United States. 
 

Would you select a career in obstetrics and gynecology again? Answer the Quick Poll on the home page and see how others have voted.

Why did you select a career in obstetrics and gynecology? Tell us at [email protected] Please include your name and city and state.

Case: Patient asks for transplantation referral
During an annual ObGyn visit, a 28-year-old G0 with congenital absence of the uterus excitedly tells you about the news report of the first birth following uterus transplantation. She always has dreamed of becoming pregnant, and this medical breakthrough has spurred her imagination of what might be. You ask if she would consider adoption or a gestational carrier. Responding that she prefers to carry her own pregnancy, she asks you to refer her to a uterus transplantation program. You promise to look into this option for her. As she opens the door to leave your office, she mentions that her mother has volunteered to be the uterus donor.

Later, you have misgivings about making a referral for uterus transplantation. You wonder: Is this procedure an appropriate use of health care resources? Do its risks outweigh the benefits?

In September 2014, a 36-year-old Swedish woman gave birth following uterus transplantation. A 61-year-old family friend donated the uterus for the procedure.¹ Prior to this breakthrough, women without a uterus had 3 reproductive alternatives: remain childless, adopt a child, or use a gestational carrier to give birth to their child. In many countries and some religions there are prohibitions against the use of a gestational carrier, leaving adoption as the only option to parenthood.

The first successful uterus transplantation did not occur by serendipity; a decade of careful work led to this breakthrough.^2–4 Remarkably, it is now proven that this type of transplantation can result in the successful birth of a baby—but at what cost?

The Brännström Uterus Transplantation Program: A medical breakthrough
Dr. Mats Brännström at the University of Gothenburg, Sweden, is the leader of the courageous and innovative team that developed the world’s first successful uterus transplantation program. The team required a broad range of expertise and skills and included physicians, scientists, and support staff from Sahlgrenska University Hospital and Stockholm IVF in Sweden; University of Valencia, Spain; Griffith University, Australia; and the Cleveland Clinic, Florida. Two recent publications report on the outcomes of the first 9 uterus transplants.^5,6

The successful protocol. The first step in the program is an exhaustive medical and psychosocial evaluation of the prospective uterus donor and recipient. Among the first 9 uterus recipients, 8 women had congenital absence of the uterus and 1 woman had a hysterectomy for cervical cancer. The uterus donors were mothers (in 5 cases), a mother-in-law, a sister, an aunt, and a friend.

After the recipient is approved for uterus transplantation, she undergoes in vitro fertilization (IVF) with cryopreservation of all embryos. IVF is recommended because it may not be possible to include the fallopian tubes in the uterus transplant or the tubes may not function properly following transplantation. The donor organ is harvested, using a modified radical hysterectomy with extended vascular pedicles, and transplanted into the pelvis of the recipient.

Following transplantation, immunosuppressive medications are prescribed daily to reduce the risk of organ rejection. The recipient is followed on a regular basis with physical examination and cervical biopsy to identify histologic markers of organ rejection. Episodes of rejection are treated with glucocorticoids and adjustment in the dose of immunosuppression medications. Fertility treatment with the recipient’s previously cryopreserved embryo begins 1 year following transplantation.

A unique feature of uterus transplantation is that the organ can be removed after childbearing is complete, thereby limiting lifetime exposure to immunosuppressive medications.

Uterus transplantation: Surgical folly?
Transplantation of a uterus involves major surgery. The inescapable reality is that the procedure will cause complications in some donors and recipients.

Specific complications faced. In the Brännström series, 1 uterus donor developed a postoperative ureterovaginal fistula, likely caused by extensive dissection of her ureters. This donor needed an additional operation to repair the fistula. Two of the 9 uterus transplants failed. One uterus was removed from the recipient 3 days after transplantation due to vascular occlusion and 1 uterus was removed 105 days after transplantation due to chronic infection resistant to antibiotic treatment. Seven of the transplants were successful and functioning in situ 12 months after transplantation as evidenced by regular menstrual bleeding. Five of the 7 recipients had rejection episodes, as demonstrated by the histology of cervix biopsies. Two of the recipients had 3 episodes of rejection. The rejection episodes were treated successfully with glucocorticoids and adjustment of immunosuppression medications.

Pregnancy in women with uterus transplantation is high risk because of the complications caused by immunosuppressive drugs and the high blood flow through the vascular grafts.^7–9 In the Brännström series, the agents utilized for immunosuppression included mycophenolate mofetil, azathioprine, tacrolimus, and glucocorticoids. Mycophenolate mofetil is a potent teratogen and routinely is discontinued prior to initiating attempts at pregnancy. Azathioprine is associated with an increased rate of congenital anomalies, but the benefits of this immunosuppressive are believed to outweigh the risks for most pregnant women with an organ transplant. Tacrolimus increases the risk of developing hypertension, preeclampsia, and intrauterine growth restriction during pregnancy.

In the Brännström case report, the woman who became pregnant following uterus transplantation took tacrolimus and azathioprine to prevent organ rejection both before and during her pregnancy. Not unexpectedly, she developed preeclampsia with severe features at 31 weeks and 5 days. After admission to the hospital, a worrisome fetal heart rate pattern developed and a cesarean delivery was performed. The newborn male weighed 1,775 g, and no congenital anomalies were observed. During pregnancy, blood flow to the uterus is in the range of 500 mL/min, the equivalent of 1 unit of whole blood per minute.¹⁰ This torrential pulsating flow may increase the risk of a vascular catastrophe such as the rupture of a major artery at one of the graft anastomoses, potentially causing the death of the fetus or mother. Much more experience will be needed to fully characterize the pattern of pregnancy complications that occurs following uterus transplantation.

The cost issue. Uterus transplantation is an extremely expensive medical procedure. In the United States each transplantation is likely to cost hundreds of thousands of dollars. Health care resources used to support uterus transplantation are not available for other pressing medical needs. Given that it is an experimental procedure, it is unlikely that health insurance will reimburse the costs of the medical care. Transplantation programs will need to seek major donors to support the costs, as was done in the Brännström program, or identify patients capable of paying for the transplant. If programs plan to have most patients pay for the procedure, bioethical concerns of equitable access and fair selection of recipients will need to be addressed.

Ethics. Uterus transplantation raises many bioethical concerns and programs need to engage biomedical ethicists to guide their activities.^11–13 Careful attention to thorough informed consent, risk-benefit analysis, equitable access, and fair selection of participants will be critical to running an ethical program. To reduce the risks of the procedure, programs likely will explore the use of uteri obtained from women who are brain dead or cadavers to spare altruistic living donors from undergoing hysterectomy surgery.

“Group of fools” or Nobel Prize in wait?
On December 23, 1954, the first successful kidney transplant was performed by Dr. Joseph E. ­Murray and his team at the Peter Bent Brigham Hospital, a predecessor to the Brigham and Women’s Hospital.¹⁴ His small group of physicians worked for years to perfect the kidney transplantation technique in the laboratory prior to attempting the case. A key to their success was the decision to perform the transplant with identical twins as the donor and recipient.

In the 1950s there was great controversy about whether kidney transplantation was a medical breakthrough or surgical folly. The lead surgical team was referred to as the “group of fools” by some colleagues. But Dr. Murray and his team succeeded in their efforts and opened the field of solid organ transplant. Recognizing the importance of his accomplishment, the Nobel Prize Committee awarded Dr. Murray the 1990 Nobel Prize in Physiology or Medicine. Dr. E. Donnell Thomas, a co-recipient of the award, was simultaneously recognized for developing bone marrow transplantation as a treatment for leukemia.

A medical breakthrough…
Organ transplantation medicine initially focused on the treatment of life-threatening diseases, including kidney, heart, lung, and liver failure. With recent innovations in composite tissue transplants, including face and limb, transplantation medicine is evolving to expand its focus to the repair of functional deficits that are not life threatening but do significantly impact quality of life. Uterus transplantation is an example of the new era of using transplants to repair functional deficits. The clinicians and patients involved in these innovative programs are courageous pioneers opening new vistas and helping to realize previously impossible dreams. In our time, many stakeholders are likely to conclude that uterus transplantation is a surgical folly. However, I predict that our children will conclude that uterus transplantation represents a medical breakthrough.

Share your thoughts on this article! Send your Letter to the Editor to  Please include your name and the city and state in which you practice.

Weigh in at the Quick Poll on the homepage. Send your answers to these cases and any comments to [email protected]. Please include your name and the city and state in which you practice.

Case: Patient asks for transplantation referral
During an annual ObGyn visit, a 28-year-old G0 with congenital absence of the uterus excitedly tells you about the news report of the first birth following uterus transplantation. She always has dreamed of becoming pregnant, and this medical breakthrough has spurred her imagination of what might be. You ask if she would consider adoption or a gestational carrier. Responding that she prefers to carry her own pregnancy, she asks you to refer her to a uterus transplantation program. You promise to look into this option for her. As she opens the door to leave your office, she mentions that her mother has volunteered to be the uterus donor.

Later, you have misgivings about making a referral for uterus transplantation. You wonder: Is this procedure an appropriate use of health care resources? Do its risks outweigh the benefits?

In September 2014, a 36-year-old Swedish woman gave birth following uterus transplantation. A 61-year-old family friend donated the uterus for the procedure.¹ Prior to this breakthrough, women without a uterus had 3 reproductive alternatives: remain childless, adopt a child, or use a gestational carrier to give birth to their child. In many countries and some religions there are prohibitions against the use of a gestational carrier, leaving adoption as the only option to parenthood.

The first successful uterus transplantation did not occur by serendipity; a decade of careful work led to this breakthrough.^2–4 Remarkably, it is now proven that this type of transplantation can result in the successful birth of a baby—but at what cost?

The Brännström Uterus Transplantation Program: A medical breakthrough
Dr. Mats Brännström at the University of Gothenburg, Sweden, is the leader of the courageous and innovative team that developed the world’s first successful uterus transplantation program. The team required a broad range of expertise and skills and included physicians, scientists, and support staff from Sahlgrenska University Hospital and Stockholm IVF in Sweden; University of Valencia, Spain; Griffith University, Australia; and the Cleveland Clinic, Florida. Two recent publications report on the outcomes of the first 9 uterus transplants.^5,6

The successful protocol. The first step in the program is an exhaustive medical and psychosocial evaluation of the prospective uterus donor and recipient. Among the first 9 uterus recipients, 8 women had congenital absence of the uterus and 1 woman had a hysterectomy for cervical cancer. The uterus donors were mothers (in 5 cases), a mother-in-law, a sister, an aunt, and a friend.

After the recipient is approved for uterus transplantation, she undergoes in vitro fertilization (IVF) with cryopreservation of all embryos. IVF is recommended because it may not be possible to include the fallopian tubes in the uterus transplant or the tubes may not function properly following transplantation. The donor organ is harvested, using a modified radical hysterectomy with extended vascular pedicles, and transplanted into the pelvis of the recipient.

Following transplantation, immunosuppressive medications are prescribed daily to reduce the risk of organ rejection. The recipient is followed on a regular basis with physical examination and cervical biopsy to identify histologic markers of organ rejection. Episodes of rejection are treated with glucocorticoids and adjustment in the dose of immunosuppression medications. Fertility treatment with the recipient’s previously cryopreserved embryo begins 1 year following transplantation.

A unique feature of uterus transplantation is that the organ can be removed after childbearing is complete, thereby limiting lifetime exposure to immunosuppressive medications.

Uterus transplantation: Surgical folly?
Transplantation of a uterus involves major surgery. The inescapable reality is that the procedure will cause complications in some donors and recipients.

Specific complications faced. In the Brännström series, 1 uterus donor developed a postoperative ureterovaginal fistula, likely caused by extensive dissection of her ureters. This donor needed an additional operation to repair the fistula. Two of the 9 uterus transplants failed. One uterus was removed from the recipient 3 days after transplantation due to vascular occlusion and 1 uterus was removed 105 days after transplantation due to chronic infection resistant to antibiotic treatment. Seven of the transplants were successful and functioning in situ 12 months after transplantation as evidenced by regular menstrual bleeding. Five of the 7 recipients had rejection episodes, as demonstrated by the histology of cervix biopsies. Two of the recipients had 3 episodes of rejection. The rejection episodes were treated successfully with glucocorticoids and adjustment of immunosuppression medications.

Pregnancy in women with uterus transplantation is high risk because of the complications caused by immunosuppressive drugs and the high blood flow through the vascular grafts.^7–9 In the Brännström series, the agents utilized for immunosuppression included mycophenolate mofetil, azathioprine, tacrolimus, and glucocorticoids. Mycophenolate mofetil is a potent teratogen and routinely is discontinued prior to initiating attempts at pregnancy. Azathioprine is associated with an increased rate of congenital anomalies, but the benefits of this immunosuppressive are believed to outweigh the risks for most pregnant women with an organ transplant. Tacrolimus increases the risk of developing hypertension, preeclampsia, and intrauterine growth restriction during pregnancy.

In the Brännström case report, the woman who became pregnant following uterus transplantation took tacrolimus and azathioprine to prevent organ rejection both before and during her pregnancy. Not unexpectedly, she developed preeclampsia with severe features at 31 weeks and 5 days. After admission to the hospital, a worrisome fetal heart rate pattern developed and a cesarean delivery was performed. The newborn male weighed 1,775 g, and no congenital anomalies were observed. During pregnancy, blood flow to the uterus is in the range of 500 mL/min, the equivalent of 1 unit of whole blood per minute.¹⁰ This torrential pulsating flow may increase the risk of a vascular catastrophe such as the rupture of a major artery at one of the graft anastomoses, potentially causing the death of the fetus or mother. Much more experience will be needed to fully characterize the pattern of pregnancy complications that occurs following uterus transplantation.

The cost issue. Uterus transplantation is an extremely expensive medical procedure. In the United States each transplantation is likely to cost hundreds of thousands of dollars. Health care resources used to support uterus transplantation are not available for other pressing medical needs. Given that it is an experimental procedure, it is unlikely that health insurance will reimburse the costs of the medical care. Transplantation programs will need to seek major donors to support the costs, as was done in the Brännström program, or identify patients capable of paying for the transplant. If programs plan to have most patients pay for the procedure, bioethical concerns of equitable access and fair selection of recipients will need to be addressed.

Ethics. Uterus transplantation raises many bioethical concerns and programs need to engage biomedical ethicists to guide their activities.^11–13 Careful attention to thorough informed consent, risk-benefit analysis, equitable access, and fair selection of participants will be critical to running an ethical program. To reduce the risks of the procedure, programs likely will explore the use of uteri obtained from women who are brain dead or cadavers to spare altruistic living donors from undergoing hysterectomy surgery.

“Group of fools” or Nobel Prize in wait?
On December 23, 1954, the first successful kidney transplant was performed by Dr. Joseph E. ­Murray and his team at the Peter Bent Brigham Hospital, a predecessor to the Brigham and Women’s Hospital.¹⁴ His small group of physicians worked for years to perfect the kidney transplantation technique in the laboratory prior to attempting the case. A key to their success was the decision to perform the transplant with identical twins as the donor and recipient.

In the 1950s there was great controversy about whether kidney transplantation was a medical breakthrough or surgical folly. The lead surgical team was referred to as the “group of fools” by some colleagues. But Dr. Murray and his team succeeded in their efforts and opened the field of solid organ transplant. Recognizing the importance of his accomplishment, the Nobel Prize Committee awarded Dr. Murray the 1990 Nobel Prize in Physiology or Medicine. Dr. E. Donnell Thomas, a co-recipient of the award, was simultaneously recognized for developing bone marrow transplantation as a treatment for leukemia.

A medical breakthrough…
Organ transplantation medicine initially focused on the treatment of life-threatening diseases, including kidney, heart, lung, and liver failure. With recent innovations in composite tissue transplants, including face and limb, transplantation medicine is evolving to expand its focus to the repair of functional deficits that are not life threatening but do significantly impact quality of life. Uterus transplantation is an example of the new era of using transplants to repair functional deficits. The clinicians and patients involved in these innovative programs are courageous pioneers opening new vistas and helping to realize previously impossible dreams. In our time, many stakeholders are likely to conclude that uterus transplantation is a surgical folly. However, I predict that our children will conclude that uterus transplantation represents a medical breakthrough.

Share your thoughts on this article! Send your Letter to the Editor to  Please include your name and the city and state in which you practice.

Weigh in at the Quick Poll on the homepage. Send your answers to these cases and any comments to [email protected]. Please include your name and the city and state in which you practice.

Case: Patient asks for transplantation referral
During an annual ObGyn visit, a 28-year-old G0 with congenital absence of the uterus excitedly tells you about the news report of the first birth following uterus transplantation. She always has dreamed of becoming pregnant, and this medical breakthrough has spurred her imagination of what might be. You ask if she would consider adoption or a gestational carrier. Responding that she prefers to carry her own pregnancy, she asks you to refer her to a uterus transplantation program. You promise to look into this option for her. As she opens the door to leave your office, she mentions that her mother has volunteered to be the uterus donor.

Later, you have misgivings about making a referral for uterus transplantation. You wonder: Is this procedure an appropriate use of health care resources? Do its risks outweigh the benefits?

In September 2014, a 36-year-old Swedish woman gave birth following uterus transplantation. A 61-year-old family friend donated the uterus for the procedure.¹ Prior to this breakthrough, women without a uterus had 3 reproductive alternatives: remain childless, adopt a child, or use a gestational carrier to give birth to their child. In many countries and some religions there are prohibitions against the use of a gestational carrier, leaving adoption as the only option to parenthood.

The first successful uterus transplantation did not occur by serendipity; a decade of careful work led to this breakthrough.^2–4 Remarkably, it is now proven that this type of transplantation can result in the successful birth of a baby—but at what cost?

The Brännström Uterus Transplantation Program: A medical breakthrough
Dr. Mats Brännström at the University of Gothenburg, Sweden, is the leader of the courageous and innovative team that developed the world’s first successful uterus transplantation program. The team required a broad range of expertise and skills and included physicians, scientists, and support staff from Sahlgrenska University Hospital and Stockholm IVF in Sweden; University of Valencia, Spain; Griffith University, Australia; and the Cleveland Clinic, Florida. Two recent publications report on the outcomes of the first 9 uterus transplants.^5,6

The successful protocol. The first step in the program is an exhaustive medical and psychosocial evaluation of the prospective uterus donor and recipient. Among the first 9 uterus recipients, 8 women had congenital absence of the uterus and 1 woman had a hysterectomy for cervical cancer. The uterus donors were mothers (in 5 cases), a mother-in-law, a sister, an aunt, and a friend.

After the recipient is approved for uterus transplantation, she undergoes in vitro fertilization (IVF) with cryopreservation of all embryos. IVF is recommended because it may not be possible to include the fallopian tubes in the uterus transplant or the tubes may not function properly following transplantation. The donor organ is harvested, using a modified radical hysterectomy with extended vascular pedicles, and transplanted into the pelvis of the recipient.

Following transplantation, immunosuppressive medications are prescribed daily to reduce the risk of organ rejection. The recipient is followed on a regular basis with physical examination and cervical biopsy to identify histologic markers of organ rejection. Episodes of rejection are treated with glucocorticoids and adjustment in the dose of immunosuppression medications. Fertility treatment with the recipient’s previously cryopreserved embryo begins 1 year following transplantation.

A unique feature of uterus transplantation is that the organ can be removed after childbearing is complete, thereby limiting lifetime exposure to immunosuppressive medications.

Uterus transplantation: Surgical folly?
Transplantation of a uterus involves major surgery. The inescapable reality is that the procedure will cause complications in some donors and recipients.

Specific complications faced. In the Brännström series, 1 uterus donor developed a postoperative ureterovaginal fistula, likely caused by extensive dissection of her ureters. This donor needed an additional operation to repair the fistula. Two of the 9 uterus transplants failed. One uterus was removed from the recipient 3 days after transplantation due to vascular occlusion and 1 uterus was removed 105 days after transplantation due to chronic infection resistant to antibiotic treatment. Seven of the transplants were successful and functioning in situ 12 months after transplantation as evidenced by regular menstrual bleeding. Five of the 7 recipients had rejection episodes, as demonstrated by the histology of cervix biopsies. Two of the recipients had 3 episodes of rejection. The rejection episodes were treated successfully with glucocorticoids and adjustment of immunosuppression medications.

Pregnancy in women with uterus transplantation is high risk because of the complications caused by immunosuppressive drugs and the high blood flow through the vascular grafts.^7–9 In the Brännström series, the agents utilized for immunosuppression included mycophenolate mofetil, azathioprine, tacrolimus, and glucocorticoids. Mycophenolate mofetil is a potent teratogen and routinely is discontinued prior to initiating attempts at pregnancy. Azathioprine is associated with an increased rate of congenital anomalies, but the benefits of this immunosuppressive are believed to outweigh the risks for most pregnant women with an organ transplant. Tacrolimus increases the risk of developing hypertension, preeclampsia, and intrauterine growth restriction during pregnancy.

In the Brännström case report, the woman who became pregnant following uterus transplantation took tacrolimus and azathioprine to prevent organ rejection both before and during her pregnancy. Not unexpectedly, she developed preeclampsia with severe features at 31 weeks and 5 days. After admission to the hospital, a worrisome fetal heart rate pattern developed and a cesarean delivery was performed. The newborn male weighed 1,775 g, and no congenital anomalies were observed. During pregnancy, blood flow to the uterus is in the range of 500 mL/min, the equivalent of 1 unit of whole blood per minute.¹⁰ This torrential pulsating flow may increase the risk of a vascular catastrophe such as the rupture of a major artery at one of the graft anastomoses, potentially causing the death of the fetus or mother. Much more experience will be needed to fully characterize the pattern of pregnancy complications that occurs following uterus transplantation.

The cost issue. Uterus transplantation is an extremely expensive medical procedure. In the United States each transplantation is likely to cost hundreds of thousands of dollars. Health care resources used to support uterus transplantation are not available for other pressing medical needs. Given that it is an experimental procedure, it is unlikely that health insurance will reimburse the costs of the medical care. Transplantation programs will need to seek major donors to support the costs, as was done in the Brännström program, or identify patients capable of paying for the transplant. If programs plan to have most patients pay for the procedure, bioethical concerns of equitable access and fair selection of recipients will need to be addressed.

Ethics. Uterus transplantation raises many bioethical concerns and programs need to engage biomedical ethicists to guide their activities.^11–13 Careful attention to thorough informed consent, risk-benefit analysis, equitable access, and fair selection of participants will be critical to running an ethical program. To reduce the risks of the procedure, programs likely will explore the use of uteri obtained from women who are brain dead or cadavers to spare altruistic living donors from undergoing hysterectomy surgery.

“Group of fools” or Nobel Prize in wait?
On December 23, 1954, the first successful kidney transplant was performed by Dr. Joseph E. ­Murray and his team at the Peter Bent Brigham Hospital, a predecessor to the Brigham and Women’s Hospital.¹⁴ His small group of physicians worked for years to perfect the kidney transplantation technique in the laboratory prior to attempting the case. A key to their success was the decision to perform the transplant with identical twins as the donor and recipient.

In the 1950s there was great controversy about whether kidney transplantation was a medical breakthrough or surgical folly. The lead surgical team was referred to as the “group of fools” by some colleagues. But Dr. Murray and his team succeeded in their efforts and opened the field of solid organ transplant. Recognizing the importance of his accomplishment, the Nobel Prize Committee awarded Dr. Murray the 1990 Nobel Prize in Physiology or Medicine. Dr. E. Donnell Thomas, a co-recipient of the award, was simultaneously recognized for developing bone marrow transplantation as a treatment for leukemia.

A medical breakthrough…
Organ transplantation medicine initially focused on the treatment of life-threatening diseases, including kidney, heart, lung, and liver failure. With recent innovations in composite tissue transplants, including face and limb, transplantation medicine is evolving to expand its focus to the repair of functional deficits that are not life threatening but do significantly impact quality of life. Uterus transplantation is an example of the new era of using transplants to repair functional deficits. The clinicians and patients involved in these innovative programs are courageous pioneers opening new vistas and helping to realize previously impossible dreams. In our time, many stakeholders are likely to conclude that uterus transplantation is a surgical folly. However, I predict that our children will conclude that uterus transplantation represents a medical breakthrough.

Share your thoughts on this article! Send your Letter to the Editor to  Please include your name and the city and state in which you practice.

Weigh in at the Quick Poll on the homepage. Send your answers to these cases and any comments to [email protected]. Please include your name and the city and state in which you practice.

Wright and colleagues analyzed the risk of diagnosing an occult uterine cancer at the time of myomectomy using an administrative database, which contained information on 41,777 myomectomy surgeries performed at 496 hospitals from 2006 to 2012. They reported that 76 uterine corpus cancers (ICD-9 codes 179.x and 182.x) were detected, for a rate of 1 occult cancer identified per 550 myomectomy cases. The risk of diagnosing an occult uterine cancer increased with age.

Study limitations
A major weakness of the study is that the administrative database did not provide information about the histologic type of uterine corpus cancer. Uterine leiomyosarcoma is a highly aggressive cancer, while endometrial stromal sarcoma is a more indolent cancer. Additionally, the authors were not able to perform a histologic reassessment of the slides of the 76 cases reported as having uterine corpus cancer in order to confirm the diagnosis. Although the investigators provide age-specific information about the risk of uterine cancer, they did not have information on the menopausal status of the women.

Strengths of the study
Prior to these study results there were few data about the risk of diagnosing an occult cancer at the time of myomectomy. This very large study of more than 41,000 myomectomy cases will help clinicians fully counsel women about the risk of detecting an occult uterine cancer at the time of myomectomy.

What this evidence means for practice
Women aged 50 years or older should be advised against having a myomectomy given the 1 in 154 and 1 in 31 risk of identifying an occult uterine corpus cancer at the time of surgery in women aged 50 to 59 years and 60 years or older, respectively. Given an average age of menopause of 51 years, these data support the guidance of the US Food and Drug Administration that open electric power morcellation should not be used in surgery on uterine tumors in women who are perimenopausal or postmenopausal.
–Robert L. Barbieri, MD

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Wright and colleagues analyzed the risk of diagnosing an occult uterine cancer at the time of myomectomy using an administrative database, which contained information on 41,777 myomectomy surgeries performed at 496 hospitals from 2006 to 2012. They reported that 76 uterine corpus cancers (ICD-9 codes 179.x and 182.x) were detected, for a rate of 1 occult cancer identified per 550 myomectomy cases. The risk of diagnosing an occult uterine cancer increased with age.

Study limitations
A major weakness of the study is that the administrative database did not provide information about the histologic type of uterine corpus cancer. Uterine leiomyosarcoma is a highly aggressive cancer, while endometrial stromal sarcoma is a more indolent cancer. Additionally, the authors were not able to perform a histologic reassessment of the slides of the 76 cases reported as having uterine corpus cancer in order to confirm the diagnosis. Although the investigators provide age-specific information about the risk of uterine cancer, they did not have information on the menopausal status of the women.

Strengths of the study
Prior to these study results there were few data about the risk of diagnosing an occult cancer at the time of myomectomy. This very large study of more than 41,000 myomectomy cases will help clinicians fully counsel women about the risk of detecting an occult uterine cancer at the time of myomectomy.

What this evidence means for practice
Women aged 50 years or older should be advised against having a myomectomy given the 1 in 154 and 1 in 31 risk of identifying an occult uterine corpus cancer at the time of surgery in women aged 50 to 59 years and 60 years or older, respectively. Given an average age of menopause of 51 years, these data support the guidance of the US Food and Drug Administration that open electric power morcellation should not be used in surgery on uterine tumors in women who are perimenopausal or postmenopausal.
–Robert L. Barbieri, MD

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Wright and colleagues analyzed the risk of diagnosing an occult uterine cancer at the time of myomectomy using an administrative database, which contained information on 41,777 myomectomy surgeries performed at 496 hospitals from 2006 to 2012. They reported that 76 uterine corpus cancers (ICD-9 codes 179.x and 182.x) were detected, for a rate of 1 occult cancer identified per 550 myomectomy cases. The risk of diagnosing an occult uterine cancer increased with age.

Study limitations
A major weakness of the study is that the administrative database did not provide information about the histologic type of uterine corpus cancer. Uterine leiomyosarcoma is a highly aggressive cancer, while endometrial stromal sarcoma is a more indolent cancer. Additionally, the authors were not able to perform a histologic reassessment of the slides of the 76 cases reported as having uterine corpus cancer in order to confirm the diagnosis. Although the investigators provide age-specific information about the risk of uterine cancer, they did not have information on the menopausal status of the women.

Strengths of the study
Prior to these study results there were few data about the risk of diagnosing an occult cancer at the time of myomectomy. This very large study of more than 41,000 myomectomy cases will help clinicians fully counsel women about the risk of detecting an occult uterine cancer at the time of myomectomy.

What this evidence means for practice
Women aged 50 years or older should be advised against having a myomectomy given the 1 in 154 and 1 in 31 risk of identifying an occult uterine corpus cancer at the time of surgery in women aged 50 to 59 years and 60 years or older, respectively. Given an average age of menopause of 51 years, these data support the guidance of the US Food and Drug Administration that open electric power morcellation should not be used in surgery on uterine tumors in women who are perimenopausal or postmenopausal.
–Robert L. Barbieri, MD

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.