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How should you evaluate a patient who has a cytologic diagnosis of atypical glandular cells (AGC)?
AGC is a relatively uncommon cytologic finding, with a mean reporting rate in 2003 of just 0.4% in the United States, according to guidelines from the ASCCP, the society for lower genital tract disease.1
“Although AGC is frequently caused by benign conditions, such as reactive changes and polyps, clinicians should be aware that it is not uncommon for AGC to be associated with a significant underlying neoplastic condition, including adenocarcinomas of the cervix, endometrium, ovary, and fallopian tube. Recent series have reported that 9%–38% of women with AGC have significant neoplasia…and 3%–17% have invasive cancer,” the guidelines state.1
In recent years, evidence-based guidelines such as this one have helped clinicians improve the care that they offer to their patients. Nevertheless, the cytologic diagnosis of AGC presents a dilemma. The significant rate of neoplasia associated with this finding, combined with the lack of sensitivity of methods of evaluation, is responsible for this quandary. Although clinicians try to avoid over-testing, there is a real concern about missing a critical diagnosis.
As ASCCP guidelines point out, all of the diagnostic testing done to investigate this cytologic finding lack sensitivity.1 This observation led to the recommendation that multiple modalities be combined in the evaluation of these patients.1 Previously published data suggest that women with AGC cytology are under-managed in both their initial and secondary evaluations.2
Authors explore management in women found to have cancer
Cheng and colleagues report on a large series of women who had a first-time diagnosis of AGC. These patients were drawn from an extensive, heterogeneous screening population in Taiwan. The report focuses only on patients who were ultimately found to have a diagnosis of invasive cancer—not those who had premalignant conditions such as cervical intraepithelial neoplasia (CIN) 2, CIN 3, adenocarcinoma in situ, or endometrial hyperplasia. The study confirms a high relative risk (RR) of gynecologic malignancy among women with a cytologic finding of AGC. The greatest risk is cervical cancer (RR, 17.85), followed by uterine cancer (RR, 5.68) and ovarian cancer (RR, 2.04).
Should we include US imaging in our assessment?
Current guidelines recommend colposcopy, endocervical curettage, cervical biopsy, and human papillomavirus (HPV) DNA testing (for high-risk types only) in women who have AGC. They also call for endometrial assessment among women at risk of uterine malignancy, including all women older than 35 years and those younger than 35 who have risk factors, such as unexplained vaginal bleeding, or a condition that suggests chronic anovulation.
Cheng and colleagues also include a recommendation for US imaging in women who have AGC, because of the risk of ovarian cancer. However, although the relative risk of ovarian cancer is roughly doubled among women who have AGC, compared with women with normal cytology, the absolute risk remains quite low. In this sample of 8,281 patients, for example, there were only 12 cases (0.14%).
Nor do the data presented by Cheng and colleagues make a compelling case for the addition of routine US in these patients. However, based on the results of this study, it may be prudent to consider US in certain risk groups when evaluation of the cervix and uterus is negative, such as women who have a family history of ovarian cancer, women who have breast cancer, or women who have a cytologic finding of adenocarcinoma.
HPV DNA testing was not included in this study
The authors suggest, instead, that this modality could be used for triage. However, both of the studies they cite to back this recommendation precede the 2006 ASCCP guidelines, which recommend testing for high-risk HPV types as part of the initial evaluation of women who have AGC but advise against using HPV DNA testing for triage.
More recent studies have confirmed that the sensitivity of HPV DNA testing is only approximately 80%, which is not sufficient for triage in this population.3 Such testing may reassure clinicians—but only after complete evaluation of the cervix and uterus. It can be used to guide subsequent surveillance after diagnostic studies, however.
We should adhere to ASCCP guidelines for the management of women who have AGC cytology, by performing:
- colposcopy with endocervical sampling in all women with this designation
- endometrial sampling in women 35 years and older and in women younger than 35 who have unexplained vaginal bleeding, chronic anovulation, or other clinical indications suggesting that they have a heightened risk of neoplastic endometrial lesions
- HPV DNA testing at the time of colposcopy.
As we mentioned, pelvic ultrasonography may be advisable if the patient has certain risk factors for ovarian cancer, such as a family history of ovarian malignancy, age older than 60 years, persistent AGC, or a cytologic finding of adenocarcinoma without uterine or cervical origin.
Compliance with these guidelines will reduce the risk of a missed diagnosis of neoplasia or cancer without excessive testing.
Women who have persistent AGC despite a negative comprehensive evaluation may be at increased risk of clinically significant disease. Clinicians should be aware of the guidelines for these women, which include the need for excisional biopsies and endometrial evaluation.4—Charles J. Dunton, MD, and Norman A. Brest, MD
We want to hear from you! Tell us what you think.
1. Wright TC, Jr, Massad LS, Dunton CJ, Spitzer M, Wilkinson EJ, Solomon D. 2006 Amercian Society for Colposcopy and Cervical Pathology-sponsored Consensus Conference 2006 consensus guidelines for the management of women with abnormal cervical cancer screening tests. Am J Obstet Gynecol. 2007;197(4):346-355.
2. Sharpless KE, Schnatz PF, Mandavilli S, Greene JF, Sorosky JI. Lack of adherence to practice guidelines for women with atypical glandular cells on cervical cytology. Obstet Gynecol. 2005;105(3):501-506.
3. Schnatz PF, Sharpless KE, O’Sullivan DM. Use of human papillomavirus testing in the management of atypical glandular cells. J Low Genit Tract Dis. 2009;13(2):94-101.
4. Dunton CJ. Management of atypical glandular cells and adenocarcinoma in situ. Obstet Gynecol Clin North Am. 2008;35(4):623-632.
AGC is a relatively uncommon cytologic finding, with a mean reporting rate in 2003 of just 0.4% in the United States, according to guidelines from the ASCCP, the society for lower genital tract disease.1
“Although AGC is frequently caused by benign conditions, such as reactive changes and polyps, clinicians should be aware that it is not uncommon for AGC to be associated with a significant underlying neoplastic condition, including adenocarcinomas of the cervix, endometrium, ovary, and fallopian tube. Recent series have reported that 9%–38% of women with AGC have significant neoplasia…and 3%–17% have invasive cancer,” the guidelines state.1
In recent years, evidence-based guidelines such as this one have helped clinicians improve the care that they offer to their patients. Nevertheless, the cytologic diagnosis of AGC presents a dilemma. The significant rate of neoplasia associated with this finding, combined with the lack of sensitivity of methods of evaluation, is responsible for this quandary. Although clinicians try to avoid over-testing, there is a real concern about missing a critical diagnosis.
As ASCCP guidelines point out, all of the diagnostic testing done to investigate this cytologic finding lack sensitivity.1 This observation led to the recommendation that multiple modalities be combined in the evaluation of these patients.1 Previously published data suggest that women with AGC cytology are under-managed in both their initial and secondary evaluations.2
Authors explore management in women found to have cancer
Cheng and colleagues report on a large series of women who had a first-time diagnosis of AGC. These patients were drawn from an extensive, heterogeneous screening population in Taiwan. The report focuses only on patients who were ultimately found to have a diagnosis of invasive cancer—not those who had premalignant conditions such as cervical intraepithelial neoplasia (CIN) 2, CIN 3, adenocarcinoma in situ, or endometrial hyperplasia. The study confirms a high relative risk (RR) of gynecologic malignancy among women with a cytologic finding of AGC. The greatest risk is cervical cancer (RR, 17.85), followed by uterine cancer (RR, 5.68) and ovarian cancer (RR, 2.04).
Should we include US imaging in our assessment?
Current guidelines recommend colposcopy, endocervical curettage, cervical biopsy, and human papillomavirus (HPV) DNA testing (for high-risk types only) in women who have AGC. They also call for endometrial assessment among women at risk of uterine malignancy, including all women older than 35 years and those younger than 35 who have risk factors, such as unexplained vaginal bleeding, or a condition that suggests chronic anovulation.
Cheng and colleagues also include a recommendation for US imaging in women who have AGC, because of the risk of ovarian cancer. However, although the relative risk of ovarian cancer is roughly doubled among women who have AGC, compared with women with normal cytology, the absolute risk remains quite low. In this sample of 8,281 patients, for example, there were only 12 cases (0.14%).
Nor do the data presented by Cheng and colleagues make a compelling case for the addition of routine US in these patients. However, based on the results of this study, it may be prudent to consider US in certain risk groups when evaluation of the cervix and uterus is negative, such as women who have a family history of ovarian cancer, women who have breast cancer, or women who have a cytologic finding of adenocarcinoma.
HPV DNA testing was not included in this study
The authors suggest, instead, that this modality could be used for triage. However, both of the studies they cite to back this recommendation precede the 2006 ASCCP guidelines, which recommend testing for high-risk HPV types as part of the initial evaluation of women who have AGC but advise against using HPV DNA testing for triage.
More recent studies have confirmed that the sensitivity of HPV DNA testing is only approximately 80%, which is not sufficient for triage in this population.3 Such testing may reassure clinicians—but only after complete evaluation of the cervix and uterus. It can be used to guide subsequent surveillance after diagnostic studies, however.
We should adhere to ASCCP guidelines for the management of women who have AGC cytology, by performing:
- colposcopy with endocervical sampling in all women with this designation
- endometrial sampling in women 35 years and older and in women younger than 35 who have unexplained vaginal bleeding, chronic anovulation, or other clinical indications suggesting that they have a heightened risk of neoplastic endometrial lesions
- HPV DNA testing at the time of colposcopy.
As we mentioned, pelvic ultrasonography may be advisable if the patient has certain risk factors for ovarian cancer, such as a family history of ovarian malignancy, age older than 60 years, persistent AGC, or a cytologic finding of adenocarcinoma without uterine or cervical origin.
Compliance with these guidelines will reduce the risk of a missed diagnosis of neoplasia or cancer without excessive testing.
Women who have persistent AGC despite a negative comprehensive evaluation may be at increased risk of clinically significant disease. Clinicians should be aware of the guidelines for these women, which include the need for excisional biopsies and endometrial evaluation.4—Charles J. Dunton, MD, and Norman A. Brest, MD
We want to hear from you! Tell us what you think.
AGC is a relatively uncommon cytologic finding, with a mean reporting rate in 2003 of just 0.4% in the United States, according to guidelines from the ASCCP, the society for lower genital tract disease.1
“Although AGC is frequently caused by benign conditions, such as reactive changes and polyps, clinicians should be aware that it is not uncommon for AGC to be associated with a significant underlying neoplastic condition, including adenocarcinomas of the cervix, endometrium, ovary, and fallopian tube. Recent series have reported that 9%–38% of women with AGC have significant neoplasia…and 3%–17% have invasive cancer,” the guidelines state.1
In recent years, evidence-based guidelines such as this one have helped clinicians improve the care that they offer to their patients. Nevertheless, the cytologic diagnosis of AGC presents a dilemma. The significant rate of neoplasia associated with this finding, combined with the lack of sensitivity of methods of evaluation, is responsible for this quandary. Although clinicians try to avoid over-testing, there is a real concern about missing a critical diagnosis.
As ASCCP guidelines point out, all of the diagnostic testing done to investigate this cytologic finding lack sensitivity.1 This observation led to the recommendation that multiple modalities be combined in the evaluation of these patients.1 Previously published data suggest that women with AGC cytology are under-managed in both their initial and secondary evaluations.2
Authors explore management in women found to have cancer
Cheng and colleagues report on a large series of women who had a first-time diagnosis of AGC. These patients were drawn from an extensive, heterogeneous screening population in Taiwan. The report focuses only on patients who were ultimately found to have a diagnosis of invasive cancer—not those who had premalignant conditions such as cervical intraepithelial neoplasia (CIN) 2, CIN 3, adenocarcinoma in situ, or endometrial hyperplasia. The study confirms a high relative risk (RR) of gynecologic malignancy among women with a cytologic finding of AGC. The greatest risk is cervical cancer (RR, 17.85), followed by uterine cancer (RR, 5.68) and ovarian cancer (RR, 2.04).
Should we include US imaging in our assessment?
Current guidelines recommend colposcopy, endocervical curettage, cervical biopsy, and human papillomavirus (HPV) DNA testing (for high-risk types only) in women who have AGC. They also call for endometrial assessment among women at risk of uterine malignancy, including all women older than 35 years and those younger than 35 who have risk factors, such as unexplained vaginal bleeding, or a condition that suggests chronic anovulation.
Cheng and colleagues also include a recommendation for US imaging in women who have AGC, because of the risk of ovarian cancer. However, although the relative risk of ovarian cancer is roughly doubled among women who have AGC, compared with women with normal cytology, the absolute risk remains quite low. In this sample of 8,281 patients, for example, there were only 12 cases (0.14%).
Nor do the data presented by Cheng and colleagues make a compelling case for the addition of routine US in these patients. However, based on the results of this study, it may be prudent to consider US in certain risk groups when evaluation of the cervix and uterus is negative, such as women who have a family history of ovarian cancer, women who have breast cancer, or women who have a cytologic finding of adenocarcinoma.
HPV DNA testing was not included in this study
The authors suggest, instead, that this modality could be used for triage. However, both of the studies they cite to back this recommendation precede the 2006 ASCCP guidelines, which recommend testing for high-risk HPV types as part of the initial evaluation of women who have AGC but advise against using HPV DNA testing for triage.
More recent studies have confirmed that the sensitivity of HPV DNA testing is only approximately 80%, which is not sufficient for triage in this population.3 Such testing may reassure clinicians—but only after complete evaluation of the cervix and uterus. It can be used to guide subsequent surveillance after diagnostic studies, however.
We should adhere to ASCCP guidelines for the management of women who have AGC cytology, by performing:
- colposcopy with endocervical sampling in all women with this designation
- endometrial sampling in women 35 years and older and in women younger than 35 who have unexplained vaginal bleeding, chronic anovulation, or other clinical indications suggesting that they have a heightened risk of neoplastic endometrial lesions
- HPV DNA testing at the time of colposcopy.
As we mentioned, pelvic ultrasonography may be advisable if the patient has certain risk factors for ovarian cancer, such as a family history of ovarian malignancy, age older than 60 years, persistent AGC, or a cytologic finding of adenocarcinoma without uterine or cervical origin.
Compliance with these guidelines will reduce the risk of a missed diagnosis of neoplasia or cancer without excessive testing.
Women who have persistent AGC despite a negative comprehensive evaluation may be at increased risk of clinically significant disease. Clinicians should be aware of the guidelines for these women, which include the need for excisional biopsies and endometrial evaluation.4—Charles J. Dunton, MD, and Norman A. Brest, MD
We want to hear from you! Tell us what you think.
1. Wright TC, Jr, Massad LS, Dunton CJ, Spitzer M, Wilkinson EJ, Solomon D. 2006 Amercian Society for Colposcopy and Cervical Pathology-sponsored Consensus Conference 2006 consensus guidelines for the management of women with abnormal cervical cancer screening tests. Am J Obstet Gynecol. 2007;197(4):346-355.
2. Sharpless KE, Schnatz PF, Mandavilli S, Greene JF, Sorosky JI. Lack of adherence to practice guidelines for women with atypical glandular cells on cervical cytology. Obstet Gynecol. 2005;105(3):501-506.
3. Schnatz PF, Sharpless KE, O’Sullivan DM. Use of human papillomavirus testing in the management of atypical glandular cells. J Low Genit Tract Dis. 2009;13(2):94-101.
4. Dunton CJ. Management of atypical glandular cells and adenocarcinoma in situ. Obstet Gynecol Clin North Am. 2008;35(4):623-632.
1. Wright TC, Jr, Massad LS, Dunton CJ, Spitzer M, Wilkinson EJ, Solomon D. 2006 Amercian Society for Colposcopy and Cervical Pathology-sponsored Consensus Conference 2006 consensus guidelines for the management of women with abnormal cervical cancer screening tests. Am J Obstet Gynecol. 2007;197(4):346-355.
2. Sharpless KE, Schnatz PF, Mandavilli S, Greene JF, Sorosky JI. Lack of adherence to practice guidelines for women with atypical glandular cells on cervical cytology. Obstet Gynecol. 2005;105(3):501-506.
3. Schnatz PF, Sharpless KE, O’Sullivan DM. Use of human papillomavirus testing in the management of atypical glandular cells. J Low Genit Tract Dis. 2009;13(2):94-101.
4. Dunton CJ. Management of atypical glandular cells and adenocarcinoma in situ. Obstet Gynecol Clin North Am. 2008;35(4):623-632.
Do women who have CIN 3 face an elevated risk of Ca after treatment?
Yes. This prospective cohort study from Sweden found a higher risk of invasive cervical cancer and vaginal cancer in women who had been treated for cervical intraepithelial neoplasia (CIN) 3. The study included all women in Sweden who were treated for severe dysplasia or cervical carcinoma in situ—equivalent to CIN 3—from 1958 to 2002, a total of 2,315,724 woman-years of follow-up. The standardized incidence ratio for invasive cervical cancer in women treated for CIN 3, compared with the general population, was 2.34 (95% confidence interval, 2.18–2.50). The relative risk of vaginal cancer also was high, exceeding 6. Women faced an even higher risk if they were older than 50 at treatment.
The risk of cancer decreased over time, but was still elevated 25 years after treatment.
EXPERT COMMENTARY
Newly updated consensus guidelines for posttreatment management of women with CIN 2,3 recommend human papillomavirus (HPV) testing at 6 to 12 months.1 Surveillance using cytology or a combination of cytology and colposcopy at 6-month intervals also is acceptable. Women who have a positive test should undergo colposcopy and endocervical sampling. Women who have a negative HPV test or two consecutive negative Pap tests after treatment should be screened annually for at least 20 years. These recommendations were based on data that showed a higher incidence of recurrent disease and invasive cancer in women previously treated for high-grade dysplasia. This excellent study by Strander and associates confirms those recommendations.
Women who were treated from 1991 to 2000 had a risk of cancer and neoplasia almost twice as high as that of women treated from 1958 to 1970. Excision procedures became the main treatment for dysplasia after 1980 (replacing hysterectomy). Increased prevalence of HPV infection also may have a greater effect on women who have been treated for CIN than on the general population, who may be more immune competent.
In this study, it was not possible to link cervical or vaginal cancers with the specific method of treatment of CIN 3
This study confirms recommendations of the 2006 Consensus Conference for long-term surveillance of women treated for CIN 3.1 Those recommendations are at odds, however, with guidelines issued by the American College of Obstetricians and Gynecologists, which state: “Women who have had a hysterectomy and have a history of CIN 2 or CIN 3—or in whom a negative history cannot be documented—should continue to be screened annually until three consecutive satisfactory negative cervical cytology results are obtained. Routine screening may then be discontinued.”2 It has been my practice to continue to screen women even after hysterectomy if they have a history of high-grade dysplasia. The American Cancer Society also recommends continued screening after hysterectomy in women who have been treated for cervical dysplasia or cancer.
1. Wright TC, Jr, Massad LS, Dunton CJ, Spitzer M, Wilkinson EJ, Soloman D. 2006 consensus guidelines for the management of women with cervical intraepithelial neoplasia or adenocarcinoma in situ. Am J Obstet Gynecol. 2007;197:340-345
2. Cervical Cytology Screening. Practice Bulletin No. 45. Washington, DC: ACOG; 2003.
Yes. This prospective cohort study from Sweden found a higher risk of invasive cervical cancer and vaginal cancer in women who had been treated for cervical intraepithelial neoplasia (CIN) 3. The study included all women in Sweden who were treated for severe dysplasia or cervical carcinoma in situ—equivalent to CIN 3—from 1958 to 2002, a total of 2,315,724 woman-years of follow-up. The standardized incidence ratio for invasive cervical cancer in women treated for CIN 3, compared with the general population, was 2.34 (95% confidence interval, 2.18–2.50). The relative risk of vaginal cancer also was high, exceeding 6. Women faced an even higher risk if they were older than 50 at treatment.
The risk of cancer decreased over time, but was still elevated 25 years after treatment.
EXPERT COMMENTARY
Newly updated consensus guidelines for posttreatment management of women with CIN 2,3 recommend human papillomavirus (HPV) testing at 6 to 12 months.1 Surveillance using cytology or a combination of cytology and colposcopy at 6-month intervals also is acceptable. Women who have a positive test should undergo colposcopy and endocervical sampling. Women who have a negative HPV test or two consecutive negative Pap tests after treatment should be screened annually for at least 20 years. These recommendations were based on data that showed a higher incidence of recurrent disease and invasive cancer in women previously treated for high-grade dysplasia. This excellent study by Strander and associates confirms those recommendations.
Women who were treated from 1991 to 2000 had a risk of cancer and neoplasia almost twice as high as that of women treated from 1958 to 1970. Excision procedures became the main treatment for dysplasia after 1980 (replacing hysterectomy). Increased prevalence of HPV infection also may have a greater effect on women who have been treated for CIN than on the general population, who may be more immune competent.
In this study, it was not possible to link cervical or vaginal cancers with the specific method of treatment of CIN 3
This study confirms recommendations of the 2006 Consensus Conference for long-term surveillance of women treated for CIN 3.1 Those recommendations are at odds, however, with guidelines issued by the American College of Obstetricians and Gynecologists, which state: “Women who have had a hysterectomy and have a history of CIN 2 or CIN 3—or in whom a negative history cannot be documented—should continue to be screened annually until three consecutive satisfactory negative cervical cytology results are obtained. Routine screening may then be discontinued.”2 It has been my practice to continue to screen women even after hysterectomy if they have a history of high-grade dysplasia. The American Cancer Society also recommends continued screening after hysterectomy in women who have been treated for cervical dysplasia or cancer.
Yes. This prospective cohort study from Sweden found a higher risk of invasive cervical cancer and vaginal cancer in women who had been treated for cervical intraepithelial neoplasia (CIN) 3. The study included all women in Sweden who were treated for severe dysplasia or cervical carcinoma in situ—equivalent to CIN 3—from 1958 to 2002, a total of 2,315,724 woman-years of follow-up. The standardized incidence ratio for invasive cervical cancer in women treated for CIN 3, compared with the general population, was 2.34 (95% confidence interval, 2.18–2.50). The relative risk of vaginal cancer also was high, exceeding 6. Women faced an even higher risk if they were older than 50 at treatment.
The risk of cancer decreased over time, but was still elevated 25 years after treatment.
EXPERT COMMENTARY
Newly updated consensus guidelines for posttreatment management of women with CIN 2,3 recommend human papillomavirus (HPV) testing at 6 to 12 months.1 Surveillance using cytology or a combination of cytology and colposcopy at 6-month intervals also is acceptable. Women who have a positive test should undergo colposcopy and endocervical sampling. Women who have a negative HPV test or two consecutive negative Pap tests after treatment should be screened annually for at least 20 years. These recommendations were based on data that showed a higher incidence of recurrent disease and invasive cancer in women previously treated for high-grade dysplasia. This excellent study by Strander and associates confirms those recommendations.
Women who were treated from 1991 to 2000 had a risk of cancer and neoplasia almost twice as high as that of women treated from 1958 to 1970. Excision procedures became the main treatment for dysplasia after 1980 (replacing hysterectomy). Increased prevalence of HPV infection also may have a greater effect on women who have been treated for CIN than on the general population, who may be more immune competent.
In this study, it was not possible to link cervical or vaginal cancers with the specific method of treatment of CIN 3
This study confirms recommendations of the 2006 Consensus Conference for long-term surveillance of women treated for CIN 3.1 Those recommendations are at odds, however, with guidelines issued by the American College of Obstetricians and Gynecologists, which state: “Women who have had a hysterectomy and have a history of CIN 2 or CIN 3—or in whom a negative history cannot be documented—should continue to be screened annually until three consecutive satisfactory negative cervical cytology results are obtained. Routine screening may then be discontinued.”2 It has been my practice to continue to screen women even after hysterectomy if they have a history of high-grade dysplasia. The American Cancer Society also recommends continued screening after hysterectomy in women who have been treated for cervical dysplasia or cancer.
1. Wright TC, Jr, Massad LS, Dunton CJ, Spitzer M, Wilkinson EJ, Soloman D. 2006 consensus guidelines for the management of women with cervical intraepithelial neoplasia or adenocarcinoma in situ. Am J Obstet Gynecol. 2007;197:340-345
2. Cervical Cytology Screening. Practice Bulletin No. 45. Washington, DC: ACOG; 2003.
1. Wright TC, Jr, Massad LS, Dunton CJ, Spitzer M, Wilkinson EJ, Soloman D. 2006 consensus guidelines for the management of women with cervical intraepithelial neoplasia or adenocarcinoma in situ. Am J Obstet Gynecol. 2007;197:340-345
2. Cervical Cytology Screening. Practice Bulletin No. 45. Washington, DC: ACOG; 2003.
Excisional biopsy for CIN
- In most cases, loop electrosurgical excision procedure (LEEP) and cold-knife conization (CKC) result in equivalent success rates and margin status.
- CKC is preferred in cases of adenocarcinoma in situ or squamous microinvasion.
- Conservative follow-up is generally possible in adenocarcinoma in situ and squamous microinvasion when margins are negative.
- Colposcopy, endocervical curettage, and biopsies should be part of the follow-up strategy for patients with positive margins.
When cervical intraepithelial neoplasia (CIN) requires treatment, loop electrosurgical excision procedure (LEEP) is the most frequently used modality, although cold-knife conization (CKC) of the cervical transformation zone still is preferred in select cases. Since excisional techniques are used with CKC, margin status is known and clinical decisions may be based on this information.
This article reviews current indications for excisional biopsy and presents evidence to direct management and follow-up of patients with positive and negative margins.
Selecting a technique
Several large randomized and prospective studies have demonstrated that LEEP is similar in efficacy to CKC and may even remove less of the normal cervical stroma.1-3 In general, LEEP is used to excise high-grade and recurrent squamous dysplasia, as it is similar to CKC in its rates of incomplete excision and residual disease.1,4 However, when adenocarcinoma in situ (AIS) is present, CKC is preferred for diagnosis and treatment, since it results in a lower incidence of involved margins and a lower recurrence rate.3,5-7
CKC also is preferred when histologic confirmation of the margin status is crucial, such as when invasion with squamous lesions is suspected. This is because thermal artifacts that may result from LEEP will interfere with interpretation, further complicating treatment planning.1,4,8,9 In cases of microinvasion, the ability to confirm margins makes conservative treatment possible; if the depth of invasion cannot be determined from the specimen, radical surgery may be necessary.
In the hands of an experienced clinician, however, thermal artifact from the LEEP technique generally is not a significant problem. Series reporting high rates of uninterpretable margins have been attributed to operator inexperience.10 In general, thermal artifact is reduced by limiting the number of sections taken. In ideal cases, only a single-piece specimen is obtained, similar to that achieved using CKC.8,10,11 Newer loops, such as the cone biopsy excision loop, may decrease the number of sections and further improve margin interpretation.8
I use CKC in cases of suspected squamous invasion and in the evaluation of glandular lesions, but feel that in other cases LEEP is efficacious and quicker.
Identifying residual disease
When both the endocervical margin and endocervical curettage (ECC) are positive for squamous dysplasia at the time of excision, there is an increased risk of residual disease (TABLE 1).12-14 However, it is not clear whether ECC alone is an independent predictor of residual disease. Although 1 study suggests an increased risk of invasive cancer in women over 50 years of age with a positive ECC at the time of conization, other series have failed to demonstrate a difference in treatment failure rates based on ECC.15-17 Thus, the utility of ECC in directing further therapy at the time of excisional biopsy is unclear. I generally do not perform an ECC with LEEP for squamous dysplasia.
In AIS, a positive ECC is a strong predictor of residual disease, while a negative ECC is of limited significance.18 I am more likely to perform an ECC with glandular lesions. If it is negative, close follow-up still is indicated. If it is positive, repeat excision may be necessary.
TABLE 1
Residual disease and margin status: squamous dysplasia
AUTHOR | PROPORTION WITH RESIDUAL DISEASE | |||
---|---|---|---|---|
NEGATIVE MARGINS | POSITIVE MARGINS | |||
NUMBER | % | NUMBER | % | |
SQUAMOUS LESIONS | ||||
Bertelsen et al, 199923 | 44/485 | 9 | 29/76 | 38.2 |
Moore et al, 199524 | 170/523 | 32.5 | 37/91 | 40.7 |
Lopes et al, 199325 | 0/176 | 0 | 11/131 | 8.4 |
Murdoch et al, 199226 | 7/405 | 1.7 | 22/160 | 13.8 |
Andersen et al, 199019 | 0/411 | 0 | 6/469 | 1.3 |
TOTALS | 221/2,000 | 11 | 105/927 | 11.3 |
SQUAMOUS MICROINVASION | ||||
Gurgel et al, 199727 | 6/74 | 8.1 | 45/76 | 59.2 |
Roman et al, 199722 | 1/30 | 3.3 | 7/50 | 14 |
TOTALS | 7/104 | 6.7 | 52/126 | 41.3 |
Follow-up of squamous lesions
Considerable clinical uncertainty remains over the relative strengths of cytologic, colposcopic, and histologic evaluation for residual or recurrent disease following excisional biopsy. Conservative management includes Papanicolaou smears alone or in combination with ECC and/or colposcopy.
Negative margins. If margins are negative, the success rate of excisional biopsy is high (90%-100%), and careful observation is the preferred follow-up. Repeat cytologic testing will identify the majority of patients with residual high-grade disease. A prospective randomized trial of cytologic surveillance showed that the detection rate was only 1.9% higher for histology.19 Although 1 report suggests that colposcopy can expedite the diagnosis of recurrent dysplasia, it is unclear from this report whether colposcopy identified significant high-grade dysplasia that cytology missed.20
Positive margins. In most series involving CIN with positive margins, treatment success rates do not differ significantly between patients who undergo repeat surgical procedures and those who have close follow-up. However, endocervical margin involvement appears to carry a higher treatment failure rate than ectocervical margin involvement. Data are conflicting on the proper method of conservative follow-up. Some authors propose only frequent cytologic testing, while others recommend that colposcopy be performed.19-21
For patients with positive margins, I perform both cytology and colposcopy in 4 to 6 months. If an endocervical margin was positive, I also perform an ECC. If this evaluation is negative, I repeat cytologic testing every 6 months until 3 consecutive Pap smears are normal and satisfactory. In cases of recurrent high-grade dysplasia with positive margins, hysterectomy may be indicated, depending on the patient’s age and desire for continued fertility.14,21
Squamous microinvasion
There is a significant risk (50%-80%) of residual disease or true invasion when margins or an ECC are positive and microinvasion is present.2,5-7 In these cases, a repeat excisional biopsy should be performed to determine the true extent of disease prior to deciding on definitive therapy.22 As previously mentioned, CKC is preferred to limit artifact that could obscure interpretation. If the patient has completed her childbearing, hysterectomy remains the standard treatment for microinvasive squamous cell carcinoma. When the woman wishes to preserve fertility, conservative follow-up appears to be safe if the final pathologic specimen has negative margins. A follow-up protocol including cytologic, colposcopic, and ECC monitoring in the first post-conization visit is recommended.2,6
Glandular lesions
AIS with involved margins requires further surgery due to the possibility of residual AIS or invasion (TABLES 2 and 3).2,5-7 In these cases, CKC is preferable to LEEP.3,5-7 Hysterectomy remains the standard therapy for AIS. Conservative management is an option if fertility is desired and margin status is negative. Patients should be informed that persistent disease or recurrence is possible and that there is a risk of invasive disease.15
Counseling, thorough documentation, and second surgical and pathologic opinions may be helpful in conservative management. Colposcopy, ECC, and cytology are indicated at the first follow-up visit, with cytology repeated every 6 months until 4 consecutive Paps are normal. More frequent colposcopy and liberal use of ECC also may be considered.
TABLE 2
Residual disease and margin status: adenocarcinoma in situ
AUTHOR | PROPORTION WITH RESIDUAL DISEASE | |||
---|---|---|---|---|
NEGATIVE MARGINS | POSITIVE MARGINS | |||
NUMBER | % | NUMBER | % | |
Azodi et al, 199928 | 5/16 | 31.3 | 9/16 | 56.3 |
Goldstein et al, 199828 | 13/43 | 30.2 | 8/18 | 44.4 |
Denehy et al, 19976 | 2/7 | 28.6 | 7/10 | 70 |
Widrich et al, 19965 | 0/3 | 0 | 9/14 | 64.3 |
Wolf et al, 199629 | 7/21 | 33.3 | 10/19 | 52.6 |
TOTAL | 27/90 | 30 | 43/77 | 55.8 |
TABLE 3
Follow-up recommendations
Pathology | Margin status | Recommendation |
---|---|---|
High-grade squamous lesion | Negative |
|
Positive, endocervical |
| |
Positive, ectocervical |
| |
Squamous microinvasion | Negative, fertility desired |
|
Negative, no desire for fertility | Hysterectomy | |
Positive | CKC | |
Adenocarcinoma in situ | Negative, fertility desired |
|
Negative, no desire for fertility | Hysterectomy | |
Positive | CKC | |
CKC = cold-knife conization; ECC = endocervical curettage |
When further excision is necessary
As noted earlier, repeat excision is necessary in cases of squamous microinvasion or AIS with positive margins. CKC is generally preferred to allow for optimal pathologic interpretation. For squamous intraepithelial lesions, excisional biopsy with close follow-up has a significant cure rate, and hysterectomy usually is not indicated. However, hysterectomy still should be considered part of the treatment continuum for CIN, particularly for patients who have completed childbearing.
Conclusion
Although the risk of recurrence is correlated with a patient’s margin status in cases of squamous dysplasia, conservative follow-up is possible and has a high success rate. Cytology is sufficient surveillance for cases involving negative margins. When margins are positive, colposcopy and ECC also may be useful. Microinvasive lesions with positive margins require further surgical evaluation to determine treatment. For glandular lesions, CKC is preferred for both diagnosis and treatment.
Dr. Dunton reports no affiliation or financial arrangement with any of the companies that manufacture drugs or devices in any of the product classes mentioned in this article.
1. Mathevet P, Dargent D, Roy M, Beau G. A randomized prospective study comparing three techniques of conization: cold knife, laser, and LEEP. Gynecol Oncol. 1994;54(2):175-179.
2. Duggan BD, Felix JC, Muderspach LI, et al. Cold-knife conization versus conization by the loop electrosurgical excision procedure: a randomized, prospective study. Am J Obstet Gynecol. 1999;180:276-282.
3. Girardi F, Heydarfadi M, Koroschetz F, et al. Cold-knife conization versus loop excision: histopathologic and clinical results of a randomized trial. Gynecol Oncol. 1994;55:368-370.
4. Gold M, Dunton CJ, Murray J, et al. Loop electrocautery excisional procedure: therapeutic effectiveness as an ablation and a conization equivalent. Gynecol Oncol. 1996;61:241-244.
5. Widrich T, Kennedy AW, Myers TM, et al. Adenocarcinoma in situ of the uterine cervix: management and outcome. Gynecol Oncol. 1996;61:304-308.
6. Denehy TR, Gregori CA, Breen JL. Endocervical curettage, cone margins, and residual adenocarcinoma in situ of the cervix. Obstet Gynecol. 1997;90:1-6.
7. Muntz HG, Bell DA, Lage JM, et al. Adenocarcinoma in situ of the uterine cervix. Obstet Gynecol. 1992;80:935-939.
8. Naumann RW, Bell MC, Alvarez RD, et al. LLETZ is an acceptable alternative to diagnostic cold-knife conization. Gynecol Oncol. 1994;55:224-228.
9. Eddy GL, Spiegel GW, Creasman WT. Adverse effect of electrosurgical loop excision on assignment of FIGO stage in cervical cancer: report of two cases. Gynecol Oncol. 1994;55:313-317.
10. Montz FJ, Holschneider CH, Thompson LDR. Large-loop excision of the transformation zone: effect on the pathologic interpretation of resection margins. Obstet Gynecol. 1993;81:976-982.
11. Gardeil F, Barry-Walsh C, Prendiville W, et al. Persistent intraepithelial neoplasia after excision for cervical intraepithelial neoplasia grade III. Obstet Gynecol. 1987;89:419-422.
12. Felix JC, Muderspach LI, Duggan BD, Roman LD. The significance of positive margins in loop electrosurgical cone biopsies. Obstet Gynecol. 1994;84:996-1000.
13. Kobak WH, Roman LD, Felix JC, et al. The role of endocervical curettage at cervical conization for high-grade dysplasia. Obstet Gynecol. 1995;85:197-201.
14. Husseinzadeh N, Shbara I, Wessler T. Predictive value of cone margins and post-cone endocervical curettage with residual disease in subsequent hysterectomy. Gynecol Oncol. 1989;33:198-200.
15. Poyner EA, Barakat RR, Hoskins WJ. Management and follow-up of patients with adenocarcinoma in situ of the uterine cervix. Gynecol Oncol. 1995;57:158-164.
16. Frauchiger WL, De Frias DVS, Cajulis RS, Yu GH. The immediate postconization endocervical smear: evaluation of its utility in the detection of residual dysplasia. Acta Cytol. 1998;42:1139-1143.
17. Wright TC, Gagnon S, Richart RM, Ferenczy A. Treatment of cervical intraepithelial neoplasia using the loop electrosurgical excision procedure. Obstet Gynecol. 1992;79:173-178.
18. Goldstein NS, Mani A. The status and distance of cone biopsy margins as a predictor of excision adequacy for endocervical adenocarcinoma in situ. Am J Clin Pathol. 1998;109:727-732.
19. Andersen ES, Nielsen K, Larsen G. Laser conization: follow-up in patients with cervical intraepithelial neoplasia in the cone margin. Gynecol Oncol. 1990;39:328-331.
20. Paraskevaidis E, Jandial L, Mann EMF, Fisher PM. Pattern of treatment failure following laser for cervical intraepithelial neoplasia: implications for follow-up protocol. Obstet Gynecol. 1991;78:80-83.
21. Lapaquette TK, Dinh TV, Hannigan EV, et al. Management of patients with positive margins after cervical conization. Obstet Gynecol. 1993;82:440-443.
22. Roman LD, Felix JC, Muderspach LI, et al. Risk of residual invasive disease in women with microinvasive squamous cancer in a conization specimen. Obstet Gynecol. 1997;90:759-764.
23. Bertelsen B, Tande T, Sandvei, Hartveit F. Laser conization of cervical intraepithelial neoplasia grade 3. Acta Obstet Gynecol Scand. 1999;78:54-59.
24. Moore BC, Higgins RV, Laurent SL, et al. Predictive factors from cold knife conization for residual cervical intraepithelial neoplasia in subsequent hysterectomy. Am J Obstet Gynecol. 1995;173:361-368.
25. Lopes A, Morgan P, Murdoch J, et al. The case for conservative management of “incomplete excision” of CIN after laser conization. Gynecol Oncol. 1993;49:247-249.
26. Murdoch JB, Morgan PR, Lopes A, Monaghan JM. Histological incomplete excision of CIN after large loop excision of the transformation zone (LLETZ) merits careful follow up, not retreatment. Br J Obstet Gynaecol. 1992;99:990-993.
27. Gurgel MSC, Bedone AJ, Andrade LA, et al. Microinvasive carcinoma of the uterine cervix: histological findings on cone specimens related to residual neoplasia on hysterectomy. Gynecol Oncol. 1997;65:437-440.
28. Azodi M, Chambers SK, Rutherford TJ, et al. Adenocarcinoma in situ of the cervix: management and outcome. Gynecol Oncol. 1999;73:348-353.
29. Wolf JK, Levenback C, Malpica A, et al. Adenocarcinoma in situ of the cervix: significance of cone biopsy margins. Obstet Gynecol. 1996;88:82-86.
- In most cases, loop electrosurgical excision procedure (LEEP) and cold-knife conization (CKC) result in equivalent success rates and margin status.
- CKC is preferred in cases of adenocarcinoma in situ or squamous microinvasion.
- Conservative follow-up is generally possible in adenocarcinoma in situ and squamous microinvasion when margins are negative.
- Colposcopy, endocervical curettage, and biopsies should be part of the follow-up strategy for patients with positive margins.
When cervical intraepithelial neoplasia (CIN) requires treatment, loop electrosurgical excision procedure (LEEP) is the most frequently used modality, although cold-knife conization (CKC) of the cervical transformation zone still is preferred in select cases. Since excisional techniques are used with CKC, margin status is known and clinical decisions may be based on this information.
This article reviews current indications for excisional biopsy and presents evidence to direct management and follow-up of patients with positive and negative margins.
Selecting a technique
Several large randomized and prospective studies have demonstrated that LEEP is similar in efficacy to CKC and may even remove less of the normal cervical stroma.1-3 In general, LEEP is used to excise high-grade and recurrent squamous dysplasia, as it is similar to CKC in its rates of incomplete excision and residual disease.1,4 However, when adenocarcinoma in situ (AIS) is present, CKC is preferred for diagnosis and treatment, since it results in a lower incidence of involved margins and a lower recurrence rate.3,5-7
CKC also is preferred when histologic confirmation of the margin status is crucial, such as when invasion with squamous lesions is suspected. This is because thermal artifacts that may result from LEEP will interfere with interpretation, further complicating treatment planning.1,4,8,9 In cases of microinvasion, the ability to confirm margins makes conservative treatment possible; if the depth of invasion cannot be determined from the specimen, radical surgery may be necessary.
In the hands of an experienced clinician, however, thermal artifact from the LEEP technique generally is not a significant problem. Series reporting high rates of uninterpretable margins have been attributed to operator inexperience.10 In general, thermal artifact is reduced by limiting the number of sections taken. In ideal cases, only a single-piece specimen is obtained, similar to that achieved using CKC.8,10,11 Newer loops, such as the cone biopsy excision loop, may decrease the number of sections and further improve margin interpretation.8
I use CKC in cases of suspected squamous invasion and in the evaluation of glandular lesions, but feel that in other cases LEEP is efficacious and quicker.
Identifying residual disease
When both the endocervical margin and endocervical curettage (ECC) are positive for squamous dysplasia at the time of excision, there is an increased risk of residual disease (TABLE 1).12-14 However, it is not clear whether ECC alone is an independent predictor of residual disease. Although 1 study suggests an increased risk of invasive cancer in women over 50 years of age with a positive ECC at the time of conization, other series have failed to demonstrate a difference in treatment failure rates based on ECC.15-17 Thus, the utility of ECC in directing further therapy at the time of excisional biopsy is unclear. I generally do not perform an ECC with LEEP for squamous dysplasia.
In AIS, a positive ECC is a strong predictor of residual disease, while a negative ECC is of limited significance.18 I am more likely to perform an ECC with glandular lesions. If it is negative, close follow-up still is indicated. If it is positive, repeat excision may be necessary.
TABLE 1
Residual disease and margin status: squamous dysplasia
AUTHOR | PROPORTION WITH RESIDUAL DISEASE | |||
---|---|---|---|---|
NEGATIVE MARGINS | POSITIVE MARGINS | |||
NUMBER | % | NUMBER | % | |
SQUAMOUS LESIONS | ||||
Bertelsen et al, 199923 | 44/485 | 9 | 29/76 | 38.2 |
Moore et al, 199524 | 170/523 | 32.5 | 37/91 | 40.7 |
Lopes et al, 199325 | 0/176 | 0 | 11/131 | 8.4 |
Murdoch et al, 199226 | 7/405 | 1.7 | 22/160 | 13.8 |
Andersen et al, 199019 | 0/411 | 0 | 6/469 | 1.3 |
TOTALS | 221/2,000 | 11 | 105/927 | 11.3 |
SQUAMOUS MICROINVASION | ||||
Gurgel et al, 199727 | 6/74 | 8.1 | 45/76 | 59.2 |
Roman et al, 199722 | 1/30 | 3.3 | 7/50 | 14 |
TOTALS | 7/104 | 6.7 | 52/126 | 41.3 |
Follow-up of squamous lesions
Considerable clinical uncertainty remains over the relative strengths of cytologic, colposcopic, and histologic evaluation for residual or recurrent disease following excisional biopsy. Conservative management includes Papanicolaou smears alone or in combination with ECC and/or colposcopy.
Negative margins. If margins are negative, the success rate of excisional biopsy is high (90%-100%), and careful observation is the preferred follow-up. Repeat cytologic testing will identify the majority of patients with residual high-grade disease. A prospective randomized trial of cytologic surveillance showed that the detection rate was only 1.9% higher for histology.19 Although 1 report suggests that colposcopy can expedite the diagnosis of recurrent dysplasia, it is unclear from this report whether colposcopy identified significant high-grade dysplasia that cytology missed.20
Positive margins. In most series involving CIN with positive margins, treatment success rates do not differ significantly between patients who undergo repeat surgical procedures and those who have close follow-up. However, endocervical margin involvement appears to carry a higher treatment failure rate than ectocervical margin involvement. Data are conflicting on the proper method of conservative follow-up. Some authors propose only frequent cytologic testing, while others recommend that colposcopy be performed.19-21
For patients with positive margins, I perform both cytology and colposcopy in 4 to 6 months. If an endocervical margin was positive, I also perform an ECC. If this evaluation is negative, I repeat cytologic testing every 6 months until 3 consecutive Pap smears are normal and satisfactory. In cases of recurrent high-grade dysplasia with positive margins, hysterectomy may be indicated, depending on the patient’s age and desire for continued fertility.14,21
Squamous microinvasion
There is a significant risk (50%-80%) of residual disease or true invasion when margins or an ECC are positive and microinvasion is present.2,5-7 In these cases, a repeat excisional biopsy should be performed to determine the true extent of disease prior to deciding on definitive therapy.22 As previously mentioned, CKC is preferred to limit artifact that could obscure interpretation. If the patient has completed her childbearing, hysterectomy remains the standard treatment for microinvasive squamous cell carcinoma. When the woman wishes to preserve fertility, conservative follow-up appears to be safe if the final pathologic specimen has negative margins. A follow-up protocol including cytologic, colposcopic, and ECC monitoring in the first post-conization visit is recommended.2,6
Glandular lesions
AIS with involved margins requires further surgery due to the possibility of residual AIS or invasion (TABLES 2 and 3).2,5-7 In these cases, CKC is preferable to LEEP.3,5-7 Hysterectomy remains the standard therapy for AIS. Conservative management is an option if fertility is desired and margin status is negative. Patients should be informed that persistent disease or recurrence is possible and that there is a risk of invasive disease.15
Counseling, thorough documentation, and second surgical and pathologic opinions may be helpful in conservative management. Colposcopy, ECC, and cytology are indicated at the first follow-up visit, with cytology repeated every 6 months until 4 consecutive Paps are normal. More frequent colposcopy and liberal use of ECC also may be considered.
TABLE 2
Residual disease and margin status: adenocarcinoma in situ
AUTHOR | PROPORTION WITH RESIDUAL DISEASE | |||
---|---|---|---|---|
NEGATIVE MARGINS | POSITIVE MARGINS | |||
NUMBER | % | NUMBER | % | |
Azodi et al, 199928 | 5/16 | 31.3 | 9/16 | 56.3 |
Goldstein et al, 199828 | 13/43 | 30.2 | 8/18 | 44.4 |
Denehy et al, 19976 | 2/7 | 28.6 | 7/10 | 70 |
Widrich et al, 19965 | 0/3 | 0 | 9/14 | 64.3 |
Wolf et al, 199629 | 7/21 | 33.3 | 10/19 | 52.6 |
TOTAL | 27/90 | 30 | 43/77 | 55.8 |
TABLE 3
Follow-up recommendations
Pathology | Margin status | Recommendation |
---|---|---|
High-grade squamous lesion | Negative |
|
Positive, endocervical |
| |
Positive, ectocervical |
| |
Squamous microinvasion | Negative, fertility desired |
|
Negative, no desire for fertility | Hysterectomy | |
Positive | CKC | |
Adenocarcinoma in situ | Negative, fertility desired |
|
Negative, no desire for fertility | Hysterectomy | |
Positive | CKC | |
CKC = cold-knife conization; ECC = endocervical curettage |
When further excision is necessary
As noted earlier, repeat excision is necessary in cases of squamous microinvasion or AIS with positive margins. CKC is generally preferred to allow for optimal pathologic interpretation. For squamous intraepithelial lesions, excisional biopsy with close follow-up has a significant cure rate, and hysterectomy usually is not indicated. However, hysterectomy still should be considered part of the treatment continuum for CIN, particularly for patients who have completed childbearing.
Conclusion
Although the risk of recurrence is correlated with a patient’s margin status in cases of squamous dysplasia, conservative follow-up is possible and has a high success rate. Cytology is sufficient surveillance for cases involving negative margins. When margins are positive, colposcopy and ECC also may be useful. Microinvasive lesions with positive margins require further surgical evaluation to determine treatment. For glandular lesions, CKC is preferred for both diagnosis and treatment.
Dr. Dunton reports no affiliation or financial arrangement with any of the companies that manufacture drugs or devices in any of the product classes mentioned in this article.
- In most cases, loop electrosurgical excision procedure (LEEP) and cold-knife conization (CKC) result in equivalent success rates and margin status.
- CKC is preferred in cases of adenocarcinoma in situ or squamous microinvasion.
- Conservative follow-up is generally possible in adenocarcinoma in situ and squamous microinvasion when margins are negative.
- Colposcopy, endocervical curettage, and biopsies should be part of the follow-up strategy for patients with positive margins.
When cervical intraepithelial neoplasia (CIN) requires treatment, loop electrosurgical excision procedure (LEEP) is the most frequently used modality, although cold-knife conization (CKC) of the cervical transformation zone still is preferred in select cases. Since excisional techniques are used with CKC, margin status is known and clinical decisions may be based on this information.
This article reviews current indications for excisional biopsy and presents evidence to direct management and follow-up of patients with positive and negative margins.
Selecting a technique
Several large randomized and prospective studies have demonstrated that LEEP is similar in efficacy to CKC and may even remove less of the normal cervical stroma.1-3 In general, LEEP is used to excise high-grade and recurrent squamous dysplasia, as it is similar to CKC in its rates of incomplete excision and residual disease.1,4 However, when adenocarcinoma in situ (AIS) is present, CKC is preferred for diagnosis and treatment, since it results in a lower incidence of involved margins and a lower recurrence rate.3,5-7
CKC also is preferred when histologic confirmation of the margin status is crucial, such as when invasion with squamous lesions is suspected. This is because thermal artifacts that may result from LEEP will interfere with interpretation, further complicating treatment planning.1,4,8,9 In cases of microinvasion, the ability to confirm margins makes conservative treatment possible; if the depth of invasion cannot be determined from the specimen, radical surgery may be necessary.
In the hands of an experienced clinician, however, thermal artifact from the LEEP technique generally is not a significant problem. Series reporting high rates of uninterpretable margins have been attributed to operator inexperience.10 In general, thermal artifact is reduced by limiting the number of sections taken. In ideal cases, only a single-piece specimen is obtained, similar to that achieved using CKC.8,10,11 Newer loops, such as the cone biopsy excision loop, may decrease the number of sections and further improve margin interpretation.8
I use CKC in cases of suspected squamous invasion and in the evaluation of glandular lesions, but feel that in other cases LEEP is efficacious and quicker.
Identifying residual disease
When both the endocervical margin and endocervical curettage (ECC) are positive for squamous dysplasia at the time of excision, there is an increased risk of residual disease (TABLE 1).12-14 However, it is not clear whether ECC alone is an independent predictor of residual disease. Although 1 study suggests an increased risk of invasive cancer in women over 50 years of age with a positive ECC at the time of conization, other series have failed to demonstrate a difference in treatment failure rates based on ECC.15-17 Thus, the utility of ECC in directing further therapy at the time of excisional biopsy is unclear. I generally do not perform an ECC with LEEP for squamous dysplasia.
In AIS, a positive ECC is a strong predictor of residual disease, while a negative ECC is of limited significance.18 I am more likely to perform an ECC with glandular lesions. If it is negative, close follow-up still is indicated. If it is positive, repeat excision may be necessary.
TABLE 1
Residual disease and margin status: squamous dysplasia
AUTHOR | PROPORTION WITH RESIDUAL DISEASE | |||
---|---|---|---|---|
NEGATIVE MARGINS | POSITIVE MARGINS | |||
NUMBER | % | NUMBER | % | |
SQUAMOUS LESIONS | ||||
Bertelsen et al, 199923 | 44/485 | 9 | 29/76 | 38.2 |
Moore et al, 199524 | 170/523 | 32.5 | 37/91 | 40.7 |
Lopes et al, 199325 | 0/176 | 0 | 11/131 | 8.4 |
Murdoch et al, 199226 | 7/405 | 1.7 | 22/160 | 13.8 |
Andersen et al, 199019 | 0/411 | 0 | 6/469 | 1.3 |
TOTALS | 221/2,000 | 11 | 105/927 | 11.3 |
SQUAMOUS MICROINVASION | ||||
Gurgel et al, 199727 | 6/74 | 8.1 | 45/76 | 59.2 |
Roman et al, 199722 | 1/30 | 3.3 | 7/50 | 14 |
TOTALS | 7/104 | 6.7 | 52/126 | 41.3 |
Follow-up of squamous lesions
Considerable clinical uncertainty remains over the relative strengths of cytologic, colposcopic, and histologic evaluation for residual or recurrent disease following excisional biopsy. Conservative management includes Papanicolaou smears alone or in combination with ECC and/or colposcopy.
Negative margins. If margins are negative, the success rate of excisional biopsy is high (90%-100%), and careful observation is the preferred follow-up. Repeat cytologic testing will identify the majority of patients with residual high-grade disease. A prospective randomized trial of cytologic surveillance showed that the detection rate was only 1.9% higher for histology.19 Although 1 report suggests that colposcopy can expedite the diagnosis of recurrent dysplasia, it is unclear from this report whether colposcopy identified significant high-grade dysplasia that cytology missed.20
Positive margins. In most series involving CIN with positive margins, treatment success rates do not differ significantly between patients who undergo repeat surgical procedures and those who have close follow-up. However, endocervical margin involvement appears to carry a higher treatment failure rate than ectocervical margin involvement. Data are conflicting on the proper method of conservative follow-up. Some authors propose only frequent cytologic testing, while others recommend that colposcopy be performed.19-21
For patients with positive margins, I perform both cytology and colposcopy in 4 to 6 months. If an endocervical margin was positive, I also perform an ECC. If this evaluation is negative, I repeat cytologic testing every 6 months until 3 consecutive Pap smears are normal and satisfactory. In cases of recurrent high-grade dysplasia with positive margins, hysterectomy may be indicated, depending on the patient’s age and desire for continued fertility.14,21
Squamous microinvasion
There is a significant risk (50%-80%) of residual disease or true invasion when margins or an ECC are positive and microinvasion is present.2,5-7 In these cases, a repeat excisional biopsy should be performed to determine the true extent of disease prior to deciding on definitive therapy.22 As previously mentioned, CKC is preferred to limit artifact that could obscure interpretation. If the patient has completed her childbearing, hysterectomy remains the standard treatment for microinvasive squamous cell carcinoma. When the woman wishes to preserve fertility, conservative follow-up appears to be safe if the final pathologic specimen has negative margins. A follow-up protocol including cytologic, colposcopic, and ECC monitoring in the first post-conization visit is recommended.2,6
Glandular lesions
AIS with involved margins requires further surgery due to the possibility of residual AIS or invasion (TABLES 2 and 3).2,5-7 In these cases, CKC is preferable to LEEP.3,5-7 Hysterectomy remains the standard therapy for AIS. Conservative management is an option if fertility is desired and margin status is negative. Patients should be informed that persistent disease or recurrence is possible and that there is a risk of invasive disease.15
Counseling, thorough documentation, and second surgical and pathologic opinions may be helpful in conservative management. Colposcopy, ECC, and cytology are indicated at the first follow-up visit, with cytology repeated every 6 months until 4 consecutive Paps are normal. More frequent colposcopy and liberal use of ECC also may be considered.
TABLE 2
Residual disease and margin status: adenocarcinoma in situ
AUTHOR | PROPORTION WITH RESIDUAL DISEASE | |||
---|---|---|---|---|
NEGATIVE MARGINS | POSITIVE MARGINS | |||
NUMBER | % | NUMBER | % | |
Azodi et al, 199928 | 5/16 | 31.3 | 9/16 | 56.3 |
Goldstein et al, 199828 | 13/43 | 30.2 | 8/18 | 44.4 |
Denehy et al, 19976 | 2/7 | 28.6 | 7/10 | 70 |
Widrich et al, 19965 | 0/3 | 0 | 9/14 | 64.3 |
Wolf et al, 199629 | 7/21 | 33.3 | 10/19 | 52.6 |
TOTAL | 27/90 | 30 | 43/77 | 55.8 |
TABLE 3
Follow-up recommendations
Pathology | Margin status | Recommendation |
---|---|---|
High-grade squamous lesion | Negative |
|
Positive, endocervical |
| |
Positive, ectocervical |
| |
Squamous microinvasion | Negative, fertility desired |
|
Negative, no desire for fertility | Hysterectomy | |
Positive | CKC | |
Adenocarcinoma in situ | Negative, fertility desired |
|
Negative, no desire for fertility | Hysterectomy | |
Positive | CKC | |
CKC = cold-knife conization; ECC = endocervical curettage |
When further excision is necessary
As noted earlier, repeat excision is necessary in cases of squamous microinvasion or AIS with positive margins. CKC is generally preferred to allow for optimal pathologic interpretation. For squamous intraepithelial lesions, excisional biopsy with close follow-up has a significant cure rate, and hysterectomy usually is not indicated. However, hysterectomy still should be considered part of the treatment continuum for CIN, particularly for patients who have completed childbearing.
Conclusion
Although the risk of recurrence is correlated with a patient’s margin status in cases of squamous dysplasia, conservative follow-up is possible and has a high success rate. Cytology is sufficient surveillance for cases involving negative margins. When margins are positive, colposcopy and ECC also may be useful. Microinvasive lesions with positive margins require further surgical evaluation to determine treatment. For glandular lesions, CKC is preferred for both diagnosis and treatment.
Dr. Dunton reports no affiliation or financial arrangement with any of the companies that manufacture drugs or devices in any of the product classes mentioned in this article.
1. Mathevet P, Dargent D, Roy M, Beau G. A randomized prospective study comparing three techniques of conization: cold knife, laser, and LEEP. Gynecol Oncol. 1994;54(2):175-179.
2. Duggan BD, Felix JC, Muderspach LI, et al. Cold-knife conization versus conization by the loop electrosurgical excision procedure: a randomized, prospective study. Am J Obstet Gynecol. 1999;180:276-282.
3. Girardi F, Heydarfadi M, Koroschetz F, et al. Cold-knife conization versus loop excision: histopathologic and clinical results of a randomized trial. Gynecol Oncol. 1994;55:368-370.
4. Gold M, Dunton CJ, Murray J, et al. Loop electrocautery excisional procedure: therapeutic effectiveness as an ablation and a conization equivalent. Gynecol Oncol. 1996;61:241-244.
5. Widrich T, Kennedy AW, Myers TM, et al. Adenocarcinoma in situ of the uterine cervix: management and outcome. Gynecol Oncol. 1996;61:304-308.
6. Denehy TR, Gregori CA, Breen JL. Endocervical curettage, cone margins, and residual adenocarcinoma in situ of the cervix. Obstet Gynecol. 1997;90:1-6.
7. Muntz HG, Bell DA, Lage JM, et al. Adenocarcinoma in situ of the uterine cervix. Obstet Gynecol. 1992;80:935-939.
8. Naumann RW, Bell MC, Alvarez RD, et al. LLETZ is an acceptable alternative to diagnostic cold-knife conization. Gynecol Oncol. 1994;55:224-228.
9. Eddy GL, Spiegel GW, Creasman WT. Adverse effect of electrosurgical loop excision on assignment of FIGO stage in cervical cancer: report of two cases. Gynecol Oncol. 1994;55:313-317.
10. Montz FJ, Holschneider CH, Thompson LDR. Large-loop excision of the transformation zone: effect on the pathologic interpretation of resection margins. Obstet Gynecol. 1993;81:976-982.
11. Gardeil F, Barry-Walsh C, Prendiville W, et al. Persistent intraepithelial neoplasia after excision for cervical intraepithelial neoplasia grade III. Obstet Gynecol. 1987;89:419-422.
12. Felix JC, Muderspach LI, Duggan BD, Roman LD. The significance of positive margins in loop electrosurgical cone biopsies. Obstet Gynecol. 1994;84:996-1000.
13. Kobak WH, Roman LD, Felix JC, et al. The role of endocervical curettage at cervical conization for high-grade dysplasia. Obstet Gynecol. 1995;85:197-201.
14. Husseinzadeh N, Shbara I, Wessler T. Predictive value of cone margins and post-cone endocervical curettage with residual disease in subsequent hysterectomy. Gynecol Oncol. 1989;33:198-200.
15. Poyner EA, Barakat RR, Hoskins WJ. Management and follow-up of patients with adenocarcinoma in situ of the uterine cervix. Gynecol Oncol. 1995;57:158-164.
16. Frauchiger WL, De Frias DVS, Cajulis RS, Yu GH. The immediate postconization endocervical smear: evaluation of its utility in the detection of residual dysplasia. Acta Cytol. 1998;42:1139-1143.
17. Wright TC, Gagnon S, Richart RM, Ferenczy A. Treatment of cervical intraepithelial neoplasia using the loop electrosurgical excision procedure. Obstet Gynecol. 1992;79:173-178.
18. Goldstein NS, Mani A. The status and distance of cone biopsy margins as a predictor of excision adequacy for endocervical adenocarcinoma in situ. Am J Clin Pathol. 1998;109:727-732.
19. Andersen ES, Nielsen K, Larsen G. Laser conization: follow-up in patients with cervical intraepithelial neoplasia in the cone margin. Gynecol Oncol. 1990;39:328-331.
20. Paraskevaidis E, Jandial L, Mann EMF, Fisher PM. Pattern of treatment failure following laser for cervical intraepithelial neoplasia: implications for follow-up protocol. Obstet Gynecol. 1991;78:80-83.
21. Lapaquette TK, Dinh TV, Hannigan EV, et al. Management of patients with positive margins after cervical conization. Obstet Gynecol. 1993;82:440-443.
22. Roman LD, Felix JC, Muderspach LI, et al. Risk of residual invasive disease in women with microinvasive squamous cancer in a conization specimen. Obstet Gynecol. 1997;90:759-764.
23. Bertelsen B, Tande T, Sandvei, Hartveit F. Laser conization of cervical intraepithelial neoplasia grade 3. Acta Obstet Gynecol Scand. 1999;78:54-59.
24. Moore BC, Higgins RV, Laurent SL, et al. Predictive factors from cold knife conization for residual cervical intraepithelial neoplasia in subsequent hysterectomy. Am J Obstet Gynecol. 1995;173:361-368.
25. Lopes A, Morgan P, Murdoch J, et al. The case for conservative management of “incomplete excision” of CIN after laser conization. Gynecol Oncol. 1993;49:247-249.
26. Murdoch JB, Morgan PR, Lopes A, Monaghan JM. Histological incomplete excision of CIN after large loop excision of the transformation zone (LLETZ) merits careful follow up, not retreatment. Br J Obstet Gynaecol. 1992;99:990-993.
27. Gurgel MSC, Bedone AJ, Andrade LA, et al. Microinvasive carcinoma of the uterine cervix: histological findings on cone specimens related to residual neoplasia on hysterectomy. Gynecol Oncol. 1997;65:437-440.
28. Azodi M, Chambers SK, Rutherford TJ, et al. Adenocarcinoma in situ of the cervix: management and outcome. Gynecol Oncol. 1999;73:348-353.
29. Wolf JK, Levenback C, Malpica A, et al. Adenocarcinoma in situ of the cervix: significance of cone biopsy margins. Obstet Gynecol. 1996;88:82-86.
1. Mathevet P, Dargent D, Roy M, Beau G. A randomized prospective study comparing three techniques of conization: cold knife, laser, and LEEP. Gynecol Oncol. 1994;54(2):175-179.
2. Duggan BD, Felix JC, Muderspach LI, et al. Cold-knife conization versus conization by the loop electrosurgical excision procedure: a randomized, prospective study. Am J Obstet Gynecol. 1999;180:276-282.
3. Girardi F, Heydarfadi M, Koroschetz F, et al. Cold-knife conization versus loop excision: histopathologic and clinical results of a randomized trial. Gynecol Oncol. 1994;55:368-370.
4. Gold M, Dunton CJ, Murray J, et al. Loop electrocautery excisional procedure: therapeutic effectiveness as an ablation and a conization equivalent. Gynecol Oncol. 1996;61:241-244.
5. Widrich T, Kennedy AW, Myers TM, et al. Adenocarcinoma in situ of the uterine cervix: management and outcome. Gynecol Oncol. 1996;61:304-308.
6. Denehy TR, Gregori CA, Breen JL. Endocervical curettage, cone margins, and residual adenocarcinoma in situ of the cervix. Obstet Gynecol. 1997;90:1-6.
7. Muntz HG, Bell DA, Lage JM, et al. Adenocarcinoma in situ of the uterine cervix. Obstet Gynecol. 1992;80:935-939.
8. Naumann RW, Bell MC, Alvarez RD, et al. LLETZ is an acceptable alternative to diagnostic cold-knife conization. Gynecol Oncol. 1994;55:224-228.
9. Eddy GL, Spiegel GW, Creasman WT. Adverse effect of electrosurgical loop excision on assignment of FIGO stage in cervical cancer: report of two cases. Gynecol Oncol. 1994;55:313-317.
10. Montz FJ, Holschneider CH, Thompson LDR. Large-loop excision of the transformation zone: effect on the pathologic interpretation of resection margins. Obstet Gynecol. 1993;81:976-982.
11. Gardeil F, Barry-Walsh C, Prendiville W, et al. Persistent intraepithelial neoplasia after excision for cervical intraepithelial neoplasia grade III. Obstet Gynecol. 1987;89:419-422.
12. Felix JC, Muderspach LI, Duggan BD, Roman LD. The significance of positive margins in loop electrosurgical cone biopsies. Obstet Gynecol. 1994;84:996-1000.
13. Kobak WH, Roman LD, Felix JC, et al. The role of endocervical curettage at cervical conization for high-grade dysplasia. Obstet Gynecol. 1995;85:197-201.
14. Husseinzadeh N, Shbara I, Wessler T. Predictive value of cone margins and post-cone endocervical curettage with residual disease in subsequent hysterectomy. Gynecol Oncol. 1989;33:198-200.
15. Poyner EA, Barakat RR, Hoskins WJ. Management and follow-up of patients with adenocarcinoma in situ of the uterine cervix. Gynecol Oncol. 1995;57:158-164.
16. Frauchiger WL, De Frias DVS, Cajulis RS, Yu GH. The immediate postconization endocervical smear: evaluation of its utility in the detection of residual dysplasia. Acta Cytol. 1998;42:1139-1143.
17. Wright TC, Gagnon S, Richart RM, Ferenczy A. Treatment of cervical intraepithelial neoplasia using the loop electrosurgical excision procedure. Obstet Gynecol. 1992;79:173-178.
18. Goldstein NS, Mani A. The status and distance of cone biopsy margins as a predictor of excision adequacy for endocervical adenocarcinoma in situ. Am J Clin Pathol. 1998;109:727-732.
19. Andersen ES, Nielsen K, Larsen G. Laser conization: follow-up in patients with cervical intraepithelial neoplasia in the cone margin. Gynecol Oncol. 1990;39:328-331.
20. Paraskevaidis E, Jandial L, Mann EMF, Fisher PM. Pattern of treatment failure following laser for cervical intraepithelial neoplasia: implications for follow-up protocol. Obstet Gynecol. 1991;78:80-83.
21. Lapaquette TK, Dinh TV, Hannigan EV, et al. Management of patients with positive margins after cervical conization. Obstet Gynecol. 1993;82:440-443.
22. Roman LD, Felix JC, Muderspach LI, et al. Risk of residual invasive disease in women with microinvasive squamous cancer in a conization specimen. Obstet Gynecol. 1997;90:759-764.
23. Bertelsen B, Tande T, Sandvei, Hartveit F. Laser conization of cervical intraepithelial neoplasia grade 3. Acta Obstet Gynecol Scand. 1999;78:54-59.
24. Moore BC, Higgins RV, Laurent SL, et al. Predictive factors from cold knife conization for residual cervical intraepithelial neoplasia in subsequent hysterectomy. Am J Obstet Gynecol. 1995;173:361-368.
25. Lopes A, Morgan P, Murdoch J, et al. The case for conservative management of “incomplete excision” of CIN after laser conization. Gynecol Oncol. 1993;49:247-249.
26. Murdoch JB, Morgan PR, Lopes A, Monaghan JM. Histological incomplete excision of CIN after large loop excision of the transformation zone (LLETZ) merits careful follow up, not retreatment. Br J Obstet Gynaecol. 1992;99:990-993.
27. Gurgel MSC, Bedone AJ, Andrade LA, et al. Microinvasive carcinoma of the uterine cervix: histological findings on cone specimens related to residual neoplasia on hysterectomy. Gynecol Oncol. 1997;65:437-440.
28. Azodi M, Chambers SK, Rutherford TJ, et al. Adenocarcinoma in situ of the cervix: management and outcome. Gynecol Oncol. 1999;73:348-353.
29. Wolf JK, Levenback C, Malpica A, et al. Adenocarcinoma in situ of the cervix: significance of cone biopsy margins. Obstet Gynecol. 1996;88:82-86.
Cryotherapy: Evidence-Based Interventions and Informed Consent
Cryotherapy is an effective, affordable, and safe treatment for cervical dysplasia. Despite newer technologies such as laser and loop excision, cryotherapy continues to be commonly used when the colposcopy is satisfactory, the lesions are 2 or less quadrants of the cervix, no endocervical disease is present, and there is no suspicion of invasive cancer.
In this issue of the Journal, Harper and colleagues1,2 have presented 2 studies of the natural history of side effects of cervical cryosurgery. They have documented several important points concerning the period immediately post-treatment that have clinical implications.Hydrorrhea is an expected finding after cryotherapy. These 2 papers document the long duration of hydrorrhea (mean=11.4 days, range=1 to 57 days) and its significant discomfort to patients. More than half of the women felt this side effect was bothersome, and 25% of the group characterized it as very or extremely so. Two thirds of the patients required medication in the postoperative period. The authors have also identified subgroups (obese, multiparous, and older patients) that are more likely to suffer from these complications.
These findings have clear-cut implications concerning informed consent before cryotherapy. Patients should be informed of the expected duration of the hydrorrhea and the postoperative analgesia that may be required. Obese, multiparous, and older women should be told that on average their postoperative course tends to be more severe. Some patients may request other treatment options. Those who choose cryotherapy as a treatment option may be reassured that their healing in the postoperative period is normal.
Future Research
The work by Harper and coworkers shows that quality of life is affected by cryosurgery treatment. Future research should be done to determine how diminished the quality-of-life utilities are. The decision to use cryosurgery versus an excisional method, such as the loop electrosurgical excision procedure, most likely hinges on the experience of the treatment procedure rather than the effectiveness of the procedure. Before any cost-effectiveness analysis of cervical dysplasia treatments can be completed, the quality-of-life measures for all treatment procedures must be delineated. Only then can the quality-adjusted effectiveness of the treatment procedures be compared. Implicit in the comparison of cryosurgery to loop excision is the assumption that both treatments are equally effective for the particular cervical lesion.
Cryosurgery is often used for treatment of cervical intraepithelial neoplasia grade 1 (CIN 1) lesions. We recognize that CIN 1 lesions are a manifestation of human papillomavirus infection and will regress to normal cervical tissue without intervention approximately 60% to 80% of the time. Using a destructive method for CIN 1 lesions that has significant sequelae should be studied in a cost-effective manner, taking into account the expressed quality of life. The cost-effectiveness analysis may show us that it is rational to conservatively manage women with CIN 1 for a year then treat with cryosurgery if the lesion is still present, or it may show that immediate treatment is most cost-effective. This important work is yet to be done.
In addition, it is anticipated that the compliance rate with future routine screening practices could be affected by the cervical treatment procedure chosen. If women do not return in a timely manner for rescreening after treatment because of the bad healing experience, the effectiveness of our cervical cancer screening strategy could be diminished.
I hope the authors will continue their study and compare the cryosurgical healing with that of loop excision. Reported complications are low for loop excision, but there have been no carefully done studies of patient-based experiences with it. It is important to establish the complete healing sequelae after loop excision and to measure patients’ disutilities in a similar fashion to the studies by Harper and colleagues.
The most important clinical observations from these 2 studies are the side effects of pain and cramping and protracted hydrorrhea. It is likely that these may influence future screening and treatment. If cryosurgery intervention for CIN 1 and its side effects limit future screening and treatment, more harm than good may be done by therapy. Clinicians need to consider the information Harper and coworkers have presented when choosing to recommend therapy.
1. DM, Mayeaux EJ, Daaleman TP, Woodward LD, Ferris DG, Johnson CA. The natural history of cervical cryosurgical healing: the minimal effect of debridement of the cervical eschar. J Fam Pract 2000;49:764-700.
2. DM, Mayeaux EJ, Daaleman TP, Johnson CA. Healing experiences after cervical cryosurgery: implications for informed consent. J Fam Pract 2000;49:701-706.
Cryotherapy is an effective, affordable, and safe treatment for cervical dysplasia. Despite newer technologies such as laser and loop excision, cryotherapy continues to be commonly used when the colposcopy is satisfactory, the lesions are 2 or less quadrants of the cervix, no endocervical disease is present, and there is no suspicion of invasive cancer.
In this issue of the Journal, Harper and colleagues1,2 have presented 2 studies of the natural history of side effects of cervical cryosurgery. They have documented several important points concerning the period immediately post-treatment that have clinical implications.Hydrorrhea is an expected finding after cryotherapy. These 2 papers document the long duration of hydrorrhea (mean=11.4 days, range=1 to 57 days) and its significant discomfort to patients. More than half of the women felt this side effect was bothersome, and 25% of the group characterized it as very or extremely so. Two thirds of the patients required medication in the postoperative period. The authors have also identified subgroups (obese, multiparous, and older patients) that are more likely to suffer from these complications.
These findings have clear-cut implications concerning informed consent before cryotherapy. Patients should be informed of the expected duration of the hydrorrhea and the postoperative analgesia that may be required. Obese, multiparous, and older women should be told that on average their postoperative course tends to be more severe. Some patients may request other treatment options. Those who choose cryotherapy as a treatment option may be reassured that their healing in the postoperative period is normal.
Future Research
The work by Harper and coworkers shows that quality of life is affected by cryosurgery treatment. Future research should be done to determine how diminished the quality-of-life utilities are. The decision to use cryosurgery versus an excisional method, such as the loop electrosurgical excision procedure, most likely hinges on the experience of the treatment procedure rather than the effectiveness of the procedure. Before any cost-effectiveness analysis of cervical dysplasia treatments can be completed, the quality-of-life measures for all treatment procedures must be delineated. Only then can the quality-adjusted effectiveness of the treatment procedures be compared. Implicit in the comparison of cryosurgery to loop excision is the assumption that both treatments are equally effective for the particular cervical lesion.
Cryosurgery is often used for treatment of cervical intraepithelial neoplasia grade 1 (CIN 1) lesions. We recognize that CIN 1 lesions are a manifestation of human papillomavirus infection and will regress to normal cervical tissue without intervention approximately 60% to 80% of the time. Using a destructive method for CIN 1 lesions that has significant sequelae should be studied in a cost-effective manner, taking into account the expressed quality of life. The cost-effectiveness analysis may show us that it is rational to conservatively manage women with CIN 1 for a year then treat with cryosurgery if the lesion is still present, or it may show that immediate treatment is most cost-effective. This important work is yet to be done.
In addition, it is anticipated that the compliance rate with future routine screening practices could be affected by the cervical treatment procedure chosen. If women do not return in a timely manner for rescreening after treatment because of the bad healing experience, the effectiveness of our cervical cancer screening strategy could be diminished.
I hope the authors will continue their study and compare the cryosurgical healing with that of loop excision. Reported complications are low for loop excision, but there have been no carefully done studies of patient-based experiences with it. It is important to establish the complete healing sequelae after loop excision and to measure patients’ disutilities in a similar fashion to the studies by Harper and colleagues.
The most important clinical observations from these 2 studies are the side effects of pain and cramping and protracted hydrorrhea. It is likely that these may influence future screening and treatment. If cryosurgery intervention for CIN 1 and its side effects limit future screening and treatment, more harm than good may be done by therapy. Clinicians need to consider the information Harper and coworkers have presented when choosing to recommend therapy.
Cryotherapy is an effective, affordable, and safe treatment for cervical dysplasia. Despite newer technologies such as laser and loop excision, cryotherapy continues to be commonly used when the colposcopy is satisfactory, the lesions are 2 or less quadrants of the cervix, no endocervical disease is present, and there is no suspicion of invasive cancer.
In this issue of the Journal, Harper and colleagues1,2 have presented 2 studies of the natural history of side effects of cervical cryosurgery. They have documented several important points concerning the period immediately post-treatment that have clinical implications.Hydrorrhea is an expected finding after cryotherapy. These 2 papers document the long duration of hydrorrhea (mean=11.4 days, range=1 to 57 days) and its significant discomfort to patients. More than half of the women felt this side effect was bothersome, and 25% of the group characterized it as very or extremely so. Two thirds of the patients required medication in the postoperative period. The authors have also identified subgroups (obese, multiparous, and older patients) that are more likely to suffer from these complications.
These findings have clear-cut implications concerning informed consent before cryotherapy. Patients should be informed of the expected duration of the hydrorrhea and the postoperative analgesia that may be required. Obese, multiparous, and older women should be told that on average their postoperative course tends to be more severe. Some patients may request other treatment options. Those who choose cryotherapy as a treatment option may be reassured that their healing in the postoperative period is normal.
Future Research
The work by Harper and coworkers shows that quality of life is affected by cryosurgery treatment. Future research should be done to determine how diminished the quality-of-life utilities are. The decision to use cryosurgery versus an excisional method, such as the loop electrosurgical excision procedure, most likely hinges on the experience of the treatment procedure rather than the effectiveness of the procedure. Before any cost-effectiveness analysis of cervical dysplasia treatments can be completed, the quality-of-life measures for all treatment procedures must be delineated. Only then can the quality-adjusted effectiveness of the treatment procedures be compared. Implicit in the comparison of cryosurgery to loop excision is the assumption that both treatments are equally effective for the particular cervical lesion.
Cryosurgery is often used for treatment of cervical intraepithelial neoplasia grade 1 (CIN 1) lesions. We recognize that CIN 1 lesions are a manifestation of human papillomavirus infection and will regress to normal cervical tissue without intervention approximately 60% to 80% of the time. Using a destructive method for CIN 1 lesions that has significant sequelae should be studied in a cost-effective manner, taking into account the expressed quality of life. The cost-effectiveness analysis may show us that it is rational to conservatively manage women with CIN 1 for a year then treat with cryosurgery if the lesion is still present, or it may show that immediate treatment is most cost-effective. This important work is yet to be done.
In addition, it is anticipated that the compliance rate with future routine screening practices could be affected by the cervical treatment procedure chosen. If women do not return in a timely manner for rescreening after treatment because of the bad healing experience, the effectiveness of our cervical cancer screening strategy could be diminished.
I hope the authors will continue their study and compare the cryosurgical healing with that of loop excision. Reported complications are low for loop excision, but there have been no carefully done studies of patient-based experiences with it. It is important to establish the complete healing sequelae after loop excision and to measure patients’ disutilities in a similar fashion to the studies by Harper and colleagues.
The most important clinical observations from these 2 studies are the side effects of pain and cramping and protracted hydrorrhea. It is likely that these may influence future screening and treatment. If cryosurgery intervention for CIN 1 and its side effects limit future screening and treatment, more harm than good may be done by therapy. Clinicians need to consider the information Harper and coworkers have presented when choosing to recommend therapy.
1. DM, Mayeaux EJ, Daaleman TP, Woodward LD, Ferris DG, Johnson CA. The natural history of cervical cryosurgical healing: the minimal effect of debridement of the cervical eschar. J Fam Pract 2000;49:764-700.
2. DM, Mayeaux EJ, Daaleman TP, Johnson CA. Healing experiences after cervical cryosurgery: implications for informed consent. J Fam Pract 2000;49:701-706.
1. DM, Mayeaux EJ, Daaleman TP, Woodward LD, Ferris DG, Johnson CA. The natural history of cervical cryosurgical healing: the minimal effect of debridement of the cervical eschar. J Fam Pract 2000;49:764-700.
2. DM, Mayeaux EJ, Daaleman TP, Johnson CA. Healing experiences after cervical cryosurgery: implications for informed consent. J Fam Pract 2000;49:701-706.