Secondary Logo

Journal Logo

2001 Consensus Guidelines for the Management of Women with Cervical Cytological Abnormalities

Wright, Thomas C. Jr. MD1; Cox, J. Thomas MD2; Massad, L. Stewart MD3; Twiggs, Leo B. MD4; Wilkinson, Edward J. MD5 2001 ASCCP-sponsored Consensus Conference

Journal of Lower Genital Tract Disease: April 2002 - Volume 6 - Issue 2 - p 127-143
2001 CONSENSUS GUIDELINES
Free

1 Department of Pathology, College of Physicians and Surgeons, Columbia University, New York, NY; 2 Student Health Services, University of California, Santa Barbara, Santa Barbara, CA, and American Social Health Association, Durham, NC; 3 Department of Obstetrics and Gynecology, Cook County Hospital, Chicago, IL; 4 Institute of Women's Health, University of Miami, Miami, FL; and 5 Department of Pathology, University of Florida College of Medicine, Gainesville, FL

This article was adapted from the original article that appeared in JAMA (2002;287:2120–2129) and is available at http://www.jama.com. The guidelines should be considered a guide not a standard of care. All rights reserved.

Reprint requests to: Thomas C. Wright, Jr., MD, Department of Pathology, College of Physicians and Surgeons, Columbia University, Room 16–404 P&S Building, 630 W. 168th St., New York, NY 10032. E-mail: tcw1@columbia.edu

Each year in the United States, approximately 3.3 million Pap tests are interpreted as having some degree of cytological abnormality [1]. Identifying which of these women are at risk for having a clinically significant cervical abnormality, performing a diagnostic evaluation, and treating clinically significant abnormalities once identified presents a serious clinical and public health problem that has been estimated to cost billions of dollars [2]. This challenge is amplified by the fact that Pap tests are obtained in a variety of clinical settings, including school-based health clinics, sexually transmitted disease clinics, family planning clinics and private physician offices, as well as hospitals and emergency rooms. A spectrum of health care providers is responsible for cervical cancer screening in these various settings, and many of these clinicians have little expertise in managing cervical cytological abnormalities. Because of the magnitude of the clinical problem, there is a clear need for comprehensive, evidence-based guidelines for the management of cervical cytological abnormalities and cervical cancer precursors.

There are a number of other reasons why new management guidelines are needed. In May 2001, the National Cancer Institute held a consensus workshop to revise the cervical cytological classification system used in the United States, which is now referred to as the 2001 Bethesda System. The 2001 Bethesda System changes the criteria used by cytologists to render an interpretation of atypical squamous cells (ASC), provides new subcategories of ASC, and changes the subcategories of atypical glandular cells (AGC) [3]. The ASC category is the most common cervical cytological abnormality in the United States, and management guidelines need to be revised to incorporate these changes in terminology. Other reasons for developing new management guidelines are a better understanding of the pathogenesis and natural history of human papillomavirus (HPV) and cervical cancer precursors and the availability of data from the large National Cancer Institute's Atypical Squamous Cells of Undetermined Significance/Low-grade Squamous Intraepithelial Lesion Study (ALTS) clinical trial [3a]. This $25 million, multisite, randomized clinical trial was designed specifically to address the best management approaches for women with a cytological result of ASC and low-grade squamous intraepithelial lesions (LSIL). The results of this trial need to be incorporated into clinical care of women in the United States. It is also important to recognize that current guidelines were developed before sensitive molecular methods for detecting high-risk types of HPV and liquid-based cytology methods became widely available. There is now compelling data that combining these two new technologies provides an attractive alternative to the more traditional management approaches for certain types of cytological abnormalities [4–6]. As a result, the use of these new technologies is increasing, and clinicians need clear, unbiased guidelines delineating the strengths and weakness of different management approaches and the best use of the new technologies.

To develop comprehensive management strategies for women with cytological abnormalities and cervical cancer precursors, the American Society of Colposcopy and Cervical Pathology (ASCCP) sponsored a National Consensus Conference in Bethesda, MD, on September 6–8, 2001. This meeting had representatives from 29 national and international health organizations, professional societies, and federal agencies. Throughout the development of the guidelines, input was obtained from the professional community at large through a novel approach that incorporated Internet-based discussion groups. This report provides a summary of the key recommendations and algorithms for managing women with cytological abnormalities. A description of the evidence supporting the guidelines and the guidelines themselves have previously been published [7]. Comprehensive literature reviews of the evidence base supporting the recommendations will be published by each of the four Consensus Conference working groups [atypical squamous cells (ASC); atypical glandular cells (AGC); low-grade squamous intraepithelial lesion (LSIL); and high-grade squamous intraepithelial lesion (HSIL)] at a later date in the Journal of Lower Genital Tract Disease. In addition, separate 2001 Consensus Guidelines for the Management of Women with Cervical Histological Abnormalities will also be published at a later date.

Back to Top | Article Outline

OVERVIEW OF GUIDELINE DEVELOPMENT PROCEDURES

ASCCP began developing the 2001 Consensus Guidelines in the fall of 2000. To ensure that the guidelines reflect the needs of the diverse array of health care providers, federal agencies and national and international health organizations involved in the health care of women were invited to participate in the guideline development process. Twenty-nine different agencies and organizations agreed to formally participate, or in some instances to formally observe, the Consensus Conference and to send 2 to 4 representatives (seeAppendix 1). In total, 121 representatives attended the Consensus Conference. These included cytopathologists, cytotechnologists, epidemiologists, family physicians, gynecologists, gynecological oncologists, health policy experts, lawyers, nurse clinicians, social scientists, and pathologists. All are recognized experts in various aspects of the diagnosis and management of cervical cancer precursors.

Approximately 6 months before the conference, four working groups composed of 10 to 11 participants each began developing draft guidelines through a multistep process. First, a list of key questions that needed to be addressed by literature reviews and comment from the professional community was prepared. These questions were posted on an open Internet bulletin board (http://www.asccp.org) for public discussion. Working groups also conducted MEDLINE searches of English-language, peer-reviewed articles published between at least 1988 and 2001 to identify articles pertaining to the key questions. Abstracts of articles were reviewed by members of the working group to determine their relevancy, and the relevant articles were reviewed to determine whether they fulfilled a minimum scientific standard. Data from articles that fulfilled this standard was extracted using data extraction forms, and summary data tables were prepared for many of the specific topics. Based on the literature review, draft management guidelines were developed. In instances in which published data pertaining to a key issue was either conflicting, scant, or simply missing, information provided by participants of the Internet bulletin boards or expert opinions of members of the working group were used to help formulate the guidelines.

Draft guidelines were posted on the open Internet bulletin board for public comment and discussion. Once the discussion period was closed, the draft guidelines were revised by the working groups in light of the public comments and distributed to each of the Consensus Conference participants for review. At the conference, each participant was provided with an electronic numeric keypad that allowed “real-time” voting. Review and adoption of the guidelines took place in three stages. Initially, the draft guidelines and supporting evidence were presented by the working group to the entire Consensus Conference for discussion and voting. Any recommendation that was approved by 66% of the conference participants was accepted. Recommendations that were not approved underwent revision in open working sessions, and the revised recommendations were again discussed and voted on. If the revised recommendation was not accepted, it underwent a second round of revision and was again presented to the Consensus Conference for a third vote. All guidelines were accepted by a two-thirds majority vote.

All recommendations are graded using a grading system based on one that has been successfully used for a number of years by the Infectious Disease Society of America (IDSA) for evidence-based practice guidelines [8,9]. More than 30 practice guidelines have been produced by the IDSA using this grading system (with or without minor modifications). Recent important guidelines that have used this grading system include the 1999 Guidelines for the Prevention of Opportunistic Infections in Persons with HIV (and the as yet unreleased 2001 update), produced by a joint panel of the National Institute of Allergy and Infectious Disease, the Centers for Disease Control and Prevention, and the IDSA. The two-part grading system is also almost identical to the one utilized by the US Preventative Services Task Force in its Guide to Clinical Preventative Services. The grading system that was used for the 2001 Consensus Guidelines is a two-part grading system [10]. In this system, the letters A–E reflect the “strength of the recommendation” for or against the use of a particular option (i.e., good, moderate, or insufficient) (Table 1). Roman numerals I–III were used to indicate the “quality of evidence” supporting the recommendation (Table 1). In addition, the terms “recommended,” “preferred,” “acceptable,” and “unacceptable” were specifically defined at the Consensus Conference (Table 1). It was felt that providing an indication of the strength of the evidence supporting each guideline was particularly important in a field in which clinical opinion or small case studies are frequently all that's available to guide a recommendation. Giving the strength of the evidence for a given guideline also provides the additional benefit of highlighting areas in which research is needed. It is expected that the 2001 Consensus Guidelines will be updated on a regular basis; and it is hoped that, with each revision, the data in support of a given practice guideline will become stronger as a result of the grading system.

Table 1

Table 1

Back to Top | Article Outline

2001 CONSENSUS GUIDELINES FOR MANAGING WOMEN WITH CYTOLOGICAL ABNORMALITIES

General Comments

Although the 2001 Consensus Guidelines are “evidenced-based,” in many instances the evidence that was available to inform the development of a particular guideline was quite limited. This resulted in instances in which the guidelines had to be based on either relatively small studies or simply on expert opinion. It is also important to recognize that, although the 2001 Consensus Guidelines are designed to provide guidance to clinicians caring for women with cytological abnormalities and cervical cancer precursors in the United States, management approaches will frequently need to be individualized to take into account individual patients' clinical findings and preferences. There is a general consensus that guidelines should never be considered a substitute for clinical judgment and that it is impossible to develop guidelines comprehensive enough to apply to all clinical situations. Finally, both clinicians and patients need to realize that, although cervical cancer can often be prevented through a program of screening and treatment of cervical cancer precursor lesions, no screening or treatment modality is perfect and, unfortunately, invasive cervical cancer can develop in women who participate in such programs.

The 2001 Bethesda System for cytological classification, which uses the terms low-grade squamous intraepithelial lesion (LSIL) and high-grade squamous intraepithelial lesion (HSIL) to refer to cervical cancer precursors, is used for the guidelines. The 2001 Consensus Guidelines have utilized a two-tiered terminology for the histopathological classification that uses the terms cervical intraepithelial neoplasia–grade 1 (CIN 1) and CIN 2,3 to refer to low-grade and high-grade precursors, respectively [11]. Several terms are used throughout the guidelines, and these have been clarified in Appendix 2.

Back to Top | Article Outline

Atypical Squamous Cells

General Comments.

The 2001 Bethesda System subcategorizes ASC into two categories: atypical squamous cells of undetermined significance (ASC-US) and atypical squamous cells–cannot exclude HSIL (ASC-H) [3]. The prevalence of ASC varies considerably between laboratories and patient populations [1]. In 1997 the median ASC rate of laboratories participating in the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology (PAP) was 4.4% [1].

Several points need to be understood to interpret the consensus guidelines for the management of ASC. The first is that even with expert cytologists, the diagnosis of ASC is poorly reproducible [12–14]. For example, in the recent ALTS trial, only 55% of the cytology specimens originally diagnosed as ASC were subsequently given a diagnosis of ASC by the pathology quality control group [5]. Many of the slides initially interpreted as ASC were subsequently classified as normal. Second, a woman with a cytological diagnosis of ASC has a 5% to 17% chance of having biopsy-confirmed CIN 2,3 [5,15–17]. However, the risk that a woman with ASC has invasive cervical cancer is low (approximately 0.1%–0.2%) [18,19]. The prevalence of CIN 2,3 is considerably higher (24%–94%) among women referred for colposcopy (seeAppendix 2) for the evaluation of ASC-H compared with women referred for the evaluation of ASC-US [20–24]. Therefore, a woman with an ASC result requires some form of additional evaluation, but clinicians should attempt to minimize anxiety, cost, inconvenience, and patient discomfort during workup or follow-up.

Back to Top | Article Outline

Recommendations for Managing Women with ASC.

Management of Women with Atypical Squamous Cells—Undetermined Significance.

A program of repeat cervical cytology, or colposcopy, or DNA testing for high-risk types of HPV are all acceptable methods for managing women with ASC-US (AI). When liquid-based cytology is used, or when co-collection for HPV DNA testing can be done, “reflex” HPV DNA testing is the preferred approach (AI). *

DNA testing for high-risk types of HPV should be performed using a sensitive molecular test, and all women who are HPV DNA positive should be referred for colposcopic evaluation (AII). Women with ASC-US who are high-risk HPV DNA negative can be followed up with repeat cytology at 12 months (BII). Acceptable management options for women who are positive for high-risk types of HPV but who do not have biopsy-confirmed CIN include follow-up with repeat cytology at 6 and 12 months with referral back to colposcopy if a result of ASC-US or greater is obtained, or HPV DNA testing at 12 months with referral back to colposcopy of all HPV DNA positive women (BII) (Figure 1).

Figure 1.

Figure 1.

When a program of repeat cervical cytology is used, women with ASC-US should undergo repeat cytological testing (either conventional or liquid-based) at 4- to 6-month intervals until two consecutive “negative for intraepithelial lesion or malignancy” results are obtained (AII). Women diagnosed with ASC-US or greater cytological abnormality on the repeat tests should be referred for colposcopy (AII). After two “negative for intraepithelial lesion or malignancy” repeat cytology tests are obtained, women can be returned to routine cytological screening programs (AII).

When immediate colposcopy is used to manage women with ASC-US, women who are referred to colposcopy and not found to have CIN should be followed up with repeat cytology at 12 months (BII). Women with ASC-US who are referred for colposcopy and found to have biopsy-confirmed CIN should be managed according to the appropriate 2001 Consensus Guideline for the Management of Women with Cervical Histological Abnormalities (submitted for publication).

Because of the potential for overtreatment, diagnostic excisional procedures (seeAppendix 2) such as loop electrosurgical excision should not be routinely used to treat women with ASC in the absence of biopsy-confirmed CIN (EII).

Back to Top | Article Outline

ASC-US in Special Circumstances.

Postmenopausal Women.

Providing a course of intravaginal estrogen followed by a repeat cervical cytology obtained approximately a week after completing the regimen is an acceptable option for women with ASC-US who have clinical or cytological evidence of atrophy and no contraindications to using intravaginal estrogen (CIII). If the repeat cervical cytology is “negative for intraepithelial lesion or malignancy,” the cervical cytology should be repeated in 4 to 6 months. If both repeat cytology tests are “negative for intraepithelial lesion or malignancy,” the patient can return to routine cytological screening; but if either repeat cytology is reported as ASC-US or greater, the patient should be referred for colposcopy (AII) (Figure 2).

Figure 2.

Figure 2.

Back to Top | Article Outline
Immunosuppressed Patients.

Referral for colposcopy is recommended for all immunosuppressed patients with ASC-US (BII). This includes all HIV-infected women, irrespective of CD4 count, HIV viral load, or antiretroviral therapy.

Back to Top | Article Outline
Pregnant Patients.

It is recommended that pregnant women with ASC-US be managed in the same manner as nonpregnant women (BIII).

Back to Top | Article Outline

Management of Women with ASC-H.

The recommended management of women with ASC-H obtained using either conventional or liquid-based cervical cytology is referral for colposcopic evaluation (AII) (Figure 3).

Figure 3.

Figure 3.

When no lesion is identified after colposcopy in women with ASC-H, it is recommended that, when possible, a review of the cytology, colposcopy and histology be performed (CIII). If the review yields a revised interpretation, management should follow guidelines for the revised interpretation; if a cytological interpretation of ASC-H is upheld, either cytological follow-up at 6 and 12 months or HPV DNA testing at 12 months is acceptable (CIII). Women who are found to have ASC or greater on their repeat cervical cytology or who are subsequently high-risk HPV DNA positive should be referred for colposcopy.

Back to Top | Article Outline

Atypical Glandular Cells and Adenocarcinoma In Situ

General Comments.

Glandular cell abnormalities less severe than adenocarcinoma are classified into three categories in the 2001 Bethesda System [3]. These are atypical glandular cells (either endocervical, endometrial, or “glandular cells”) not otherwise specified (AGC NOS); atypical glandular cells (either endocervical or “glandular cells”), “favor neoplasia” (AGC–favor neoplasia); and endocervical adenocarcinoma in situ (AIS) [3]. In 1996, the median AGC rate of laboratories in the United States was 0.3% [1].

While most women with AGC do not have a significant cervical neoplasia, this category is of substantially greater risk than the category of ASC or LSIL [25]. Biopsy-confirmed CIN is found in 9%–54% of women with AGC, biopsy-confirmed AIS is identified in 0–8%, and invasive cervical cancers are identified in <1%–9% [18,25–31]. The majority of cancers in women over the age of 35 with AGC are endometrial in origin [25,32]. Subclassification of AGC into two categories termed “not otherwise specified” (NOS) and “favor neoplasia” identifies women at different risks for having high-grade neoplasia or cancer. Biopsy-confirmed invasive cancers, AIS, or CIN 2,3 have been detected in 9%–41% of women with AGC NOS compared with 27%–96% of women with AGC–favor neoplasia [18,25–31,33–36]. Most women with a cytological result of AIS will have either biopsy-confirmed AIS (48%–69%) or invasive cervical adenocarcinoma (38%) [36,37].

Back to Top | Article Outline

Recommendations for Managing Women with AGC and AIS.

Initial Evaluation.

Colposcopy with endocervical sampling (seeAppendix 2) is recommended for women with all subcategories of AGC with the exception that women with atypical endometrial cells should initially be evaluated with endometrial sampling (seeAppendix 2)(AII). Endometrial sampling should be performed in conjunction with colposcopy in women over the age of 35 with AGC and younger women with AGC who have unexplained vaginal bleeding (AII) (Figure 4). Colposcopy with endocervical sampling is also recommended for women with a cytological result of AIS. Management of women with an initial result of AGC or AIS using a program of repeat cervical cytology is unacceptable (EII). There is currently insufficient data to allow an assessment of the use of HPV DNA testing in the management of women with AGC or AIS (CIII).

Figure 4.

Figure 4.

Back to Top | Article Outline
Subsequent Evaluation and Follow-up.

If invasive disease is not identified during the initial colposcopic workup, it is recommended that women with AGC, AGC–favor neoplasia, or AIS undergo a diagnostic excisional procedure (AII). The preferred diagnostic excisional procedure for women with AGC or AIS is cold-knife conization (BII). If biopsy-confirmed CIN (of any grade) is identified during the initial workup of a woman with AGC NOS, management should be according to the appropriate 2001 Consensus Guideline for the Management of Women with Cervical Histological Abnormalities (submitted for publication). If no neoplasia is identified during the initial workup of a woman with AGC NOS, it is recommended that the woman be followed using a program of repeat cervical cytology at 4- to 6-month intervals until four consecutive “negative for intraepithelial lesion or malignancy” cytology results are obtained, after which the woman may be returned to routine screening (BIII). If an ASC or LSIL result is obtained on any of the follow-up Pap tests, acceptable options include a repeat colposcopic examination or referral to a clinician experienced in the management of complex cytological situations (BIII). If an AGC or HSIL result is obtained on any of the follow-up Pap tests, acceptable options include a diagnostic excisional procedure or referral to a clinician experienced in the management of complex cytological situations (BIII).

Back to Top | Article Outline

Low-grade Squamous Intraepithelial Lesion

General Comments.

The median LSIL rate in the United States in 1996 was 1.6%. However, rates as high as 7.7% have been reported from laboratories serving high-risk populations [1,38]. There is a relatively poor correlation between the grade of lesion identified by cervical cytology and the grade of lesion that is identified on a colposcopically directed biopsy. Biopsy-confirmed CIN 2,3 is identified in approximately 15%–30% of women undergoing colposcopy for a cytological result of LSIL.

Back to Top | Article Outline

Recommendations for Managing Women with LSIL.

General Management Approaches.

Colposcopy is the preferred management of women with LSIL (AII) (Figure 5). Subsequent management options depend on whether a lesion is identified, whether the colposcopic examination is satisfactory, and whether the patient is pregnant, adolescent or postmenopausal.

Figure 5.

Figure 5.

Back to Top | Article Outline
Satisfactory Colposcopy.

Endocervical sampling is acceptable for nonpregnant women with a satisfactory colposcopy (seeAppendix 2) and a lesion identified in the transformation zone (CII), but it is preferred for nonpregnant women in whom no lesions are identified (CII). If biopsy-confirmed CIN is not identified and the colposcopy is satisfactory, acceptable management options include follow-up with repeat cytology at 6 and 12 months with a referral to colposcopy if a result of ASC-US or greater is obtained, or HPV DNA testing at 12 months with referral to colposcopy of all HPV DNA positive women (BII).

Back to Top | Article Outline
Unsatisfactory Colposcopy.

Endocervical sampling is preferred for nonpregnant women with an unsatisfactory colposcopy (AII). If biopsy-confirmed CIN is not identified and the colposcopy is unsatisfactory, acceptable management options include follow-up with repeat cytology at 6 and 12 months, or HPV DNA testing at 12 months (BII).

Women with LSIL who are found to have biopsy-confirmed CIN should be managed according to the appropriate 2001 Consensus Management Guideline.

Back to Top | Article Outline

LSIL in Special Circumstances

Postmenopausal Women.

In selected postmenopausal patients, follow-up without initial colposcopy using a protocol of follow-up with repeat cytology at 6 and 12 months with a referral to colposcopy threshold of ASC, or HPV DNA testing at 12 months is an acceptable option (CII) (Figure 6).

Figure 6.

Figure 6.

Providing a course of intravaginal estrogen followed by a repeat cervical cytology obtained approximately a week after completing the regimen is acceptable for women with ASC-US who have clinical or cytological evidence of atrophy with ASC-US and no contraindications to using intravaginal estrogen is an acceptable option. (CIII) If the repeat cervical cytology is “negative for squamous intraepithelial lesion or malignancy,” the cervical cytology should be repeated in 4 to 6 months. If both repeat cytology tests are “negative for squamous intraepithelial lesion or malignancy,” the patient can return to routine cytological screening; but if either repeat cytology is reported as ASC or greater, the patient should be referred for colposcopy. (BIII)

Back to Top | Article Outline
Adolescents.

In selected adolescents, follow-up without initial colposcopy using a protocol of follow up with repeat cytology at 6 and 12 months with a referral to colposcopy threshold of ASC, or HPV DNA testing at 12 months is an acceptable option (CII) (Figure 7).

Figure 7.

Figure 7.

Back to Top | Article Outline
Pregnant Women.

(See “HSIL in Special Circumstances: Pregnancy.”)

Back to Top | Article Outline

Diagnostic Excisional Procedures in Women with LSIL.

The routine use of diagnostic excisional procedures or ablative procedures is unacceptable for the initial management of patients with LSIL and either a satisfactory or unsatisfactory colposcopy in the absence of a biopsy-confirmed CIN. (DII)

Back to Top | Article Outline

High-grade Squamous Intraepithelial Lesion

Approaches to Managing Women with HSIL.

A cytological diagnosis of HSIL is relatively uncommon. The median rate of HSIL in the United States in 1996 was only 0.45%, according to a College of American Pathologists laboratory survey. [1] A cytological result of HSIL is a significant finding because it identifies a subset of women who are at relatively high-risk for harboring a CIN 2,3 or invasive cervical cancer. Approximately 70%–75% of women with HSIL will be found at colposcopy to have a biopsy-confirmed CIN 2,3, and 1%–2% will be found to have invasive cervical cancer [1,39].

Back to Top | Article Outline

Recommendations for Managing Women with HSIL.

General Management Approaches.

Colposcopy with endocervical assessment (seeAppendix 2) is the recommended management of women with HSIL. (AII) Subsequent management options depend on whether a lesion is identified, whether the colposcopic examination is satisfactory, whether the patient is pregnant, and whether immediate excision is appropriate (Figure 8).

Figure 8.

Figure 8.

Back to Top | Article Outline
Satisfactory Colposcopy.

When no lesion or only biopsy-confirmed CIN 1 is identified after colposcopy in women with HSIL and a satisfactory colposcopy, it is recommended that, when possible, a review of the cytology, colposcopy and histology be performed. (BIII) If the review yields a revised interpretation, management should follow guidelines for the revised interpretation; if a cytological interpretation of HSIL is upheld or review is not possible, a diagnostic excisional procedure is preferred in nonpregnant patients. (BII) A colposcopic reevaluation with endocervical assessment is acceptable in special circumstances (see HSIL in Special Circumstances). (BIII)

Back to Top | Article Outline
Unsatisfactory Colposcopy.

When no lesion is identified after colposcopy in women with HSIL and an unsatisfactory colposcopy, a review of the cytology, colposcopy and histology should be performed when possible. (BIII) If the review yields a revised interpretation, management should follow guidelines for the revised interpretation. If a cytological interpretation of HSIL is upheld, review is not possible, or a biopsy-confirmed CIN 1 is identified, a diagnostic excisional procedure is recommended in nonpregnant patients. (AII) Ablation is unacceptable. (EII)

Omission of endocervical sampling is acceptable when a diagnostic excisional procedure is planned. In women with HSIL and a colposcopic impression of a high-grade lesion, initial evaluation utilizing a diagnostic excisional procedure is also an acceptable option. (BI) Triage utilizing either a program of repeat cytology or HPV DNA testing is unacceptable. (EII) Women with HSIL who are found to have biopsy-confirmed CIN should be managed according the appropriate 2001 Consensus Guideline for the Management of Women with Cervical Histological Abnormalities (submitted for publication).

Back to Top | Article Outline

HSIL in Special Circumstances.

Pregnancy.

It is preferred that the colposcopic evaluation of pregnant women with HSIL be conducted by clinicians who are experienced in the evaluation of colposcopic changes induced by pregnancy. (BIII) Biopsy of lesions suspicious for high-grade disease or cancer is preferred; biopsy of other lesions is acceptable. (BIII) Endocervical curettage is unacceptable in pregnant women. (EIII) Since unsatisfactory colposcopy may become satisfactory as the pregnancy progresses, it is recommended that women with an unsatisfactory colposcopy undergo a repeat colposcopic examination in 6 to 12 weeks. (BIII) In the absence of invasive disease, additional colposcopic and cytological examinations are recommended, with biopsy only if the appearance of the lesion worsens or cytology suggests invasive cancer. (BII) Unless invasive cancer is identified, treatment is unacceptable. (EII) A diagnostic excisional procedure is recommended only if invasion is suspected. (BII) Reevaluation with cytology and colposcopy is recommended no sooner than 6 weeks postpartum. (CIII)

Back to Top | Article Outline
Young Women of Reproductive Age.

When biopsy-confirmed CIN 2,3 is not identified in a young woman with a HSIL cytology, observation with colposcopy and cytology at 4- to 6-month intervals for one year is acceptable, provided colposcopy is satisfactory, endocervical sampling is negative, and the patient accepts the risk of occult disease. If a lesion appears to progress to a colposcopic high-grade lesion or HSIL cytology persists, a diagnostic excisional procedure is recommended. (BIII)

Back to Top | Article Outline

Acknowledgments

The development of the 2001 Consensus Guidelines was supported by ASCCP and a grant, No. 1 R13 CA96190–01, from the National Cancer Institute. The content of the guidelines is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute. The ASCCP would like to thank Ms. Kathy Poole for administrative support for the conference and the development of the guidelines.

Back to Top | Article Outline

FOOTNOTES

*Indications in bold throughout guidelines refer to Table 1.
Cited Here...

**Participants include gynecologists, gynecological oncologists, family physicians, cytopathologists, cytotechnologists, epidemiologists, health policy experts, lawyers, nurse clinicians, social scientists, and pathologists.

Back to Top | Article Outline

APPENDIX 1 Participants and Participating Organizations

Organizer.

American Society for Colposcopy and Cervical Pathology (ASCCP)

Back to Top | Article Outline

Steering Committee.

J. Thomas Cox, MD, University of California, Santa Barbara, Santa Barbara, CA; Stu Massad, MD, Cook County Hospital, Chicago, IL; Leo Twiggs, MD, University of Miami School of Medicine, Miami, FL; Edward Wilkinson, MD, chair, University of Florida College of Medicine, Gainesville, FL; and Thomas C. Wright, Jr., MD, Columbia University, New York, NY.

Back to Top | Article Outline

ASC Committee.

Barbara Apgar, MD, University of Michigan, Ann Arbor, MI; Carmel Cohen, MD, Mount Sinai Medical Center, New York, NY; Walter Kinney, MD, cochair, University of California, Davis, and Permanente Medical Group, Sacramento, CA; Hershel Lawson, MD, Centers for Disease Control and Prevention, Atlanta, GA; Mark Schiffman, MD, MPH, National Cancer Institute, Bethesda, MD; Mark Sherman, MD, National Cancer Institute, Bethesda, MD; Pamela Stratton, MD, National Institute of Child Health and Human Development, Rockville, MD; Cornelia Trimble, MD, Johns Hopkins University, Baltimore, MD; Leslie Walton, MD, University of North Carolina School of Medicine, Chapel Hill, NC; and Thomas C. Wright, Jr., MD, cochair, Columbia University, New York, NY.

Back to Top | Article Outline

AGC Committee.

Raheela Ashfaq, MD, University of Texas Southwestern, Dallas, TX; R. Marshall Austin, MD, PhD, cochair, Medical University of South Carolina, Charleston, SC; J. Thomas Cox, MD, cochair, University of California, Santa Barbara, CA; Francisco Garcia, MD, MPH, University of Arizona Health Sciences Center, Tucson, AZ; Diane Harper, MD, MPH, Dartmouth-Hitchcock Medical Center, Hanover, NH; Kenneth Noller, MD, Tuft's University Medical Center, Boston, MA; Thomas Purdon, MD, University of Arizona Health Sciences Center, Tucson, AZ; Ellen Sheets, MD, Brigham and Women's Hospital, Boston, MA; Ralph Richart, MD, Columbia University, New York, NY; Ted Trimble, MD, MPH, National Cancer Institute, Bethesda, MD; and V. Cecil Wright, MD, University of Western Ontario, London, Ontario, Canada.

Back to Top | Article Outline

LSIL Committee.

Marluce Bibbo, MD, Thomas Jefferson University Hospital, Philadelphia, PA; Terrance Colgan, MD, Mount Sinai Hospital, Toronto, Ontario, Canada; Terri Cornelison, MD, National Cancer Institute, Bethesda, MD; Daron Ferris, MD, Medical College of Georgia, Augusta, GA; Kenneth Hatch, MD, cochair, Arizona Cancer Center, Tucson, AZ; Edward Partridge, MD, University of Alabama at Birmingham, Birmingham, AL; Mark Spitzer, MD, North Shore University Hospital, Manhasset, NY; Claudia Werner, MD, University of Texas Southwestern, Dallas, TX; Alan Waxman, MD, University of New Mexico, Albuquerque, NM; and Edward Wilkinson, MD, cochair, University of Florida College of Medicine, Gainesville, FL.

Back to Top | Article Outline

HSIL Committee.

Lou Benedet, MD, University of British Columbia, Vancouver, British Columbia, Canada; Jay Carlson, DO, cochair, Walter Reed Army Medical Center, Washington, DC; Chris Crum, MD, Brigham and Women's Hospital, Boston, MA; Juan Felix, MD, LAC-USC Medical Center, Los Angeles, CA; Verda Hunter, MD, Resource Center for Gynecologic Oncology, Kansas City, MO; Burton Krumholz, MD, Long Island Jewish Medical Center, New Hyde Park, NY; Neal Lonky, MD, MPH, Kaiser Permanente, Yorba Linda, CA; Stu Massad, MD, Cook County Hospital, Chicago, IL; Luis Padilla, MD, University of New Mexico, Albuquerque, NM; and Leo Twiggs, MD, cochair, University of Miami School of Medicine, Miami, FL.

Back to Top | Article Outline

Participants.

**

Fadi Abdul-Karim, MD, University Hospitals of Cleveland, Cleveland, OH; Barbara Bennett, MD, University of Florida, Gainesville, FL; Guy Benrubi, MD, University of Florida at Jacksonville, Jacksonville, FL; Jonathan Berek, MD, UCLA School of Medicine, Los Angeles, CA; Christine Bergeron, MD, Laboratoire Pasteur-CERBA, Paris, France; Monique Bertrand, MD, Vancouver Hospital and Health Sciences Center, Vancouver, British Columbia, Canada; George Birdsong, MD, Emory University, Atlanta, GA; Patricia Braly, MD, Lakeside Hospital, New Orleans, LA; Henry Buck, MD, University of Kansas, Lawrence, KS; Louis Burke, MD, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA; David Chhieng, MD, University of Alabama, Birmingham, AL; Edmund Cibas, MD, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; William Creasman, MD, Medical University of South Carolina, Charleston, SC; Christopher P. Crum, MD, Harvard Medical School, Boston, MA; Teresa Darragh, MD, University of California, San Francisco, CA; Diane Davey, MD, University of Kentucky, Lexington, KY; Santiago Dexeus, MD, Institut Universitari Dexeus, Barcelona, Spain; Charles Dunton, MD, Thomas Jefferson University Hospital, Philadelphia, PA; Paul Elgert, CT, New York University School of Medicine, New York, NY; Alex Ferenczy, MD, McGill University, Sir Mortimer B. Davis Jewish Central Hospital, Montreal, Quebec, Canada; Catterina Ferreccio, MD, MPH, Pan American Health Organization, Washington, DC; Lisa Flowers, MD, Emory University, Atlanta, GA; William Frable, MD, Virginia Commonwealth University, Richmond, VA; Dr. Joseph Fraumeni, National Cancer Institute, Bethesda, MD; Robert Gay, CT, APL School of Cytotechnology, Las Vegas, NV; Melvin Gerbie, MD, Northwestern University Medical School, Chicago, IL; Sue Goldie, MD, MPH, Harvard Center for Risk Analysis, Boston, MA; Ben Greer, MD, University of Washington Medical Center, Seattle, WA; Richard Guido, MD, Magee Women's Hospital, Pittsburgh, PA; Fernando Guijon, MD, University of Manitoba, Winnipeg, Manitoba, Canada; Hope Haefner, MD, University of Michigan, Ann Arbor, MI; Vivien Hanson, MD, University of Washington, Seattle, WA; Michael Henry, MD, University of Maryland, Baltimore, MD; Robert Hilgers, MD, University of Louisville, Louisville, KY; Angela Houghton, MD, American Medical Women's Association, Alexandria, VA; Lydia Howell, MD, University of California, Davis, Sacramento, CA; Howard W. Jones III, MD, Vanderbilt University, Nashville, TN; Thomas M. Julian, MD, University of Wisconsin, Madison, WI; Raymond H. Kaufman, MD, Baylor School of Medicine, Houston, TX; Gordon M. Lickrish, MD, University of Toronto, Toronto, Ontario, Canada; Louise Magruder, Food and Drug Administration, Rockville, MD; Edward J. Mayeaux, MD, Louisiana State University Health Sciences Center, Shreveport, LA; Dennis McCoy, Esq., Saperston & Day, PC, Buffalo, NY; Larry McGowan, MD, George Washington University, Washington, DC; Kathy McIntyre-Seltman, MD, Magee Women's Hospital, Pittsburgh, PA; James McNeil, Jr. MD, Naval Hospital, Jacksonville, FL; Joseph Monsonego, MD, Eurogin, Paris, France; Ann Moriarty, MD, AmeriPath Indiana, Indianapolis, IN; Anna-Barbara Moscicki, MD, University of California, San Francisco, CA; Dr. Joan Murphy, Princess Margaret Hospital, Toronto, Ontario, Canada; Dennis O'Connor, MD, University of Louisville School of Medicine, Louisville, KY; Marianne U. Prey, MD, Quest Diagnostics, Inc., St. Louis, MO; Stephen Raab, MD, Allegheny General Hospital, Pittsburgh, PA; Max Robinowitz, MD, Food and Drug Administration, Rockville, MD; Dorothy Rosenthal, MD, Johns Hopkins University, Baltimore, MD; Michel Roy, MD, Laval University, Quebec City, Quebec, Canada; Mary Rubin, PhD, CRNP, Education Programs Associates, Sausalito, CA; Carolyn Runowicz, MD, Albert Einstein College of Medicine, Montefiore Medical Center, New York, NY; Michael Shier, MD, University of Toronto, Toronto, Ontario, Canada; Mary Sidawy, MD, George Washington University, Washington, DC; Albert Singer, MD, Whittington Hospital, London, England; Robert Smith, PhD, American Cancer Society, Atlanta, GA; Diane Solomon, National Cancer Institute, Bethesda, MD; Dr. Gerald Stanimir, Royal Victoria Hospital, Montreal, Quebec, Canada; Mark Stoler, MD, University of Virginia Health Sciences Center, Charlottesville, VA; Sana Tabbara, MD, George Washington University, Washington, DC; Cornelia Trimble, MD, Johns Hopkins University, Baltimore, MD; Ted Trimble, MD, MPH, National Cancer Institute, Bethesda, MD; Jeffrey Waldman, MD, Planned Parenthood Shasta-Diablo, Concord, CA; Eric Wall, MD, MPH, Premera Blue Cross, Oregon Health Sciences University, Portland, OR; Joan Walker, MD, University of Oklahoma, Oklahoma City, OK; Bethany Weaver, DO, University of Washington, Seattle, WA; Edward Wiesmeier, MD, UCLA, Los Angeles, CA; Dorothy Wiley, PhD, UCLA School of Nursing, Los Angeles, CA; Edward Wilkinson, MD, University of Florida College of Medicine, Gainesville, FL; Gerald Willett, MD, Food and Drug Administration, Rockville, MD; Barbara Winkler, MD, Quest Diagnostics, Inc., Tetenboro, NJ; Cheryl Wiseman, MPH, CT, Centers for Medicaid and Medicare Services, Baltimore, MD; Susan Wysocki, RNC, NP, National Association for Nurse Practitioners in Women's Health, Washington, DC; Nancy Young, MD, Fox Chase Cancer Center, Philadelphia, PA; Lauren Zoschnick, MD, University of Michigan, Ann Arbor, MI; and Rosemary Zuna, MD, University of Oklahoma Health Sciences Center, Oklahoma City, OK.

Back to Top | Article Outline

Participating Organizations.

Agency for Health Care Research and Quality; American Academy of Family Physicians; American Cancer Society; American College Health Association; American College of Obstetricians and Gynecologists; American Medical Women's Association; American Social Health Association; American Society for Clinical Pathologists; American Society for Colposcopy and Cervical Pathology; American Society of Cytopathology; Association of Reproductive Health Professionals; Centers for Disease Control and Prevention, Division of Cancer Prevention and Control; Centers for Disease Control and Prevention, Division of Laboratory Systems; Centers for Medicaid and Medicare Services; College of American Pathologists; Eurogin; Food and Drug Administration; International Federation for Cervical Pathology and Colposcopy; International Gynecologic Cancer Society; International Society of Gynecological Pathologists; National Cancer Institute; National Association of Nurse Practitioners in Women's Health; Papanicolaou Society; Pan American Health Organization; Planned Parenthood Federation of America; Society of Canadian Colposcopists; Society of Gynecologic Oncologists; and Society of Obstetricians & Gynaecologists of Canada.

Back to Top | Article Outline

APPENDIX 2 Definitions of Terms

Colposcopy is the examination of the cervix, vagina, and, in some instances, the vulva with a colposcope after the application of a 3%–5% acetic acid solution coupled with obtaining colposcopically directed biopsies of all lesions suspected of representing neoplasia.

Endocervical sampling includes obtaining a specimen either for histological evaluation, using an endocervical curette or a cytobrush, or for cytological evaluation, using a cytobrush.

Endocervical assessment is the process of evaluating the endocervical canal for the presence of neoplasia, using either a colposcope or endocervical sampling.

Diagnostic excisional procedure is the process of obtaining a specimen from the transformation zone and endocervical canal for histological evaluation and includes laser conization, cold-knife conization, loop electrosurgical excision (LEEP), and loop electrosurgical conization.

Satisfactory colposcopy indicates that the entire squamocolumnar junction and the margin of any visible lesion can be visualized with the colposcope.

Endometrial sampling includes obtaining a specimen for histological evaluation, using an endometrial biopsy or a “dilation and curettage” or hysteroscopy.

Back to Top | Article Outline

REFERENCES

1. Jones BA, Davey DD. Quality management in gynecologic cytology using interlaboratory comparison. Arch Pathol Lab Med 2000; 124: 672 – 81.
2. Jones HW. The Bethesda System. Cancer 1995; 76 (suppl): 1914 – 18.
3. Solomon D, Davey DD, Moriarty A, et al. Bethesda 2001: Terminology for reporting the results of cervical cytology. JAMA 2002;285.
3a. Solomon D, Schiffman M, Rarone R. ASCUS LSIL Triage Study (ALTS) conclusions reaffirmed: response to a November 2001 commentary. Obstet Gynecol 2002; 99: 671 – 4.
4. Manos MM, Kinney WK, Hurley LB, Sherman ME, Shieh-Ngai J, Kurman RJ, et al. Identifying women with cervical neoplasia: Using human papillomavirus DNA testing for equivocal Papanicolaou results. JAMA 1999; 281: 1605 – 10.
5. Solomon D, Schiffman M, Tarrone R. Comparison of three management strategies for patients with atypical squamous cells of undetermined significance: baseline results from a randomized trial. J Natl Cancer Inst 2001; 93: 293 – 9.
6. Wright Jr., TC, Lorincz A, Ferris DG, Richart RM, Ferenczy A, Mielzynska I, et al. Reflex human papillomavirus deoxyribonucleic acid testing in women with abnormal Papanicolaou smears. Am J Obstet Gynecol 1998; 178: 962 – 6.
7. Wright TC, Cox JT, Massad LS, Twiggs LB, Wilkinson EJ. 2001 consensus guidelines for the management of women with cervical cytological abnormalities and cervical cancer precursors: Part I: Cytological abnormalities. JAMA 2002;284.
8. Gross PA, Barrett TL, Dellinger EP, Krause PJ, Martone WJ, McGowan Jr, JE et al. Purpose of quality standards for infectious diseases. Infectious Diseases Society of America. Clin Infect Dis 1994; 18: 421.
9. Kish MA. Guide to development of practice guidelines. Clin Infect Dis 2001; 32: 851 – 4.
10. USPHS/IDSA guidelines for the prevention of opportunistic infections in persons infected with human immunodeficiency virus. Morbidity Mortality Weekly Report 1999;48(No.RR-10)1–26.
11. Wright TC, Ferenczy AF, Kurman RJ. Precancerous lesions of the cervix. In: Kurman RJ, ed. Blaustein's Pathology of the Female Genital Tract. 4th ed. New York: Springer-Verlag; 1994: 229 – 78.
12. Robb JA. The “ASCUS” swamp. Diagn Cytopathol. 1994; 11: 319 – 20.
13. Sherman ME, Schiffman MH, Lorincz AT, Manos MM, Scott DR, Kuman RJ, et al. Toward objective quality assurance in cervical cytopathology. Correlation of cytopathologic diagnoses with detection of high-risk human papillomavirus types. Am J Clin Pathol 1994; 102: 182 – 7.
14. Stoler MH, Schiffman M. Interobserver reproducibility of cervical cytologic and histologic interpretations: realistic estimates from the ASCUS-LSIL Triage Study. JAMA 2001; 285: 1500 – 5.
15. Slawson DC, Bennett JH, Simon LJ, Herman JM. Should all women with cervical atypia be referred for colposcopy: A HARNET study. J Fam Pract 1994; 38: 387 – 92.
16. Kobelin MH, Kobelin CG, Burke L, Lavin P, Niloff JM, Kim YB. Incidence and predictors of cervical dysplasia in patients with minimally abnormal Papanicolaou smears. Obstet Gynecol 1998; 92: 356 – 9.
17. Eskridge C, Begneaud WP, Landwehr C. Cervicography combined with repeat Papanicolao U test as triage for low-grade cytologic abnormalities. Obstet Gynecol 1998; 92: 351 – 5.
18. Jones BA, Novis DA. Follow-up of abnormal gynecologic cytology: A college of American pathologists Q-probes study of 16132 cases from 306 laboratories. Arch Pathol Lab Med 2000; 124: 665 – 71.
19. Lonky NM, Sadeghi M, Tsadik GW, Petitti D. The clinical significance of the poor correlation of cervical dysplasia and cervical malignancy with referral cytologic results. Am J Obstet Gynecol 1999; 181: 560 – 6.
20. Crum CP, Genest DR, Krane JF, Hogan C, Sun D, Bellerose B, et al. Subclassifying atypical squamous cells in Thin-Prep cervical cytology correlates with detection of high-risk human papillomavirus DNA. Am J Clin Pathol 1999; 112: 384 – 90.
21. Schoolland M, Sterrett GF, Knowles SA, Mitchell KM, Kurinczuk JJ. The “Inconclusive-possible high grade epithelial abnormality” category in Papanicolaou smear reporting. Cancer 1998; 84: 208 – 17.
22. Malik SN, Wilkinson EJ, Drew PA, Bennett BB, Hardt NS. Do qualifiers of ASCUS distinguish between low- and high-risk patients? Acta Cytol 1999; 43: 376 – 80.
23. Sherman ME, Solomon D, Schiffman M. Qualification of ASCUS: A comparison of equivocal LSIL and equivocal HSIL cervical cytology in the ASCUS LSIL Triage Study (ALTS). Am J Clin Pathol. In press.
24. Quddus MR, Sung CJ, Steinhoff MM, Lauchlan SC, Singer DB, Hutchinson ML. Atypical squamous metaplastic cells: Reproducibility, outcome, and diagnostic features on ThinPrep Pap test. Cancer 2001; 93: 16 – 22.
25. Ronnett BM, Manos MM, Ransley JE, Fetterman BJ, Kinney WK, Hurley LB, et al. Atypical glandular cells of undetermined significance (AGUS): Cytopathologic features, histopathologic results, and human papillomavirus DNA detection. Hum Pathol 1999; 30: 816 – 25.
26. Kennedy AW, Salmieri SS, Wirth SL, Biscotti CV, Tuason LJ, Travarca MJ. Results of the clinical evaluation of atypical glandular cells of undetermined significance (AGCUS) detected on cervical cytology screening. Gynecol Oncol 1996; 63: 14 – 8.
27. Valdini A, Vaccaro C, Pechinsky G, Abernathy V. Incidence and evaluation of an AGUS Papanicolaou smear in primary care. J Am Board Fam Pract 2001; 14: 172 – 7.
28. Duska LR, Flynn CF, Chen A, Whall-Strojwas D, Goodman A. Clinical evaluation of atypical glandular cells of undetermined significance on cervical cytology. Obstet Gynecol 1998; 91: 278 – 82.
29. Taylor RR, Guerrieri JP, Nash JD, Henry MR, O'Connor DM. Atypical cervical cytology. Colposcopic follow-up using the Bethesda System. J Reprod Med 1993; 38: 443 – 7.
30. Goff BA, Atanasoff P, Brown E, Muntz HG, Bell DA, Rice LW. Endocervical glandular atypia in Papanicolaou smears. Obstet Gynecol 1992; 79: 101 – 4.
31. Zweizig S, Noller K, Reale F, Collis S, Resseguie L. Neoplasia associated with atypical glandular cells of undetermined significance on cervical cytology. Gynecol Oncol 1997; 65: 314 – 8.
32. Obenson K, Abreo F, Grafton WD. Cytohistologic correlation between AGUS and biopsy-detected lesions in postmenopausal women. Acta Cytol 2000; 44: 41 – 5.
33. Soofer SB, Sidawy MK. Atypical glandular cells of undetermined significance: Cinically significant lesions and means of patient follow-up. Cancer 2000; 90: 207 – 4.
34. Eddy GL, Wojtowycz MA, Piraino PS, Mazur MT. Papanicolaou smears by the Bethesda system in endometrial malignancy: Utility and prognostic importance. Obstet Gynecol 1997; 90: 999 – 1003.
35. Veljovich DS, Stoler MH, Andersen WA, Covell JL, Rice LW. Atypical glandular cells of undetermined significance: A five-year retrospective histopathologic study. Am J Obstet Gynecol 1998; 179: 382 – 90.
36. Chhieng DC, Elgert P, Cohen JM, Cangiarella JF. Clinical significance of atypical glandular cells of undetermined significance in postmenopausal women. Cancer 2001; 93: 1 – 7.
37. Lee KR, Manna EA, St John T. Atypical endocervical glandular cells: accuracy of cytologic diagnosis. Diagn Cytopathol 1995; 13: 202 – 8.
38. Takezawa K, Bennett BB, Wilkinson EJ, Drew PA, Hardt NS. Squamous intraepithelial lesions of the cervix in a high-risk population. J Lower Gen Tract Dis 1998; 2: 136 – 40.
39. Kinney WK, Manos MM, Hurley LB, Ransley JE. Where's the high-grade cervical neoplasia? The importance of minimally abnormal Papanicolaou diagnoses. Obstet Gynecol 1998; 91: 973 – 6.
©2002The American Society for Colposcopy and Cervical Pathology