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

Abstract

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. 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: Rating the Recommendations2001 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. 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. 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.: Management of Women with Atypical Squamous Cells of Undetermined Significance (ASC-US)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). 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.: Management of Women with Atypical Squamous Cells of Undetermined Significance (ASC-US) In Special CircumstancesImmunosuppressed 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. Pregnant Patients. It is recommended that pregnant women with ASC-US be managed in the same manner as nonpregnant women (BIII). 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.: Management of Women with Atypical Squamous Cells: Cannot Exclude High-grade SIL (ASC - H)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. 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]. 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.: Management of Women with Atypical Glandular Cells (AGC)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). 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. 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.: Management of Women with Low-grade Squamous Intraepithelial Lesions (LSIL)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). 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. 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.: Management of Women with Low-grade Squamous Intraepithelial Lesions In Special CircumstancesProviding 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) 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.: Management of Women with Low-grade Squamous Intraepithelial Lesions In Special CircumstancesPregnant Women. (See “HSIL in Special Circumstances: Pregnancy.”) 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) 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]. 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.: Management of Women with High-grade Squamous Intraepithelial Lesions (HSIL)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) 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). 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) 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) 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.