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2006 consensus guidelines for the management of women with abnormal cervical cancer screening tests

2007; Elsevier BV; Volume: 197; Issue: 4 Linguagem: Inglês

10.1016/j.ajog.2007.07.047

1097-6868

Thomas C. Wright, L. Stewart Massad, Charles J. Dunton, Mark Spitzer, Edward J. Wilkinson, Diane Solomon,

Genital Health and Disease

A group of 146 experts representing 29 organizations and professional societies met September 18-19, 2006, in Bethesda, MD, to develop revised evidence-based, consensus guidelines for managing women with abnormal cervical cancer screening tests. Recommendations for managing atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesion (LSIL) are essentially unchanged. Changes were made for managing these conditions in adolescents for whom cytological follow-up for 2 years was approved. Recommendations for managing high-grade squamous intraepithelial lesion (HSIL) and atypical glandular cells (AGC) also underwent only minor modifications. More emphasis is placed on immediate screen-and-treat approaches for HSIL. Human papillomavirus (HPV) testing is incorporated into the management of AGC after their initial evaluation with colposcopy and endometrial sampling. The 2004 Interim Guidance for HPV testing as an adjunct to cervical cytology for screening in women 30 years of age and older was formally adopted with only very minor modifications. A group of 146 experts representing 29 organizations and professional societies met September 18-19, 2006, in Bethesda, MD, to develop revised evidence-based, consensus guidelines for managing women with abnormal cervical cancer screening tests. Recommendations for managing atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesion (LSIL) are essentially unchanged. Changes were made for managing these conditions in adolescents for whom cytological follow-up for 2 years was approved. Recommendations for managing high-grade squamous intraepithelial lesion (HSIL) and atypical glandular cells (AGC) also underwent only minor modifications. More emphasis is placed on immediate screen-and-treat approaches for HSIL. Human papillomavirus (HPV) testing is incorporated into the management of AGC after their initial evaluation with colposcopy and endometrial sampling. The 2004 Interim Guidance for HPV testing as an adjunct to cervical cytology for screening in women 30 years of age and older was formally adopted with only very minor modifications. Since the publication of the 2001 consensus guidelines, new information has become available, which includes the key follow-up results from the National Cancer Institute (NCI)–sponsored ASCUS (atypical squamous cells of undetermined significance)/LSIL (low-grade squamous intraepithelial lesions) Triage Study (ALTS).1ASCUS-LSIL Triage Study (ALTS) GroupResults of a randomized trial on the management of cytology interpretations of atypical squamous cells of undetermined significance.Am J Obstet Gynecol. 2003; 188: 1383-1392PubMed Google Scholar, 2ASCUS-LSIL Triage Study (ALTS) GroupA randomized trial on the management of low-grade squamous intraepithelial lesion cytology interpretations.Am J Obstet Gynecol. 2003; 188: 1393-1400PubMed Google Scholar Moreover, molecular testing for high-risk types of human papillomavirus (HPV) is being used together with cervical cytology for screening in women 30 years of age and older. Although “interim guidance” for the use of HPV DNA testing in the screening setting was proposed in 2004, recommendations for how to manage the combination of test results have not formally been evaluated by a large, multidisciplinary group.3Wright Jr, T.C. Schiffman M. Solomon D. et al.Interim guidance for the use of human papillomavirus DNA testing as an adjunct to cervical cytology for screening.Obstet Gynecol. 2004; 103: 304-309Crossref PubMed Scopus (447) Google Scholar Once the 2001 guidelines were implemented in a variety of clinical settings, it became apparent that there were a number of areas in which changes were needed. This pertains particularly to special populations such as adolescents and postmenopausal women. Therefore, in 2005, the American Society for Colposcopy and Cervical Pathology (ASCCP), together with its partner professional societies and federal and international organizations (listed in Appendix A), began the process of revising the guidelines. This culminated in the 2006 consensus conference that was held at the National Institutes of Health in September 2006. This report provides the recommendations developed with respect to managing women with cytological abnormalities. Recommendations for managing women with cervical intraepithelial neoplasia (CIN) or adenocarcinoma in situ (AIS) appear in the accompanying article. A more comprehensive discussion of the recommendations and their supporting evidence will be made available on the ASCCP website (www.asccp.org).See related editorial, page 337, and related article, page 340Guideline Development ProcessThe process used to develop the 2006 Consensus Guidelines was similar to that for the previous guidelines and is discussed in depth in other publications.4Wright Jr, T.C. Cox J.T. Massad L.S. Twiggs L.B. Wilkinson E.J. 2001 consensus guidelines for the management of women with cervical cytological abnormalities.JAMA. 2002; 287: 2120-2129Crossref PubMed Scopus (1070) Google Scholar, 5Wright T.C. Massad L.S. Dunton C.J. Spitzer M. Wilkinson E.J. Solomon D. 2006 consensus guidelines for the management of women with abnormal cervical cancer screening tests.J Low Genit Tract Dis. 2007; (in press.)Google Scholar Guidelines were developed through a multistep process. Working groups reviewed literature published after 2000 before developing guidelines that were subsequently revised based on input from the professional community at large, obtained using an Internet-based bulletin board. At the consensus conference, guidelines with supporting evidence were presented and underwent discussion, revision, and approval. The terminology utilized in the new guidelines is identical to that used previously, as is the 2-part rating system (Table).4Wright Jr, T.C. Cox J.T. Massad L.S. Twiggs L.B. Wilkinson E.J. 2001 consensus guidelines for the management of women with cervical cytological abnormalities.JAMA. 2002; 287: 2120-2129Crossref PubMed Scopus (1070) Google Scholar, 5Wright T.C. Massad L.S. Dunton C.J. Spitzer M. Wilkinson E.J. Solomon D. 2006 consensus guidelines for the management of women with abnormal cervical cancer screening tests.J Low Genit Tract Dis. 2007; (in press.)Google Scholar The terms “recommended,” “preferred,” “acceptable,” and “unacceptable” are used in the guidelines to describe various interventions. The letters A through E are used to indicate strength of recommendation for or against the use of a particular option. Roman numerals I-III are used to indicate the “quality of evidence” for a given recommendation. The “strength of recommendation” and “quality of evidence” are provided in parentheses after each recommendation.TABLERating the recommendationsStrength of Recommendation⁎Modified from references.80,81 AGood evidence for efficacy and substantial clinical benefit support recommendation for use. BModerate evidence for efficacy or only limited clinical benefit supports recommendation for use. CEvidence for efficacy is insufficient to support a recommendation for or against use, but recommendations may be made on other grounds. DModerate evidence for lack of efficacy or for adverse outcome supports a recommendation against use. EGood evidence for lack of efficacy or for adverse outcome supports a recommendation against use.Quality of Evidence⁎Modified from references.80,81 IEvidence from at least 1 randomized, controlled trial. IIEvidence from at least 1 clinical trial without randomization, from cohort or case-controlled analytic studies (preferably from more than 1 center) or from multiple time-series studies or dramatic results from uncontrolled experiments. IIIEvidence from opinions of respected authorities based on clinical experience, descriptive studies, or reports of expert committees.Terminology used for recommendations†The assignment of these terms represents an opinion ratified by vote by the Consensus Conference. RecommendedGood data to support use when only 1 option is available. PreferredOption is the best (or 1 of the best) when there are multiple other options AcceptableOne of multiple options when there are either data indicating that another approach is superior or when there are no data to favor any single option. UnacceptableGood data against use. Modified from references.80Gross P.A. Barrett T.L. Dellinger E.P. et al.Purpose of quality standards for infectious diseases Infectious Diseases Society of America.Clin Infect Dis. 1994; 18: 421Crossref PubMed Scopus (96) Google Scholar, 81Kish M.A. Guide to development of practice guidelines.Clin Infect Dis. 2001; 32: 8511Crossref Scopus (245) Google Scholar† The assignment of these terms represents an opinion ratified by vote by the Consensus Conference. Open table in a new tab 2006 Consensus GuidelinesGeneral commentsAlthough the guidelines are based on evidence whenever possible, for certain clinical situations, there is limited high-quality evidence, and in these situations the guidelines have, by necessity, been based on consensus expert opinion. It is also important to recognize that these guidelines should never substitute for clinical judgment. Clinical judgment should always be used when applying a guideline to an individual patient because it is impossible to develop guidelines that apply to all situations.The 2001 Bethesda System terminology is used for cytologic classification.6Solomon D. Davey D. Kurman R. et al.The 2001 Bethesda System: terminology for reporting results of cervical cytology.JAMA. 2002; 287: 2114-2119Crossref PubMed Scopus (2642) Google Scholar This terminology utilizes the terms low-grade squamous intraepithelial lesion (LSIL) and high-grade squamous intraepithelial lesion (HSIL) to refer to low-grade lesions and high-grade cervical cancer precursors, respectively. The histologic classification used is a 2-tiered system that applies the terms CIN 1 to low-grade lesions and CIN 2,3 to high-grade precursors. It is important to note that cytologic LSIL is not equivalent to histologic CIN 1 and cytologic HSIL is not equivalent to histologic CIN 2,3. Algorithms detailing the different management recommendations are available at the ASCCP website (www.asccp.org). A glossary of terms used in the guidelines is in Appendix B.The current guidelines expand clinical indications for HPV testing based on studies using validated HPV assays. One cannot assume that management decisions that are based on results of HPV tests that have not been similarly validated will result in the outcomes that are intended by these guidelines. Furthermore, the application of these guidelines using such tests may increase the potential for patient harm. The appropriate use of these guidelines requires that laboratories utilize only HPV tests that have been analytically and clinically validated with proven acceptable reproducibility, clinical sensitivity, specificity, and positive and negative predictive values for cervical cancer and verified precancer (CIN 2,3), as documented by Food and Drug Administration (FDA) approval and/or publication in peer-reviewed scientific literature. It is also important to stress that testing should be restricted to high-risk (oncogenic) HPV types.7Cogliano V. Baan R. Straif K. Grosse Y. Secretan B. El Ghissassi F. Carcinogenicity of human papillomaviruses.Lancet Oncol. 2005; 6: 204Abstract Full Text Full Text PDF PubMed Scopus (569) Google Scholar, 8Wright T.C. Schiffman M. Adding a test for human papillomavirus DNA to cervical-cancer screening.N Engl J Med. 2003; 348: 489-490Crossref PubMed Scopus (208) Google Scholar Testing for low-risk (nononcogenic) HPV types has no role in the evaluation of women with abnormal cervical cytological results. Therefore, whenever “HPV testing” is referred to in the guidelines, it applies only to testing for high-risk (oncogenic) HPV types.Special populationsThe exact same cytologic result has a different risk of CIN 2,3 or cancer (CIN 2+) in various groups of women. One such special population is adolescent women (aged 20 years and younger) who have a high prevalence of HPV infections, more minor-grade cytologic abnormalities (atypical squamous cells [ASC] and LSIL) but very low risk for invasive cervical cancer, compared with older women.9SEER Cancer Statistics Review 1975-2003. Vol 2006. National Institutes of Health, Bethesda, MD2006Google Scholar, 10Insinga R.P. Glass A.G. Rush B.B. Diagnoses and outcomes in cervical cancer screening: a population-based study.Am J Obstet Gynecol. 2004; 191: 105-113Abstract Full Text Full Text PDF PubMed Scopus (189) Google Scholar This is because the vast majority of HPV infections spontaneously clear within 2 years after infection and are of little long-term clinical significance.11Moscicki A.B. Schiffman M. Kjaer S. Villa L.L. Updating the natural history of HPV and anogenital cancer Chapter 5.Vaccine. 2006; 24: S42-S51Crossref Scopus (393) Google Scholar, 12Burchell A.N. Winer R.L. de Sanjose S. Franco E.L. Epidemiology and transmission dynamics of genital HPV infection Chapter 6.Vaccine. 2006; 24: S52-S61Crossref Scopus (390) Google Scholar Therefore, performing colposcopy for minor cytologic abnormalities in adolescents should be discouraged because it can potentially result in harm through unnecessary treatment.Pregnant women are also considered a special population. The only indication for therapy of cervical neoplasia in pregnant women is invasive cancer. Therefore, it is reasonable to defer colposcopy in pregnant women at low risk for having cancer. Finally, it should be cautioned that endocervical curettage is contraindicated in pregnant patients.Atypical squamous cellsASC is subcategorized into atypical squamous cells of undetermined significance (ASC-US) and atypical squamous cells, cannot exclude HSIL (ASC-H). There are several factors that need to be taken into consideration when managing women with ASC. One is that a cytological result of ASC is the least reproducible of all cytologic categories.13Stoler M.H. Schiffman M. Interobserver reproducibility of cervical cytologic and histologic interpretations: realistic estimates from the ASCUS-LSIL Triage Study.JAMA. 2001; 285: 1500-1505Crossref PubMed Scopus (930) Google Scholar, 14Confortini M. Carozzi F. Dalla Palma P. et al.Interlaboratory reproducibility of atypical squamous cells of undetermined significance report: a national survey.Cytopathology. 2003; 14: 263-268Crossref PubMed Scopus (29) Google Scholar, 15Gatscha R.M. Abadi M. Babore S. Chhieng D. Miller M.J. Saigo P.E. Smears diagnosed as ASCUS: interobserver variation and follow-up.Diagn Cytopathol. 2001; 25: 138-140Crossref PubMed Scopus (28) Google Scholar Another is that the prevalence of invasive cancer is low in women with ASC (approximately 0.1-0.2%).16Jones B.A. Novis D.A. 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: 665-671PubMed Google Scholar Finally, it is important to note that the prevalence of CIN 2,3 is higher among women with ASC-H than women with ASC-US. Because of this, ASC-H should be considered to represent equivocal HSIL.Clinical data from ALTS and other studies1ASCUS-LSIL Triage Study (ALTS) GroupResults of a randomized trial on the management of cytology interpretations of atypical squamous cells of undetermined significance.Am J Obstet Gynecol. 2003; 188: 1383-1392PubMed Google Scholar, 17Manos M.M. Kinney W.K. Hurley L.B. et al.Identifying women with cervical neoplasia: using human papillomavirus DNA testing for equivocal Papanicolaou results.JAMA. 1999; 281: 1605-1610Crossref PubMed Scopus (554) Google Scholar, 18Lonky N.M. Felix J.C. Naidu Y.M. Wolde-Tsadik G. Triage of atypical squamous cells of undetermined significance with hybrid capture II: colposcopy and histologic human papillomavirus correlation.Obstet Gynecol. 2003; 101: 481-489Crossref PubMed Scopus (55) Google Scholar, 19Bergeron C. Jeannel D. Poveda J. Cassonnet P. Orth G. Human papillomavirus testing in women with mild cytologic atypia.Obstet Gynecol. 2000; 95: 821-827Crossref PubMed Scopus (102) Google Scholar have demonstrated that 2 repeat cytologic examinations performed at 6-month intervals, testing for HPV, and a single colposcopic examination are all safe and effective approaches to managing women with ASC-US. Therefore, the 2001 Consensus Guidelines recognized that all 3 approaches were acceptable for managing women with ASC-US. The scientific basis for the 2001 recommendation has been strengthened over the last 5 years by additional clinical studies, additional analyses of the ALTS data, and metaanalyses of published studies.18Lonky N.M. Felix J.C. Naidu Y.M. Wolde-Tsadik G. Triage of atypical squamous cells of undetermined significance with hybrid capture II: colposcopy and histologic human papillomavirus correlation.Obstet Gynecol. 2003; 101: 481-489Crossref PubMed Scopus (55) Google Scholar, 20Pretorius R.G. Peterson P. Novak S. Azizi F. Sadeghi M. Lorincz A.T. Comparison of two signal-amplification DNA tests for high-risk HPV as an aid to colposcopy.J Reprod Med. 2002; 47: 290-296PubMed Google Scholar, 21Guyot A. Karim S. Kyi M.S. Fox J. Evaluation of adjunctive HPV testing by Hybrid Capture II in women with minor cytological abnormalities for the diagnosis of CIN2/3 and cost comparison with colposcopy.BMC Infect Dis. 2003; 3: 23Crossref PubMed Scopus (24) Google Scholar, 22Dalla Palma P. Pojer A. Girlando S. HPV triage of women with atypical squamous cells of undetermined significance: a 3-year experience in an Italian organized programme.Cytopathology. 2005; 16: 22-26Crossref PubMed Scopus (19) Google Scholar, 23Cox J.T. Schiffman M. Solomon D. Prospective follow-up suggests similar risk of subsequent cervical intraepithelial neoplasia grade 2 or 3 among women with cervical intraepithelial neoplasia grade 1 or negative colposcopy and directed biopsy.Am J Obstet Gynecol. 2003; 188: 1406-1412Abstract Full Text Full Text PDF PubMed Scopus (320) Google Scholar, 24Guido R. Solomon D. Schiffman M. Burke L. Comparison of management strategies for women diagnosed as CIN 1 or less, postcolposcopic evaluation: data from the ASCUS and LSIL Triage Study (ALTS), a Multicenter randomized trial.J Low Genit Tract Dis. 2002; 6: 176Google Scholar, 25Arbyn M. Buntinx F. Van Ranst M. Paraskevaidis E. Martin-Hirsch P. Dillner J. Virologic versus cytologic triage of women with equivocal Pap smears: a meta-analysis of the accuracy to detect high-grade intraepithelial neoplasia.J Natl Cancer Inst. 2004; 96: 280-293Crossref PubMed Scopus (339) Google Scholar “Reflex” testing refers to testing either the original liquid-based cytology residual specimen or a separate sample cocollected at the time of the initial screening visit for HPV testing. This approach eliminates the need for women to return to the office or clinic for repeat testing, rapidly assures many women that they do not have a significant lesion, spares 40-60% of women from undergoing colposcopy, and has been shown to have a favorable cost-effectiveness ratio.26Kulasingam S.L. Kim J.J. Lawrence W.F. et al.Cost-effectiveness analysis based on the atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion Triage Study (ALTS).J Natl Cancer Inst. 2006; 98: 92-100Crossref PubMed Scopus (87) Google Scholar, 27Kim J.J. Wright T.C. Goldie S.J. Cost-effectiveness of alternative triage strategies for atypical squamous cells of undetermined significance.JAMA. 2002; 287: 2382-2390Crossref PubMed Scopus (258) Google ScholarBecause a single colposcopic examination can miss significant lesions, women who are referred for colposcopy and found not to have CIN 2,3 require additional follow-up. ALTS evaluated different postcolposcopy follow-up strategies and found that HPV testing performed 12 months after the initial colposcopy and 2 repeat cytology examinations performed at 6 month intervals performed similarly.28Guido R. Schiffman M. Solomon D. Burke L. Postcolposcopy management strategies for women referred with low-grade squamous intraepithelial lesions or human papillomavirus DNA-positive atypical squamous cells of undetermined significance: a two-year prospective study.Am J Obstet Gynecol. 2003; 188: 1401-1405Abstract Full Text Full Text PDF PubMed Scopus (175) Google Scholar Combining cytology with HPV testing did not increase sensitivity and reduced specificity.28Guido R. Schiffman M. Solomon D. Burke L. Postcolposcopy management strategies for women referred with low-grade squamous intraepithelial lesions or human papillomavirus DNA-positive atypical squamous cells of undetermined significance: a two-year prospective study.Am J Obstet Gynecol. 2003; 188: 1401-1405Abstract Full Text Full Text PDF PubMed Scopus (175) Google ScholarSpecial populationsThe prevalence of HPV DNA positivity changes with age among women with ASC-US. Rates of HPV DNA positivity are much higher in younger, compared with older, women with ASC-US.29Sherman M.E. Solomon D. Schiffman M. Qualification of ASCUS A comparison of equivocal LSIL and equivocal HSIL cervical cytology in the ASCUS LSIL Triage Study.Am J Clin Pathol. 2001; 116: 386-394Crossref PubMed Scopus (153) Google Scholar, 30Boardman L.A. Stanko C. Weitzen S. Sung C.J. Atypical squamous cells of undetermined significance: human papillomavirus testing in adolescents.Obstet Gynecol. 2005; 105: 741-746Crossref PubMed Scopus (37) Google Scholar Thus, using HPV testing to manage adolescents with ASC-US would refer large numbers of women at low risk for having cancer to colposcopy. ASC-US is less common in postmenopausal than premenopausal women, and the risk of significant pathology in postmenopausal women with a history of cervical cancer screening is relatively low.10Insinga R.P. Glass A.G. Rush B.B. Diagnoses and outcomes in cervical cancer screening: a population-based study.Am J Obstet Gynecol. 2004; 191: 105-113Abstract Full Text Full Text PDF PubMed Scopus (189) Google Scholar, 31Eltoum I.A. Chhieng D.C. Roberson J. McMillon D. Partridge E.E. Reflex human papilloma virus infection testing detects the same proportion of cervical intraepithelial neoplasia grade 2-3 in young versus elderly women.Cancer. 2005; 105: 194-198Crossref PubMed Scopus (23) Google Scholar, 32Sawaya G.F. Kerlikowske K. Lee N.C. Gildengorin G. Washington A.E. Frequency of cervical smear abnormalities within 3 years of normal cytology.Obstet Gynecol. 2000; 96: 219-223Crossref PubMed Scopus (80) Google Scholar HPV testing is actually more efficient in older, compared with younger, women with ASC-US because it refers a lower proportion to colposcopy.31Eltoum I.A. Chhieng D.C. Roberson J. McMillon D. Partridge E.E. Reflex human papilloma virus infection testing detects the same proportion of cervical intraepithelial neoplasia grade 2-3 in young versus elderly women.Cancer. 2005; 105: 194-198Crossref PubMed Scopus (23) Google Scholar, 33Sherman M.E. Schiffman M. Cox J.T. Group T.A. Effects of age and HPV load on colposcopic triage: data from the ASCUS LSIL Triage Study (ALTS).J Natl Cancer Inst. 2002; 94: 102-107Crossref PubMed Scopus (239) Google Scholar, 34Bruner K.S. Davey D.D. ASC-US and HPV testing in women aged 40 years and over.Diagn Cytopathol. 2004; 31: 358-361Crossref PubMed Scopus (15) Google ScholarASC-US is quite common in HIV-infected women.35Duerr A. Paramsothy P. Jamieson D.J. et al.Effect of HIV infection on atypical squamous cells of undetermined significance.Clin Infect Dis. 2006; 42: 855-861Crossref PubMed Scopus (32) Google Scholar, 36Massad L.S. Ahdieh L. Benning L. et al.Evolution of cervical abnormalities among women with HIV-1: evidence from surveillance cytology in the women’s interagency HIV study.J Acquir Immune Defic Syndr. 2001; 27: 432-442PubMed Google Scholar Previously, based on studies that had reported a high prevalence of both HPV DNA positivity and significant cervical pathology in this population,4Wright Jr, T.C. Cox J.T. Massad L.S. Twiggs L.B. Wilkinson E.J. 2001 consensus guidelines for the management of women with cervical cytological abnormalities.JAMA. 2002; 287: 2120-2129Crossref PubMed Scopus (1070) Google Scholar it was recommended that all immunosuppressed women with ASC-US undergo colposcopy. More recent studies have found a lower prevalence of CIN 2,3 and HPV DNA positivity; therefore, immunosuppressed women should be managed in the same manner as women in the general population.37Massad L.S. Schneider M.F. Watts D.H. et al.HPV testing for triage of HIV-infected women with Papanicolaou smears read as atypical squamous cells of uncertain significance.J Womens Health (Larchmt). 2004; 13: 147-153Crossref PubMed Scopus (19) Google Scholar, 38Kirby T.O. Allen M.E. Alvarez R.D. Hoesley C.J. Huh W.K. High-risk human papillomavirus and cervical intraepithelial neoplasia at time of atypical squamous cells of undetermined significance cytologic results in a population with human immunodeficiency virus.J Low Genit Tract Dis. 2004; 8: 298-303Crossref PubMed Scopus (22) Google Scholar The risk of cancer is relatively low among pregnant women with ASC-US, and some studies have found that antepartum colposcopic evaluation does not add to management.39Dunn T.S. Bajaj J.E. Stamm C.A. Beaty B. Management of the minimally abnormal Papanicolaou smear in pregnancy.J Low Genit Tract Dis. 2001; 5: 133-137PubMed Google ScholarRecommended Management of Women with ASC-USGeneral management approachesA program of DNA testing for high-risk (oncogenic) types of HPV, repeat cervical cytologic testing, or colposcopy are all acceptable methods for managing women over the age of 20 years with ASC-US. (AI) When liquid-based cytology is used or when cocollection for HPV DNA testing can be done, “reflex” HPV DNA testing is the preferred approach. (AI)Women with ASC-US who are HPV DNA negative can be followed up with repeat cytologic testing at 12 months. (BII) Women who are HPV DNA positive should be managed in the same fashion as women with LSIL and be referred for colposcopic evaluation. (AII) Endocervical sampling is preferred for women in whom no lesions are identified (BII) and those with an unsatisfactory colposcopy (AII) but is acceptable for women with a satisfactory colposcopy and a lesion identified in the transformation zone. (CII) Acceptable postcolposcopy management options of women with ASC-US who are HPV positive, but in whom CIN is not identified, are HPV DNA testing at 12 months or repeat cytological testing at 6 and 12 months. (BII) It is recommended that HPV DNA testing not be performed at intervals less than 12 months. (EIII)When a program of repeat cytologic testing is used for managing women with ASC-US, it is recommended that cytologic testing be performed at 6-month intervals until 2 consecutive “negative for intraepithelial lesion or malignancy” results are obtained. (AII) Colposcopy is recommended for women with ASC-US or greater cytologic abnormality on a repeat test. (AII) After 2 repeat “negative for intraepithelial lesion or malignancy” results are obtained, women can return to routine cytologic screening. (AII)When colposcopy is used to manage women with ASC-US, repeat cytologic testing at 12 months is recommended for women in whom CIN is not identified. (BIII) Women found to have CIN should be managed according to the 2006 Consensus Guidelines for the Management of Cervical Intraepithelial Neoplasia.Because of the potential for overtreatment, the routine use of diagnostic excisional procedures such as the loop electrosurgical excision procedure is unacceptable for women with an initial ASC-US in the absence of histologically diagnosed CIN 2,3. (EII)ASC-US in Special PopulationsAdolescent womenIn adolescents with ASC-US, follow-up with annual cytologic testing is recommended. (BII) At the 12-month follow-up, only adolescents with HSIL or greater on the repeat cytology should be referred to colposcopy. At the 24-month follow-up, those with an ASC-US or greater result should be referred to colposcopy. (AII) HPV DNA testing and colposcopy are unacceptable for adolescents with ASC-US. (EII) If HPV testing is inadvertently performed, the results should not influence management.Immunosuppressed and postmenopausal womenHIV-infected, other immunosuppressed women, and postmenopausal women with ASC-US should be managed in the same manner as women in the general population. (BII)Pregnant womenManagement options for pregnant women over the age of 20 years with ASC-US are identical to those described for nonpregnant women, with the exception that it is acceptable to defer colposcopy until at least 6 weeks postpartum. (CIII) Endocervical curettage is unacceptable in pregnant women. (EIII)Recommended Management of Women with ASC-HThe recommended management of women with ASC-H is referral for colposcopic evaluation. (AII) In women in whom CIN 2,3 is not identified, follow-up with HPV DNA testing at 12 months or cytological testing at 6 and 12 months is acceptable. (CIII) Referral to colposcopy is recommended for women who subsequently test positive for HPV DNA or who are found to have ASC-US or greater on their repeat cytologic tests. (BII) If the HPV DNA test is negative or if 2 consecutive repeat cytologic tests are negative for intraepithelial lesion or malignancy, return to routine cytologic screening is recommended. (AI)LSILOver the last decade, the rate of LSIL has increased in the United States and in 2003 the mean LSIL reporting rate was 2.9% for liquid-based specimens.40Davey D.D. Neal M.H. Wilbur D.C. Colgan T.J. Styer P.E. Mody D.R. Bethesda 2001 implementation and reporting rates: 2003 practices of participants in the College of American Pathologists Interlaboratory Comparison Prog