title: 2012 updated consensus guidelines for the management of abnormal cervical cancer screening tests and cancer precursors.
abstract: A group of 47 experts representing 23 professional societies, national and international health organizations, and federal agencies met in Bethesda, MD, September 14-15, 2012, to revise the 2006 American Society for Colposcopy and Cervical Pathology Consensus Guidelines. The group's goal was to provide revised evidence-based consensus guidelines for managing women with abnormal cervical cancer screening tests, cervical intraepithelial neoplasia (CIN) and adenocarcinoma in situ (AIS) following adoption of cervical cancer screening guidelines incorporating longer screening intervals and co-testing. In addition to literature review, data from almost 1.4 million women in the Kaiser Permanente Northern California Medical Care Plan provided evidence on risk after abnormal tests. Where data were available, guidelines prescribed similar management for women with similar risks for CIN 3, AIS, and cancer. Most prior guidelines were reaffirmed. Examples of updates include: Human papillomavirus-negative atypical squamous cells of undetermined significance results are followed with co-testing at 3 years before return to routine screening and are not sufficient for exiting women from screening at age 65 years; women aged 21-24 years need less invasive management, especially for minor abnormalities; postcolposcopy management strategies incorporate co-testing; endocervical sampling reported as CIN 1 should be managed as CIN 1; unsatisfactory cytology should be repeated in most circumstances, even when HPV results from co-testing are known, while most cases of negative cytology with absent or insufficient endocervical cells or transformation zone component can be managed without intensive follow-up.
authors: Washington University School of Medicine, St. Louis, Missouri; Albert Einstein College of Medicine, New York, New York; University of Alabama School of Medicine, Birmingham, Alabama; Division of Cancer Epidemiology and Genetics and Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland; The Permanente Medical Group, Sacramento, California; and Emory University School of Medicine, Atlanta, Georgia.
authors: L Stewart
authors: LS
authors: Massad
authors: Mark H
authors: MH
authors: Einstein
authors: Warner K
authors: WK
authors: Huh
authors: Hormuzd A
authors: HA
authors: Katki
authors: Walter K
authors: WK
authors: Kinney
authors: Mark
authors: M
authors: Schiffman
authors: Diane
authors: D
authors: Solomon
authors: Nicolas
authors: N
authors: Wentzensen
authors: Herschel W
authors: HW
authors: Lawson
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology* / Q000628:therapy; D000328:Adult; D000368:Aged; D002278:Carcinoma in Situ / Q000473:pathology* / Q000628:therapy; D055088:Early Detection of Cancer / Q000592:standards*; D005260:Female; D006801:Humans; D008875:Middle Aged; D002583:Uterine Cervical Neoplasms / Q000473:pathology* / Q000628:therapy; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000473:pathology* / Q000628:therapy
references: Solomon D, Davey D, Kurman R, Moriarty A, O’Connor D, Prey M, et al.. The 2001 Bethesda System: terminology for reporting results of cervical cytology. JAMA 2002;287:2114–9.
references: ASC-US-LSIL Triage Study (ALTS) Group. Results of a randomized trial on the management of cytology interpretations of atypical squamous cells of undetermined significance. Am J Obstet Gynecol 2003;188:1383–92.
references: ASC-US-LSIL Triage Study (ALTS) Group. A randomized trial on the management of low-grade squamous intraepithelial lesion cytology interpretations. Am J Obstet Gynecol 2003;188:1393–400.
references: Wright TC, Cox JT, Massad LS, Twiggs LB, Wilkinston EJ. 2001 Consensus guidelines for the management of women with cervical cytological abnormalities and cervical cancer precursors: Part 1: Cytological abnormalities. JAMA 2002;287:2120–9.
references: Wright TC Jr, Cox JT, Massad LS, Carlson J, Twiggs LB, Wilkinson EJ; 2001 ASCCP-sponsored Consensus Workshop. 2001 consensus guidelines for the management of women with cervical intraepithelial neoplasia. J Low Genit Tract Dis 2003;7:154–67.
references: Wright TC Jr, Massad LS, Dunton CJ, Spitzer M, Wilkinson EJ, Solomon D; 2006 ASCCP-Sponsored Consensus Conference. 2006 consensus guidelines for the management of women with abnormal cervical screening tests. J Low Genit Tract Dis 2007;11:201–22.
references: Davey DD, Austin RM, Birdsong G, Buck HW, Cox JT, Darragh TM, et al.. ASCCP patient management guidelines: Pap test specimen adequacy and quality indicators. J Low Genit Tract Dis 2002;6:195–9.
references: Davey DD, Cox JT, Austin RM, Birdsong G, Colgan TJ, Howell LP, et al.. Cervical cytology specimen adequacy: Updated patient management guidelines. J Low Genit Tract Dis 2008;12:71–81.
references: Saslow D, Solomon D, Lawson HW, Killackey M, Kulasingam SL, Cain J, et al.. American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology screening guidelines for the prevention and early detection of cervical cancer. CA Cancer J Clin 2012;62:147–72.
references: Moyer VA, LeFevre ML, Siu AL, Bibbins-Domingo K, Curry SJ, Flores G, et al. for the U.S. Preventive Services Task Force. Screening for cervical cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2012;156:880–91.
references: Castle PE, Sideri M, Jeronimo J, Solomon D, Schiffman M. Risk assessment to guide the prevention of cervical cancer. J Low Genit Tract Dis 2008;12:1–7
references: Darragh TM, Colgan TJ, Cox JT, Heller DS, Henry MR, Luff RD, et al.; Members of LAST Project Work Groups. The Lower Anogenital Squamous Terminology Standardization Project for HPV-associated lesions: background and consensus recommendations from the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology. J Low Genit Tract Dis 2012;16:205–42.
references: Mogensen ST, Bak M, Dueholm M, Frost L, Knolblaugh NO, Praest J, et al.. Cytobrush and endocervical curettage in the diagnosis of dysplasia and malignancy of the uterine cervix. Acta Obstet Gynecol Scand 1997;76:69–73.
references: Goksedef BP, Api M, Kaya O, Gorgen H, Tarlaci A, Cetin A. Diagnostic accuracy of two endocervical sampling method: randomized controlled trial. Arch Gynecol Obstet 2013;287:117–22.
references: Kyrgiou M, Tsoumpou I, Vrekoussis T, Martin-Hirsch P, Arbyn M, Prendiville W, et al.. The up-to-date evidence on colposcopy practice and treatment of cervical intraepithelial neoplasia: the Cochrane colposcopy and cervical cytopathology collaborative group (C5 group) approach. Cancer Treat Rev 2006;32:516–23.
references: Nuovo J, Melnikow J, Willan AR, Chan BK. Treatment outcomes for squamous intraepithelial lesions. Int J Gynaecol Obstet 2000;68:25–33.
references: Kalliala I, Nieminen P, Dyba T, Pukkala E, Anttilla A. Cancer free survival after CIN treatment: comparisons of treatment methods and histology. Gynecol Oncol 2007;105:228–33.
references: Paraskevaidis E, Arbyn M, Sotiriadis A, Diakomanolis E, Martin-Hirsch P, Koliopoulos G, et al.. The role of HPV DNA testing in the follow-up period after treatment for CIN: a systematic review of the literature. Cancer Treat Rev 2004;30:205–11.
references: Jakobsson M, Gissler M, Paavonen J, Tapper AM. Long-term mortality in women treated for cervical intraepithelial neoplasia. BJOG 2009;116:838–44.
references: Kalogirou D, Antoniou G, Karakitsos P, Potsis D, Kalogirou O, Giannikos L. Predictive factors used to justify hysterectomy after loop conization: increasing age and severity of disease. Eur J Gynaecol Oncol 1997;18:113–6.
references: Ghaem-Maghami S, Sagi S, Majeed G, Soutter WP. Incomplete excision of cervical intraepithelial neoplasia and risk of treatment failure: a meta-analysis. Lancet Oncol 2007;8:985–93.
references: Kocken M, Uijterwaal MH, de Vries AL, Berkhof J, Ket JC, Helmerhorst TJ, et al.. High-risk human papillomavirus testing versus cytology in predicting post-treatment disease in women treated for high-grade cervical disease: a systematic review and meta-analysis. Gynecol Oncol 2012;125:500–7.
references: Katki HA, Schiffman M, Castle PE, Fetterman B, Poitras NE, Lorey T, et al.. Five-year risk of CIN 3+ and cervical cancer among women with HPV testing of ASC-US Pap results. J Low Genit Tract Dis 2013;17:S36–42.
references: Jakobsson M, Gissler M, Paavonen J, Tapper AM. Loop electrosurgical excision procedure and the risk for preterm birth. Obstet Gynecol 2009;114:504–10.
references: Sadler L, Saftlas A, Wang W, Exeter M, Whittaker J, McCowan L. Treatment for cervical intraepithelial neoplasia and risk of preterm delivery. JAMA 2004;29:2100–6.
references: Bruinsma FJ, Quinn MA. The risk of preterm birth following treatment for precancerous changes in the cervix: a systematic review and meta-analysis. BJOG 2011;118:1031–41.
references: Moscicki AB, Ma Y, Wibblesman C, Darragh TM, Powers A, Farhat S, et al.. Rate of and risks for regression of cervical intraepithelial neoplasia 2 in adolescents and young women. Obstet Gynecol 2010;116:1373–80.
references: Moscicki AB, Shiboski S, Hills NK, Powell KJ, Jay N, Hanson EN, et al.. Regression of low-grade squamous intra-epithelial lesions in young women. Lancet 2004;364:1678–83.
references: Katki HA, Schiffman M, Castle PE, Fetterman B, Poitras NE, Lorey T, et al.. Five-year risk of CIN 3+ to guide the management of women aged 21 to 24 years. J Low Genit Tract Dis 2013;17:S64–8.
references: Moscicki AB, Cox JT. Practice improvement in cervical screening and management (PICSM): symposium on management of cervical abnormalities in adolescents and young women. J Low Genit Tract Dis 2010;14:73–80.
references: Benard VB, Watson M, Castle PE, Saraiya M. Cervical Cancer Rates Among Young Females in the United States. Obstet Gynecol 2012;120:1117–23.
references: Winer RL, Lee SK, Hughes JP, Adam DE, Kiviat NB, Koutsky LA. Genital human papillomavirus infection: incidence and risk factors in a cohort of female university students. Am J Epidemiol 2003;157:218–26.
references: Moscicki AB, Hills N, Shiboski S, Powell K, Jay N, Hanson E, et al.. Risks for incident human papillomavirus infection and low-grade squamous intraepithelial lesion development in young females. JAMA 2001;285:2995–3002.
references: Kahn J, Slap G, Bernstein D, Kollar L, Tissot A, Hillard P, et al.. Psychological, behavioral, and interpersonal impact of human papillomavirus and Pap test results. J Womens Health 2005;14:650–9.
references: Kahn J, Slap G, Bernstein D, Tissot A, Kollar L, Hillard P, et al.. Personal Meaning of Human Papillomavirus and Pap Test Results in Adolescent and Young Adult Women. Health Psychol 2007;26:192–200.
references: Lerner D, Parsons SK, Justicia-Linde F, Chelmow D, Chang H, Rogers WH, et al.. The impact of pre-cancerous cervical lesions on functioning at work and work productivity. J Occup Environ Med 2010;52:926–33.
references: Moriarty AT, Clayton AC, Zaleski S, Henry MR, Schwartz MR, Eversole GM, et al.. Unsatisfactory reporting rates: 2006 practices of participants in the College of American Pathologists interlaboratory comparison program in gynecologic cytology. Arch Pathol Lab Med 2009;133:1912–6.
references: Ransdell JS, Davey DD, Zaleski S. Clinicopathologic correlation of the unsatisfactory Papanicolaou smear. Cancer (Cancer Cytopathol) 1997;81:139–43.
references: Siebers AG, Klinkhamer PJJM, Vedder JEM, Arbyn M, Bulten J. Causes and relevance of unsatisfactory and satisfactory but limited smears of liquid-based compared with conventional cervical cytology. Arch Pathol Lab Med 2012;136:76–83
references: Zhao C, Austin RM. High-risk human papillomavirus DNA test results are useful for disease risk stratification in women with unsatisfactory liquid-based cytology Pap test results. J Lower Genit Tract Dis 2009;13:79–84.
references: Holton T, Smith D, Terry M, Madgwick A, Levine T. The effect of lubricant contamination on ThinPrep liquid-based preparations. Cytopathology 2008;19:236–43.
references: Buntinx F, Brouwers M. Relation between sampling device and detection of abnormality in cervical smears: a meta-analysis of randomized and quasi-randomised studies. BMJ 1996;313:1285–90.
references: Huang A, Quinn M, Tan J. Outcome in women with no endocervical component on cervical cytology after treatment for high-grade cervical dysplasia. Aust N Z J Obstet Gynaec 2009;49:426–8.
references: Mitchell H, Hocking J, Saville M. Cervical cytology screening history of women diagnosed with adenocarcinoma in situ of the cervix. A case-control study. Acta Cytol 2004;48:595–600
references: Mitchell HS. Longitudinal analysis of histologic high-grade disease after negative cervical cytology according to endocervical status. Cancer 2001;93:237–40
references: Elumir-Tanner L, Doraty M. Management of Papanicolaou test results that lack endocervical cells. CMAJ 2011;183:563–8.
references: Zhao C, Austin RM. Human papillomavirus DNA detection in ThinPrep Pap test vials is independent of cytologic sampling of the transformation zone. Gynecol Oncol 2007;107:231–5.
references: Huang A, Quinn M, Tan J. Outcome in women with no endocervical component on cervical cytology after treatment for high-grade cervical dysplasia. Aust NZ J Obstet Gynaecol 2009;49:426–8.
references: Katki HA, Schiffman M, Castle PE, Fetterman B, Poitras NE, Lorey T, et al.. Five-year risks of CIN 3+ and cervical cancer among women who test Pap-negative but are HPV-positive. J Low Genit Tract Dis 2013;17:S56–63.
references: Rodriguez AC, Schiffman M, Herrero R, Wacholder S, Hildesheim A, Castle PE, et al. for the Proyecto Epidemiológico Guanacaste Group. Rapid clearance of human papillomavirus and implications for clinical focus on persistent infections. J Natl Cancer Inst 2008;100:513–7.
references: Stoler MH, Wright TC, Sharma A, Apple R, Gutekunst K, Wright TL. High-risk human papillomavirus testing in women with ASC-US cytology: results from the ATHENA HPV study. Am J Clin Pathol 2011;135:466–75.
references: Einstein MH, Martens MG, Garcia FA, Ferris DG, Mitchell AL, Day SP, et al.. Clinical validation of the Cervista HPV HR and 16/18 genotyping tests for use in women with ASC-US cytology. Gynecol Oncol 2010;118:116–22.
references: Gage JC, Schiffman M, Solomon D, Wheeler CM, Castle PE. Comparison of measurements of human papillomavirus persistence for postcolposcopic surveillance for cervical precancerous lesions. Cancer Epidemiol Biomarkers Prev 2010;19:1668–74.
references: Cox JT, 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;188:1406–12.
references: Moore G, Fetterman B, Cox JT, Poitras N, Lorey T, Kinney W, et al.. Lessons from practice: risk of CIN3 or cancer associated with an LSIL or HPV-positive ASC-US screening result in women aged 21-24. J Lower Genit Tract Dis 2010;14:97–102.
references: Arbyn M, Sasieni P, Meijer CJ, Clavel C, Koliopoulos G, Dillner J. Chapter 9: clinical applications of HPV testing: a summary of meta-analyses. Vaccine 2006;24 (suppl 3):S78–S89.
references: Katki HA, Schiffman M, Castle PE, Fetterman B, Poitras NE, Lorey T, et al.. Five-year risks of CIN 2+ and CIN 3+ among women with HPV-positive and HPV-negative LSIL Pap results. J Low Genit Tract Dis 2013;17:S43–9.
references: Katki HA, Gage JC, Schiffman M, Castle PE, Fetterman B, Poitras NE, et al.. Follow-up testing after colposcopy: five-year risk of CIN 2+ after a colposcopic diagnosis of CIN 1 or less. J Low Genit Tract Dis 2013;17:S69–77.
references: Massad LS, Collins YC, Meyer PM. Biopsy correlates of abnormal cervical cytology classified using the Bethesda system. Gynecol Oncol 2001;82:516–22.
references: Alvarez RD, Wright TC. Effective cervical neoplasia detection with a novel optical detection system: a randomized trial. Gynecol Oncol 2007;104:281–9.
references: Dunn TS, Burke M, Shwayder J. A “see and treat” management for high grade squamous intraepithelial lesion Pap smears. J Lower Gen Tract Dis 2003;7:104–6.
references: Katki HA, Schiffman M, Castle PE, Fetterman B, Poitras NE, Lorey T, et al.. Five-year risk of cervical cancer and CIN3 for HPV-positive and HPV-negative high-grade Pap results. J Low Genit Tract Dis 2013;17:S50–5.
references: Pretorius RG, Zhange WH, Belinson JL, Huang MN, Wu LY, Zhange X, et al.. Colposcopically directed biopsy, random cervical biopsy, and endocervical curettage in the diagnosis of Cervical intraepithelial neoplasia II or worse. Am J Obstet Gynecol 2004;191:430–4.
references: Gage JC, Hanson VW, Abbey K, Dipery S, Gardner S, Kubota J, et al.. Number of cervical biopsies and sensitivity of colposcopy. Obstet Gynecol 2006;108:264–72.
references: Guido R, Schiffman M, Solomon D; Burke L for the ASCUS/LSIL Triage Study (ALTS) Group. Post-colposcopy management strategies for women referred with low-grade squamous intraepithelial lesions of human papillomavirus DNA-positive atypical squamous cells of undetermined significance: a two-year prospective trial. Am J Obstet Gynecol 2003;188:1401–5.
references: Lee KR, Darragh TM, Joste NE, Krane JF, Sherman ME, Hurley LB, et al.. Atypical glandular cells of undetermined significance (AGUS): interobserver reproducibility in cervical smears and corresponding thin-layer preparations. Am J Clin Pathol 2002;117:96–102.
references: Davey DD, Neal MH, Wilbur DC, Colgan TJ, Styer PE, Mody DR. Bethesda 2001 implementation and reporting rates: 2003 practices of participants in the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology. Arch Pathol Lab Med 2004;128:1224–9.
references: Zhao C, Florea A, Onisko A, Austin RM. Histologic follow-up results in 662 patients with Pap test findings of atypical glandular cells: results from a large academic womens hospital laboratory employing sensitive screening methods. Gynecol Oncol 2009;114:383–9.
references: Sharpless KE, Schnatz PF, Mandavilli S, Greene JF, Sorosky JI. Dysplasia associated with atypical glandular cells on cervical cytology. Obstet Gynecol 2005;105:494–500.
references: Castle PE, Fetterman M, Poitras N, Lorey T, Shaber R, Kinney W. Relationship of atypical glandular cell cytology, age and human papillomavirus detection to cervical and endometrial cancer risks. Obstet Gynecol 2010;115:243–8.
references: Simsir A, Carter W, Elgert P, Cangiarella J. Reporting endometrial cells in women 70 years and older: assessing the clinical usefulness of Bethesda 2001. Am J Clin Pathol 2005;123:571–5.
references: Schlecht NF, Platt RW, Duarte-Franco E, Costa MC, Sobrinho JP, Prado JC, et al.. Human papillomavirus infection and time to progression and regression of cervical intraepithelial neoplasia. J Natl Cancer Inst 2003;95:1336–43.
references: Sideri M, Iqidbashian S, Boveri S, Radice D, Casadio C, Spolti N, et al.. Age distribution of HPV genotypes in cervical intraepithelial neoplasia. Gynecol Oncol 2011;212:510–3.
references: Trimble CL, Piantadosi S, Gravitt P, Ronnett B, Pizer E, Elko A, et al.. Spontaneous regression of high-grade cervical dysplasia: effects of human papillomavirus type and HLA phenotype. Clin Cancer Res 2005;11:4717–23.
references: Petersen S, Belnap C, Larsen WI, Farley J. Grading of squamous dysplasia in endocervical curettage specimens: The case for conservative management of mild endocervical dysplasia. J Reprod Med 2007;52:917–21.
references: Ostor AG. Natural history of cervical intraepithelial neoplasia: A critical review. Intern J Gynecol Pathol 1993;12:186–92.
references: Holowaty P, Miller AB, Rohan T, To T. Natural history of dysplasia of the uterine cervix. J Natl Cancer Inst 1999;91:252–8.
references: Katki HA, Schiffman M, Castle PE, Fetterman B, Poitras NE, Lorey T, et al.. Five-year risk of recurrence after treatment of CIN 2, CIN 3, or AIS: performance of HPV and Pap cotesting in posttreatment management. J Low Genit Tract Dis 2013;17:S78–84.
references: Sherman ME, Wang SS, Carreon J, Devesa SS. Mortality trends for cervical squamous and adenocarcinoma in the United States. Relation to incidence and survival. Cancer 2005;103:1258–64.
references: Bull-Phelps SL, Garner EI, Walsh CS, Gehrig PA, Miller DS, Schorge JO. Fertility-sparing surgery in 101 women with adenocarcinoma in situ of the cervix. Gynecol Oncol 2007;107:316–9.
references: Costa S, Venturoli S, Negri G, Sideri M, Preti M, Pesaresi M, et al.. Factors predicting the outcome of conservatively treated adenocarcinoma in situ of the uterine cervix: an analysis of 166 cases. Gynecol Oncol 2012;124:490–5.
references: van Hanegem N, Barroilhet LM, Nucci MR, Bernstein M, Feldman S. Fertility-sparing treatment in younger women with adenocarcinoma in situ of the cervix. Gynecol Oncol 2012;124:72–7.
references: Lea JS, Shin CH, Sheets EE, Coleman RL, Gehrig PA, Duska LR, et al.. Endocervical curettage at conization to predict residual cervical adenocarcinoma in situ. Gynecol Oncol 2002;87:129–32.