Cervical cytology: Evaluation of atypical squamous cells (ASC-US and ASC-H)
- Annekathryn Goodman, MD
Annekathryn Goodman, MD
- Obstetrics, Gynecology, Reproductive Biology
- Harvard Medical School
- Division of Gynecologic Oncology
- Massachusetts General Hospital
- MGH Global Disaster Response
- Warner K Huh, MD
Warner K Huh, MD
- Margaret Cameron Spain Chair in Obstetrics/Gynecology
- Professor, Division of Gynecologic Oncology
- Senior Scientist, UAB Comprehensive Cancer Center
Cervical cytology became the standard screening test for cancer of the uterine cervix and premalignant cervical lesions with the introduction of the Papanicolaou (Pap) smear in 1941 . The addition of human papillomavirus testing to cervical cancer screening strategies has improved detection of cervical neoplasia and allowed further risk stratification.
Current terminology for reporting cervical cytology results includes the category atypical squamous cells (ASC), which differ from normal cells but do not meet criteria for a premalignant disease (squamous intraepithelial neoplasia [SIL]). ASC can be categorized as ASC-US, "of undetermined significance", or ASC-H, in which a high-grade squamous intraepithelial lesion (HSIL) cannot be excluded . A finding of ASC-H is associated with a markedly higher risk of premalignant disease or cervical cancer than ASC-US. (See 'Risk of premalignant or malignant disease' below.)
Evaluation of women with cervical cytology with atypical squamous cells is reviewed here. Cervical cancer screening strategies and techniques, interpretation of cervical cytology results, follow-up of other abnormal cytology results, and management of cervical neoplasia are discussed separately. (See "Screening for cervical cancer" and "Cervical cancer screening tests: Techniques for cervical cytology and human papillomavirus testing" and "Cervical and vaginal cytology: Interpretation of results (Pap test report)" and "Cervical cytology: Evaluation of low-grade squamous intraepithelial lesions (LSIL)" and "Cervical cytology: Evaluation of high-grade squamous intraepithelial lesions (HSIL)" and "Cervical cytology: Evaluation of atypical and malignant glandular cells" and "Cervical intraepithelial neoplasia: Management of low-grade and high-grade lesions".)
Terminology used to describe cervical cancer screening tests or cervical cytology results discussed here includes:
●Atypical squamous cells of undetermined significance (ASC-US) – Cells that display abnormalities more marked than simple reactive changes but do not display a squamous intraepithelial lesion (SIL).
- Papanicolaou GN, Traut HF. The diagnostic value of vaginal smears in carcinoma of the uterus. Am J Obstet Gynecol 1941; 42:193.
- Solomon D, Davey D, Kurman R, et al. The 2001 Bethesda System: terminology for reporting results of cervical cytology. JAMA 2002; 287:2114.
- Waxman AG, Chelmow D, Darragh TM, et al. Revised terminology for cervical histopathology and its implications for management of high-grade squamous intraepithelial lesions of the cervix. Obstet Gynecol 2012; 120:1465.
- Darragh TM, Colgan TJ, Thomas Cox J, et al. 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. Int J Gynecol Pathol 2013; 32:76.
- Massad LS, Einstein MH, Huh WK, et al. 2012 updated consensus guidelines for the management of abnormal cervical cancer screening tests and cancer precursors. J Low Genit Tract Dis 2013; 17:S1.
- Katki HA, Schiffman M, Castle PE, et al. Benchmarking CIN 3+ risk as the basis for incorporating HPV and Pap cotesting into cervical screening and management guidelines. J Low Genit Tract Dis 2013; 17:S28.
- ASCUS-LSIL Traige 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.
- Katki HA, Schiffman M, Castle PE, et al. Five-year risks of CIN 3+ and cervical cancer among women with HPV testing of ASC-US Pap results. J Low Genit Tract Dis 2013; 17:S36.
- Demirtas GS, Akman L, Demirtas O, et al. Clinical significance of ASCUS and ASC-H cytological abnormalities: a six-year experience at a single center. Eur J Gynaecol Oncol 2015; 36:150.
- Katki HA, Schiffman M, Castle PE, 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.
- Committee on Practice Bulletins—Gynecology. Practice Bulletin No. 168: Cervical Cancer Screening and Prevention. Obstet Gynecol 2016; 128:e111.
- http://www.asccp.org/ (Accessed on March 22, 2012).
- Kim JJ, Wright TC, Goldie SJ. Cost-effectiveness of alternative triage strategies for atypical squamous cells of undetermined significance. JAMA 2002; 287:2382.
- Kulasingam SL, Kim JJ, Lawrence WF, 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.
- Stout NK, Goldhaber-Fiebert JD, Ortendahl JD, Goldie SJ. Trade-offs in cervical cancer prevention: balancing benefits and risks. Arch Intern Med 2008; 168:1881.
- Arbyn M, Buntinx F, Van Ranst M, et al. 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.
- Arbyn M, Paraskevaidis E, Martin-Hirsch P, et al. Clinical utility of HPV-DNA detection: triage of minor cervical lesions, follow-up of women treated for high-grade CIN: an update of pooled evidence. Gynecol Oncol 2005; 99:S7.
- Arbyn M, Roelens J, Simoens C, et al. Human papillomavirus testing versus repeat cytology for triage of minor cytological cervical lesions. Cochrane Database Syst Rev 2013; :CD008054.
- Legood R, Gray A, Wolstenholme J, Moss S. Lifetime effects, costs, and cost effectiveness of testing for human papillomavirus to manage low grade cytological abnormalities: results of the NHS pilot studies. BMJ 2006; 332:79.
- Eltoum IA, Chhieng DC, Roberson J, et al. 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.
- Sherman ME, Schiffman M, Cox JT, Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesion Triage Study Group. Effects of age and human papilloma viral load on colposcopy triage: data from the randomized Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesion Triage Study (ALTS). J Natl Cancer Inst 2002; 94:102.
- O'Connor NR, Kumar P. Conservative management of end-stage renal disease without dialysis: a systematic review. J Palliat Med 2012; 15:228.
- Katki HA, Schiffman M, Castle PE, 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.
- Slawson DC, Bennett JH, Herman JM. Follow-up Papanicolaou smear for cervical atypia: are we missing significant disease? A HARNET Study. J Fam Pract 1993; 36:289.
- Castle PE, Fetterman B, Thomas Cox J, et al. The age-specific relationships of abnormal cytology and human papillomavirus DNA results to the risk of cervical precancer and cancer. Obstet Gynecol 2010; 116:76.
- Katki HA, Schiffman M, Castle PE, 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.
- Kjær SK, Frederiksen K, Munk C, Iftner T. Long-term absolute risk of cervical intraepithelial neoplasia grade 3 or worse following human papillomavirus infection: role of persistence. J Natl Cancer Inst 2010; 102:1478.
- Benard VB, Watson M, Castle PE, Saraiya M. Cervical carcinoma rates among young females in the United States. Obstet Gynecol 2012; 120:1117.
- Winer RL, Lee SK, Hughes JP, et al. Genital human papillomavirus infection: incidence and risk factors in a cohort of female university students. Am J Epidemiol 2003; 157:218.
- Moscicki AB, Hills N, Shiboski S, et al. Risks for incident human papillomavirus infection and low-grade squamous intraepithelial lesion development in young females. JAMA 2001; 285:2995.
- McAllum B, Sykes PH, Sadler L, et al. Is the treatment of CIN 2 always necessary in women under 25 years old? Am J Obstet Gynecol 2011; 205:478.e1.
- Castle PE, Schiffman M, Wheeler CM, Solomon D. Evidence for frequent regression of cervical intraepithelial neoplasia-grade 2. Obstet Gynecol 2009; 113:18.
- Moscicki AB, Schiffman M, Burchell A, et al. Updating the natural history of human papillomavirus and anogenital cancers. Vaccine 2012; 30 Suppl 5:F24.
- Rodríguez AC, Schiffman M, Herrero R, et al. Longitudinal study of human papillomavirus persistence and cervical intraepithelial neoplasia grade 2/3: critical role of duration of infection. J Natl Cancer Inst 2010; 102:315.
- Katki HA, Schiffman M, Castle PE, 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.
- Moscicki AB, Ma Y, Wibbelsman C, et al. Rate of and risks for regression of cervical intraepithelial neoplasia 2 in adolescents and young women. Obstet Gynecol 2010; 116:1373.
- Matsumoto K, Oki A, Furuta R, et al. Predicting the progression of cervical precursor lesions by human papillomavirus genotyping: a prospective cohort study. Int J Cancer 2011; 128:2898.
- Herbert A, Holdsworth G, Kubba A. Why young women should be screened for cervical cancer: the distinction between CIN2 and CIN3. Int J Cancer 2010; 126:2256.
- Michael CW, Esfahani FM. Pregnancy-related changes: a retrospective review of 278 cervical smears. Diagn Cytopathol 1997; 17:99.
- Pisharodi LR, Jovanoska S. Spectrum of cytologic changes in pregnancy. A review of 100 abnormal cervicovaginal smears, with emphasis on diagnostic pitfalls. Acta Cytol 1995; 39:905.
- Onuma K, Saad RS, Kanbour-Shakir A, et al. Clinical implications of the diagnosis "atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion" in pregnant women. Cancer 2006; 108:282.
- Clement PB, Young RH. Endometrioid carcinoma of the uterine corpus: a review of its pathology with emphasis on recent advances and problematic aspects. Adv Anat Pathol 2002; 9:145.
- Tokmak A, Guzel AI, Ozgu E, et al. Clinical significance of atypical squamous cells of undetermined significance in detecting preinvasive cervical lesions in post- menopausal Turkish women. Asian Pac J Cancer Prev 2014; 15:6639.
- RISK OF PREMALIGNANT OR MALIGNANT DISEASE
- RATIONALE FOR EVALUATION STRATEGIES
- EVALUATION OF ASC-US
- Women ages 25 or older
- - HPV triage vs. repeat cytology
- Persistent HPV-positive ASC-US
- Persistent HPV-negative ASC-US
- Women ages 21 to 24
- EVALUATION OF ASC-H
- Women ages 25 and older
- Women ages 21 to 24
- SPECIAL POPULATIONS
- Pregnant women
- Postmenopausal women
- Adolescents inadvertently screened
- Immunocompromised women
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS