Objective: To evaluate the role of human papillomavirus (HPV) genotyping in predicting the risk of cervical precancerous lesions or cancer in women with minor abnormal cytology. Methods and Materials: This study was conducted on 329 women with atypical squamous cells of undetermined significance (ASC-US) and 77 women with low-grade squamous intraepithelial lesions (LSIL) out of a total of 4,215 participants in a multicenter, cross-sectional study. Liquid-based cytology and the Hybrid Capture 2 test (HC2) were used to screen eligible women, and a Linear Array HPV genotyping test was performed on women with positive HC2 results. Results: The sensitivity and specificity for detecting cervical intraepithelial neoplasia grade 2 or worse (CIN2+) based on HPV 16/18 were 82% [95% confidence interval (CI): 52-95%] and 91% (95% CI: 87-94%) in women with ASC-US and 67% (95% CI: 35-88%) and 84% (95% CI: 73-91%) in women with LSIL. The women infected with HPV 16/18 had a significantly higher risk of developing CIN2+ than those infected with other high-risk HPV types in both the ASC-US (OR 9.93, 95% CI: 2.02-48.88) and LSIL (OR 7.45, 95% CI: 1.60-34.68) arms. Conclusions: Genotyping for HPV 16/18 greatly improves specificity, but at the expense of potential sensitivity in the triage of minor cytology abnormalities. The role of genotyping for HPV 16/18 in order to triage women with minor abnormal cytology should be further evaluated in future studies.

1.
Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F: Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2015;136:E359-E386.
2.
Nobbenhuis MA, Walboomers JM, Helmerhorst TJ, Rozendaal L, Remmink AJ, Risse EK, van der Linden HC, Voorhorst FJ, Kenemans P, Meijer CJ: Relation of human papillomavirus status to cervical lesions and consequences for cervical-cancer screening: a prospective study. Lancet 1999;354:20-25.
3.
Schlecht NF, Kulaga S, Robitaille J, Ferreira S, Santos M, Miyamura RA, Duarte-Franco E, Rohan TE, Ferenczy A, Villa LL, et al: Persistent human papillomavirus infection as a predictor of cervical intraepithelial neoplasia. JAMA 2001;286:3106-3114.
4.
Cervix cancer screening, vol 10; in: Handbooks on Cancer Prevention. Lyon, IARC Press, 2005.
5.
Mayrand MH, Duarte-Franco E, Rodrigues I, Walter SD, Hanley J, Ferenczy A, Ratnam S, Coutlee F, Franco EL; Canadian Cervical Cancer Screening Trial Study Group: Human papillomavirus DNA versus Papanicolaou screening tests for cervical cancer. N Engl J Med 2007;357:1579-1588.
6.
Naucler P, Ryd W, Tornberg S, Strand A, Wadell G, Elfgren K, Radberg T, Strander B, Johansson B, Forslund O, et al: Human papillomavirus and Papanicolaou tests to screen for cervical cancer. N Engl J Med 2007;357:1589-1597.
7.
Rijkaart DC, Berkhof J, Rozendaal L, van Kemenade FJ, Bulkmans NW, Heideman DA, Kenter GG, Cuzick J, Snijders PJ, Meijer CJ: Human papillomavirus testing for the detection of high-grade cervical intraepithelial neoplasia and cancer: final results of the POBASCAM randomised controlled trial. Lancet Oncol 2012;13:78-88.
8.
Pan QJ, Hu SY, Zhang X, Ci PW, Zhang WH, Guo HQ, Cao J, Zhao FH, Lytwyn A, Qiao YL: Pooled analysis of the performance of liquid-based cytology in population-based cervical cancer screening studies in China. Cancer Cytopathol 2013;121:473-482.
9.
Pan QJ, Hu SY, Guo HQ, Zhang WH, Zhang X, Chen W, Cao J, Jiang Y, Zhao FH, Qiao YL: Liquid-based cytology and human papillomavirus testing: a pooled analysis using the data from 13 population-based cervical cancer screening studies from China. Gynecol Oncol 2014;133:172-179.
10.
Arbyn M, Martin-Hirsch P, Buntinx F, Van Ranst M, Paraskevaidis E, Dillner J: Triage of women with equivocal or low-grade cervical cytology results: a meta-analysis of the HPV test positivity rate. J Cell Mol Med 2009;13:648-659.
11.
Arbyn M, Ronco G, Anttila A, Meijer CJ, Poljak M, Ogilvie G, Koliopoulos G, Naucler P, Sankaranarayanan R, Peto J: Evidence regarding human papillomavirus testing in secondary prevention of cervical cancer. Vaccine 2012;30(suppl 5):F88-F99.
12.
Arbyn M, Roelens J, Simoens C, Buntinx F, Paraskevaidis E, Martin-Hirsch PP, Prendiville WJ: Human papillomavirus testing versus repeat cytology for triage of minor cytological cervical lesions. Cochrane Database Syst Rev 2013;3:CD008054.
13.
Cogliano V, Baan R, Straif K, Grosse Y, Secretan B, El Ghissassi F; WHO International Agency for Research on Cancer: Carcinogenicity of human papillomaviruses. Lancet Oncol 2005;6:204.
14.
Bouvard V, Baan R, Straif K, Grosse Y, Secretan B, El Ghissassi F, Benbrahim-Tallaa L, Guha N, Freeman C, Galichet L, et al: A review of human carcinogens. Part B. Biological agents. Lancet Oncol 2009;10:321-322.
15.
Schiffman M, Clifford G, Buonaguro FM: Classification of weakly carcinogenic human papillomavirus types: addressing the limits of epidemiology at the borderline. Infect Agent Cancer 2009;4:8.
16.
Khan MJ, Castle PE, Lorincz AT, Wacholder S, Sherman M, Scott DR, Rush BB, Glass AG, Schiffman M: The elevated 10-year risk of cervical precancer and cancer in women with human papillomavirus (HPV) type 16 or 18 and the possible utility of type-specific HPV testing in clinical practice. J Natl Cancer Inst 2005;97:1072-1079.
17.
Saslow D, Solomon D, Lawson HW, Killackey M, Kulasingam SL, Cain J, Garcia FA, Moriarty AT, Waxman AG, Wilbur DC, 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. Am J Clin Pathol 2012;137:516-542.
18.
Belinson JL, Hu S, Niyazi M, Pretorius RG, Wang H, Wen C, Smith JS, Li J, Taddeo FJ, Burchette RJ, et al: Prevalence of type-specific human papillomavirus in endocervical, upper and lower vaginal, perineal and vaginal self-collected specimens: implications for vaginal self-collection. Int J Cancer 2010;127:1151-1157.
19.
Smith JS, Lewkowitz AK, Qiao YL, Ji J, Hu S, Chen W, Zhang R, Liaw KL, Esser M, Taddeo FJ, et al: Population-based human papillomavirus 16, 18, 6 and 11 DNA positivity and seropositivity in Chinese women. Int J Cancer 2012;131:1388-1395.
20.
Wu EQ, Liu B, Cui JF, Chen W, Wang JB, Lu L, Niyazi M, Zhao C, Ren SD, Li CQ, et al: Prevalence of type-specific human papillomavirus and pap results in Chinese women: a multi-center, population-based cross-sectional study. Cancer Causes Control 2013;24:795-803.
21.
Zhang R, Velicer C, Chen W, Liaw KL, Wu EQ, Liu B, Cui JF, Belinson JL, Zhang X, Shen GH, et al: Human papillomavirus genotype distribution in cervical intraepithelial neoplasia grades 1 or worse among 4,215 Chinese women in a population-based study. Cancer Epidemiol 2013;37:939-945.
22.
Ko V, Nanji S, Tambouret RH, Wilbur DC: Testing for HPV as an objective measure for quality assurance in gynecologic cytology: positive rates in equivocal and abnormal specimens and comparison with the ASCUS to SIL ratio. Cancer 2007;111:67-73.
23.
Musa J, Taiwo B, Goldsmith S, Sutton S, Berzins B, Murphy RL: Predictors of atypical squamous cell of undetermined significance cervical cytology with high-risk human papilloma virus genotypes. Arch Gynecol Obstet 2011;283:343-348.
24.
Castle PE, Schiffman M, Burk RD, Wacholder S, Hildesheim A, Herrero R, Bratti MC, Sherman ME, Lorincz A: Restricted cross-reactivity of hybrid capture 2 with nononcogenic human papillomavirus types. Cancer Epidemiol Biomarkers Prev 2002;11:1394-1399.
25.
Castle PE, Sideri M, Jeronimo J, Solomon D, Schiffman M: Risk assessment to guide the prevention of cervical cancer. Am J Obstet Gynecol 2007;197:356, e351-e356.
26.
Einstein MH, Martens MG, Garcia FA, Ferris DG, Mitchell AL, Day SP, Olson MC: Clinical validation of the Cervista HPV HR and 16/18 genotyping tests for use in women with ASC-US cytology. Gynecol Oncol 2010;118:116-122.
27.
Stoler MH, Wright TC Jr, 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;135:468-475.
28.
Castle PE, Glass AG, Rush BB, Scott DR, Wentzensen N, Gage JC, Buckland J, Rydzak G, Lorincz AT, Wacholder S: Clinical human papillomavirus detection forecasts cervical cancer risk in women over 18 years of follow-up. J Clin Oncol 2012;30:3044-3050.
29.
Arbyn M, Martin-Hirsch P, Wentzensen N: Human papillomavirus-based triage of women showing a cervical cytology result of borderline or mild dyskaryosis. BJOG 2010;117:641-644.
30.
Guo M, Gong Y, Wang J, Dawlett M, Patel S, Liu P, Bevers TB, Sneige N: The role of human papillomavirus type 16/18 genotyping in predicting high-grade cervical/vaginal intraepithelial neoplasm in women with mildly abnormal Papanicolaou results. Cancer Cytopathol 2012;121:79-85.
31.
Spinillo A, Dal Bello B, Gardella B, Roccio M, Dacco MD, Silini EM: Multiple human papillomavirus infection and high grade cervical intraepithelial neoplasia among women with cytological diagnosis of atypical squamous cells of undetermined significance or low grade squamous intraepithelial lesions. Gynecol Oncol 2009;113:115-119.
32.
Abraham J, Stenger M: cobas HPV test for first-line screening for cervical cancer. J Community Support Oncol 2014;12:156-157.
33.
Qiao YL, Sellors JW, Eder PS, Bao YP, Lim JM, Zhao FH, Weigl B, Zhang WH, Peck RB, Li L, et al: A new HPV-DNA test for cervical-cancer screening in developing regions: a cross-sectional study of clinical accuracy in rural China. Lancet Oncol 2008;9:929-936.
34.
Qiao YL, Jeronimo J, Zhao FH, Schweizer J, Chen W, Valdez M, Lu P, Zhang X, Kang LN, Bansil P, et al: Lower cost strategies for triage of human papillomavirus DNA-positive women. Int J Cancer 2014;134:2891-2901.
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