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Int J Cancer. 2018 Jul 15;143(2):333-342. doi: 10.1002/ijc.31326. Epub 2018 Mar 9.

Human papilloma virus genotyping for the cross-sectional and longitudinal probability of developing cervical intraepithelial neoplasia grade 2 or more.

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Veneto Institute of Oncology IOV-IRCCS, Padua, Italy.
Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, UK.
Institute for Cancer Study and Prevention (ISPO), Florence, Italy.
Cancer Epidemiology-CERMS, University of Turin, Italy.
Pathology Unit, S. Chiara Hospital, Trento, Italy.
Center for Cancer Epidemiology and Prevention (CPO), Turin, Italy.
Epidemiology Unit, AUSL Reggio Emilia, IRCCS, Reggio Emilia, Italy.


Human papilloma virus (HPV) testing is more sensitive but less specific than cytology. We evaluated stand-alone genotyping as a possible triage method. During a multicentre randomised controlled trial comparing HPV testing to conventional cytology, HPV-positive women were referred to colposcopy and followed up if no high-grade lesion was detected. HPV-positive samples were genotyped by GP5+/GP6+ primed polymerase chain reaction followed by reverse line blot. Genotypes were hierarchically ordered by positive predictive value (PPV) for CIN grade 2 or more (CIN2+), and grouped by cluster analysis into three groups (A, B and C in decreasing order). Receiver operating characteristic curves were computed. Among 2,255 HPV-positive women with genotyping, 239 CIN2+ (including 113 CIN3+) were detected at baseline or during a 3-year follow-up. HPV33 had the highest PPV with CIN2+ and CIN3+ as the endpoint and when considering lesions detected at baseline or also during follow-up. HPV16 and HPV35 were the second and third, respectively. Cross-sectional sensitivity for CIN2+ at baseline was 67.3% (95% CI 59.7-74.2), 91.8% (95% CI 86.6-95.5) and 94.7% (95% CI 90.2-97.6), respectively, when considering as "positive" any of the HPV types in group A (33, 16 and 35), A or B (31, 52, 18, 59 and 58) and A or B or C (39, 51, 56, 45 and 68). The corresponding cross-sectional PPVs for CIN2+ were 15.8% 95% (CI 13.2-18.7), 12.0% (95% CI 10.3-13.9) and 9.6% (95% CI 8.2-11.1), respectively. HPV33, 16 and 35 confer a high probability of CIN2+ but this rapidly decreases when adding other genotypes.


HPV; cervical screening; genotyping; triage

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