Del Mistro A, Adcock R, Carozzi F, Gillio-Tos A, De Marco L, Girlando S, Rizzolo R, Frayle H, Trevisan M, Sani C, Burroni E, Giorgi Rossi P, Cuzick J, Ronco G, NTCC Working Group

Int J Cancer. 2018 Feb 17. doi: 10.1002/ijc.31326



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 PCR 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 3 groups (A, B and C in decreasing order). Receiver Operating Characteristic (ROC) curves were computed.
Among 2255 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, 35), A or B (31, 52, 18, 59, 58) and A or B or C (39, 51, 56, 45, 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.


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