Combined Use Of Cytology, P16 Immunostaining And Genotyping For Triage Of Women Positive For High Risk Human Papillomavirus At Primary Screening.

HPV testing is very sensitive for primary cervical screening but has low specificity. Triage tests which improve specificity but maintain high sensitivity are needed. Women enrolled in the experimental arm of phase 2 of the NTCC randomised controlled cervical screening trial were tested for high risk human papillomavirus (hrHPV) and referred to colposcopy if positive. hrHPV positive women also had HPV genotyping (by PCR with GP5+/GP6+ primers and reverse line blotting), immunostaining for p16 overexpression and cytology. We computed sensitivity, specificity and positive predictive value (PPV) for different combinations of tests, and determined potential hierarchical ordering of triage tests. 1091 HPV positive women had valid tests for cytology, p16 and genotyping. Ninety two of them had CIN2+ histology and 40 CIN3+. The PPV for CIN2+ was >10% in hrHPV positive women with HSIL+ (61.3%), LSIL+ (18.3%) and ASC-US+ (14.8%) cytology, p16 positive (16.7%) and, hierarchically, for infections by HPV33, 16, 35, 59, 31 and 52 (in decreasing order). Referral of women positive for either p16 or LSIL+ cytology had 97.8% sensitivity for CIN2+ and women negative for both of these had a 3-year CIN3+ risk of 0.2%. Similar results were seen for women either p16 or HPV16/33 positive. hrHPV positive women who were negative for p16 and cytology (LSIL threshold) had a very low CIN3+ rate in the following three years. Recalling them after that interval and referring those positive for either test to immediate colposcopy seems an efficient triage strategy. The same applies to p16 and HPV16. This article is protected by copyright. All rights reserved.