Primary hrHPV DNA testing in cervical cancer screening: How to manage screen-positive women? a POBASCAM trial substudy

Background: High-risk human papillomavirus (hrHPV) testing has higher sensitivity but lower specificity than cytology for cervical (pre)-cancerous lesions. Therefore, triage of hrHPV-positive women is needed in cervical cancer screening. Methods: A cohort of 1,100 hrHPV-positive women, from a population-based screening trial (POBASCAM: n = 44,938; 29-61 years), was used to evaluate 10 triage strategies, involving testing at baseline and six months with combinations of cytology, HPV16/18 genotyping, and/or repeat hrHPV testing. Clinical endpoint was cervical intraepithelial neoplasia grade 3 or worse (CIN3+) detected within four years; results were adjusted for women not attending repeat testing. A triage strategy was considered acceptable, when the probability of no CIN3+ after negative triage (negative predictive value, NPV) was at least 98%, and the CIN3+ risk after positive triage (positive predictive value, PPV) was at least 20%. Results: Triage at baseline with cytology only yielded an NPV of 94.3% [95% confidence interval (CI), 92.0- 96.0] and a PPV of 39.7% (95% CI, 34.0-45.6). An increase in NPV, against a modest decrease in PPV, was obtained by triaging