Colposcopy referral and CIN3+ risk of human papillomavirus genotyping strategies in cervical cancer screening.

Abstract

High-risk human papillomavirus (hrHPV)-based cervical cancer screening in the Netherlands led to a substantial increase in number of colposcopy referrals and low-grade lesions detected. Genotyping strategies may be employed to lower the screening-related burden. We evaluated fourteen triage strategies with genotyping (HPV16/18 or HPV16/18/31/33/45/52/58) for hrHPV-positive borderline or mild dyskaryosis (BMD) or normal cytology, using data from a population-based hrHPV-based screening trial with 5-year interval (POBASCAM). We considered colposcopy referral at baseline, after 6-month repeat cytology and after 5-year hrHPV testing. Performance was evaluated by one-round positive and negative predictive value (PPV and NPV) for CIN3+ and by two-round colposcopy referral rate. To identify efficient strategies, they were ordered by the one-round colposcopy referral rate. Adjacent strategies were compared by the marginal PPV for detecting one additional CIN3+ (mPPV). The most conservative strategy (repeat cytology after BMD and HPV16/18/31/33/45/52/58-positive normal cytology, next round otherwise) yielded an mPPV of 28%, NPV of 98.2%, and colposcopy rate of 47.2%. Adding direct referral after BMD or genotype-positive BMD yielded an mPPV≤8.2%, NPV≥98.5% and an increase in colposcopy rate of 1.9-6.5%. Adding direct referral after HPV16/18-positive normal cytology yielded an mPPV≤3.5%, NPV≥99.5% and an increase in colposcopy rate of 13.9%. Direct colposcopy referral of women with BMD or normal cytology is unlikely to be efficient, but genotype-guided direct referral after BMD may be considered because the increase in colposcopies is limited. HrHPV screening programs can become very efficient when immediate colposcopy referral is limited to women at highest CIN3+ risk.