Cost-effectiveness analysis of human papillomavirus (HPV) genotyping strategies for management of HPV-positive women in cervical cancer screening.

In 2017, the Netherlands introduced primary human papillomavirus (HPV)-based screening with cytology triage, which increased colposcopy referrals and low-grade lesions detected. In 2022, HPV16/18 genotyping was added for women with borderline/low-grade cytology. Triage with HPV genotyping may better balance screening benefits, harms, and costs. Therefore, we evaluated the cost-effectiveness of 19 triage strategies based on net monetary benefit (NMB) at cost-effectiveness thresholds of €20,000 and €50,000/quality-adjusted life-year (QALY), with the highest NMB indicating the most cost-effective strategy. Triage tests included 16/18 genotyping, 7-type (16/18/31/33/45/52/58) genotyping, and cytology (high-grade squamous intraepithelial lesions [HSIL]: moderate/severe, atypical squamous cells of undetermined significance [ASC-US]/low-grade squamous intraepithelial lesions [LSIL]: borderline/low-grade, negative for intraepithelial lesion or malignancy [NILM]: normal). Effects on cancer incidence and mortality were obtained by combining POBASCAM trial data with nationwide screening and cancer registries. Time since the onset of high-grade lesion (cervical intraepithelial neoplasia [grade 2/3] [CIN2/3]) at baseline of the Population-based Screening Study Amsterdam trial cannot be estimated from the data and was varied between 0 and 10 years. At a €20,000/QALY threshold, immediate referral for HSIL and 16/18-positive ASC-US/LSIL, and repeat cytology for 16/18-negative ASC-US/LSIL and 7-types positive NILM had the highest NMB (€214.1 to €309.3/woman gained compared to referring all HPV-positive women). At a €50,000/QALY threshold, immediate referral for all 16/18-positives and/or HSIL, and repeat cytology for 16/18-negative ASC-US/LSIL and 7-types positive NILM had the highest NMB if time since onset of CIN2/3 was greater than 2 years. Cytology combined with HPV16/18 and extended genotyping is cost-effective for triage of HPV-positives. Immediate colposcopy referral of all HPV16/18-positives is cost-effective at a €50,000/QALY threshold.