The impact of alternate HPV vaccination and cervical screening strategies in Japan: a cost-effectiveness analysis.

Background: The Japanese 2020 cervical screening guidelines recommend conventional cervical cytology screening every 2-years for women aged 20-69 years. The nonavalent human papillomavirus (HPV) vaccine has also recently been approved in Japan. We therefore evaluated the cost-effectiveness of cervical cancer screening strategies alongside universal nonavalent HPV vaccination of girls (12-16 years). Methods: A cost-effectiveness analysis was performed using an age-specific Markov microsimulation model for Japan to evaluate total costs, quality adjusted life-years (QALYs) gained, incremental cost-effectiveness ratios (ICER), colposcopies, biopsies, precancer and cervical cancer treatments for 29 combined vaccination and screening strategies (conventional cytology, liquid-based cytology (LBC), HPV testing, and HPV self-collection). A cohort of 100,000 girls (12-16 years old) over a lifetime offered the nonavalent HPV vaccine was used (current vaccination coverage = 0.08%, current screening coverage = 43.7%). A discount rate of 3% was applied to costs and QALYs. Univariate and probabilistic sensitivity analysis was performed to assess robustness of the findings. Costs were reported in US dollars (2023). Findings: Compared with conventional cytology, evaluated strategies would incur an additional cost of US$839,280-738,182,669 and gain 62,755-247,347 quality-adjusted-life-years. HPV testing distinguishing HPV16/18 with reflex LBC (3-yearly) would be most cost-effective (ICER = US$7511 per QALY gained). At a willingness-to-pay (WTP) of 1-times gross domestic product (GDP) per capita, the probability of it being cost-effective was 70%. At historically high vaccination coverage (70%) ICERs decreased overall but did not affect the ranking of the most cost-effective strategy. While a 5-yearly interval became more cost-effective than a 3-yearly interval. Including HPV self-collection for under-screened women made all strategies more cost-effective. Interpretation: At current cervical screening participation (43.7%) and low vaccination coverage (<1.0%), HPV testing distinguishing HPV16/18 with reflex LBC (3-yearly) would be the most cost-effective screening strategy compared to conventional cytology (2-yearly). Funding: Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (17H03589) and Grants of the National Cancer Center Japan (Gan Kenkyu Kaihatsuhi 31-A-20 and 2023-A-23).