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

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).

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).

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.

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).

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).