Public health impact and cost effectiveness of routine and catch-up vaccination of girls and women with a nine-valent HPV vaccine in Japan: a model-based study

Abstract

Background: Combined with cancer screening programs, vaccination against human papillomavirus (HPV) can significantly reduce the high health and economic burden of HPV-related disease in Japan. The objective of this study was to assess the health impact and cost effectiveness of routine and catch-up vaccination of girls and women aged 11-26 years with a 4-valent (4vHPV) or 9-valent HPV (9vHPV) vaccine in Japan compared with no vaccination.

Methods: We used a mathematical model adapted to the population and healthcare settings in Japan. We compared no vaccination and routine vaccination of 12-16-year old girls with 1) 4vHPV vaccine, 2) 9vHPV vaccine, and 3) 9vHPV vaccine in addition to a temporary catch-up vaccination of 17-26 years old girls and women with 9vHPV. We estimated the expected number of disease cases and deaths, discounted (at 2% per year) future costs (in 2020 ¥) and discounted quality-adjusted life years (QALY), and incremental cost effectiveness ratios (ICER) of each strategy over a time horizon of 100 years. To test the robustness of the conclusions, we conducted scenario and sensitivity analyses.

Results: Over 100 years, compared with no vaccination, 9vHPV vaccination was projected to reduce the incidence of 9vHPV-related cervical cancer by 86% (from 15.24 new cases per 100,000 women in 2021 to 2.02 in 2121). A greater number of cervical cancer cases (484,248) and cancer-related deaths (50,102) were avoided through the described catch-up vaccination program. Routine HPV vaccination with 4vHPV or 9vHPV vaccine prevented 5,521,000 cases of anogenital warts among women and men. Around 23,520 and 21,400 diagnosed non-cervical cancers are prevented by catch-up vaccination among women and men, respectively. Compared with no vaccination, the ICER of 4vHPV vaccination was ¥975,364/QALY. Compared to 4vHPV, 9vHPV + Catch-up had an ICER of ¥1,534,493/QALY.

Conclusions: A vaccination program with a 9-valent vaccine targeting 12 to 16 year-old girls together with a temporary catchup program will avert significant numbers of cases of HPV-related diseases among both men and women. Furthermore, such a program was the most cost effective among the vaccination strategies we considered, with an ICER well below a threshold of ¥5000,000/QALY.

Keywords: Anal; And oropharyngeal cancer; Cervical; Condylomata acuminate; Cost effectiveness analysis; Disease transmission models; Epidemiology; Genital warts; Herd protection/immunity; Human papillomavirus; Intraepithelial neoplasia; Japan; Oral cavity; Recurrent respiratory papillomatoses; Vaccines; Vaginal; Vulvar.

Fig. 1

Population-level health impact of routine and alternative strategies of vaccinating girls and women aged 12 through 26 years on 9-valent HPV-related (a) cervical cancer and (b) cervical cancer death. GOV-4vHPV included routine vaccination of 12–16-year old girls with 4vHPV from 2021 onwards; GOV-9vHPV included routine vaccination of 12–16-year old girls with 9vHPV; GOV + Catch-Up-9vHPV consisted of routine vaccination of 12–16-year old girls from 2021 onwards and temporary catch-up vaccination of 17–26 years old girls and women with 9vHPV until 2025. All vaccination strategies were combined with cervical cancer screening

Fig. 2

Population-level health impact of routine and alternative strategies of vaccinating girls and women aged 12 through 26 years on 9-valent HPV-related anogenital warts and other non-cervical cancers. a Diagnosed anogenital warts among women (arrows spanning the curves represent the incremental benefit between strategies). b Diagnosed anogenital warts among men. c Diagnosed non-cervical cancer among women d Diagnosed cancer among men.GOV-4vHPV included routine vaccination of 12–16-year old girls with 4vHPV from 2021 onwards; GOV-9vHPV included routine vaccination of 12–16-year old girls with 9vHPV; GOV + Catch-Up-9vHPV consisted of routine vaccination of 12–16-year old girls from 2021 onwards and temporary catch-up vaccination of 17–26 years old girls and women with 9vHPV until 2025. All vaccination strategies were combined with cervical cancer screening

Fig. 3

Tornado diagrams for the ICERs, including all HPV-related disease. ICER = incremental cost-effectiveness ratio; HPV = human papillomavirus; ¥ = Japanese Yen. Girls-only vaccination with 4vHPV included routine vaccination of 12–16-year old girls with 4vHPV from 2021 onwards; Girls-only routine and catch-up vaccination with 9vHPV consisted of routine vaccination of 12–16-year old girls from 2021 onwards and temporary catch-up vaccination of 17–26 years old girls and women with 9vHPV until 2025. All vaccination strategies were combined with cervical cancer screening