Human papillomavirus vaccine impact on invasive cervical cancer in Japan: Preliminary results from cancer statistics and the MINT study

Abstract

The first prophylactic vaccine against human papillomavirus (HPV) 16 and HPV18 was licensed in Japan in 2009. HPV vaccine effectiveness against high-grade cervical lesions has been demonstrated among young Japanese women, but evidence of its effects on invasive cervical cancer (ICC) is lacking. Using data from two different cancer registries, we compared recent trends of new ICC cases by age group using Poisson regression analysis. We also analyzed time trends in HPV16/18 prevalence among 1414 Japanese women aged <40 years newly diagnosed with ICC in the past decade. Based on the population-based cancer registry, the incidence of ICC among young women aged 20-29 years showed a significant decline from 3.6 to 2.8 per 100 000 women-years during 2016-2019, but no similar decline was observed for older age groups (p < 0.01). Similarly, using data from the gynecological cancer registry of the Japan Society of Obstetrics and Gynecology, the annual number of ICCs among women aged 20-29 years also decreased from 256 cases to 135 cases during 2011-2020 (p < 0.0001). Furthermore, a declining trend in HPV16/18 prevalence in ICC was observed only among women aged 20-29 years during 2017-2022 (90.5%-64.7%, p = 0.05; Cochran-Armitage trend test). This is the first report to suggest population-level effects of HPV vaccination on ICC in Japan. Although the declining trend in HPV16/18 prevalence among young women with ICC supports a causal linkage between vaccination and results from cancer registries, further studies are warranted to confirm that our findings are attributable to vaccination.

Keywords: cancer registry; cervical cancer; human papillomavirus; incidence; vaccination.

FIGURE 1

Trends in invasive cervical cancer incidence in Japan by age group: Population‐based cancer registry, 1975–2019. Time trends in invasive cervical cancer incidence stratified by age group were based on data of the national estimates of cancer incidence (1975–2015, green background) and the national cancer registry (2016–2019, pink background).

FIGURE 2

Trends in annual numbers of invasive cervical cancer in Japan by age group: Japan Society of Obstetrics and Gynecology (JSOG) gynecological cancer registry, 2003–2020. Lines and left axis (logarithmic scale) show the annual number of cases newly diagnosed with invasive cervical cancer (ICC) in each calendar year, as indicated on the x‐axis, by age group; black bars and right axis indicate the number of hospitals participating in the JSOG cancer registry in the indicated year. Although the number of the JSOG registry hospitals continued to increase from 247 institutions in 2003 to 473 institutions in 2020, the annual number of new ICC cases among women aged 20–29 years peaked in 2011 and decreased thereafter.

FIGURE 3

Trends in attribution of HPV16 and HPV18 to invasive cervical cancer by age group: The MINT study, 2011–2022. Year‐on‐year trends of HPV16/18 prevalence (broken lines) and estimated prevalence trends (straight lines) among women diagnosed with invasive cervical cancer are shown for two age groups (20–29 years [red] and 30–39 years [green]). Asterisks indicate a marginally significant decline (p = 0.05).