Introduction
Cervical cancer has the fourth highest mortality (7.5%) among all cancers in women. Additionally, it has the third highest incidence rate (7.9%) (1). A trend for both the morbidity and mortality associated with cervical cancer are increasing in Japan. An average number of the incidence from 2016 to 2019 were 2816 (might be more than 3000 if uterine cancer of unknown origin were accounted), and that of the mortality from 2012 to 2021 were 2816 in Japan. The peak of age for the incidence was 45-49 and 65-69 years old. Annual numbers of death of women aged 20-49 years being in the reproductive age or are mothers taking care of young children are 479 – 656 (average was 503) in 2012 – 2021. Therefore, many young women are suffered from cervical cancer, and about one third (32%) (2016-2021) annually die in Japan (2). The increased prevalence of cervical cancer among young women appears to be driven by social factors.
More than 90% of cervical cancer cases are caused by human papillomavirus (HPV) (3). Among more than 200 types of HPV identified thus far, 13 to 14 are considered to cause cervical cancer; these types are regarded as high-risk HPV types. Among them, HPV16 and HPV18 are the most widespread; they have been identified in approximately 70% of women with cervical cancer in Western countries (4) and in 50% to 68% of women with cervical cancer in Japan (5, 6). The World Health Organization has declared that cervical cancer would be eliminated within this century if 90% of women received HPV vaccination, 70% underwent cervical cancer screening, and 90% received treatment for cervical premalignant lesions (7). Nationwide reductions in high-grade cervical intraepithelial neoplasia (CIN2 and CIN3) after administration of the bivalent vaccine were reported in Scotland (8). Additionally, decreases in cervical cancer after bivalent or quadrivalent HPV vaccination were reported in Australia (9), Sweden (10), and the United Kingdom (11). The prevalences of cervical cancer caused by HPV16 and HPV18 infections, which are targeted by any types of prophylactic HPV vaccines, have considerably decreased in several countries (9, 12–16). Cross-protection against HPV16- and HPV18-related types has been suggested (9–16), but there has been no increase in infections caused by non-vaccine HPV types (15, 16).
In Japan, the bivalent HPV vaccine was licensed in October 2009, and the quadrivalent vaccine was licensed in July 2011 (Fig.1). A special funding program with 50% support from the Japanese government and 50% from local governments was implemented in October 2010 in Japan. Beginning in April 2013, the bivalent and quadrivalent HPV vaccines were both included in the Japanese National Immunization Program for girls aged 12 to 16 years. However, after the Japanese media published sensational reports of so-called “diverse symptoms,” the Japanese Ministry of Health, Labour and Welfare suspended proactive recommendations for the HPV vaccine in June 2013—only 2 months after implementation of the national HPV vaccine program. Thereafter, vaccine coverage dramatically decreased from > 70% to < 1% among girls eligible for free vaccination. The vaccine crisis from 2013 to 2019 is expected to result in an additional 24,600 to 27,300 cases and 5000 to 5700 deaths over the lifetime of cohorts born from 1994 to 2007, compared with a scenario where coverage remained at approximately 70% since 2013 (17). Beginning in April 2022, Japan reinstated the recommendation for nationwide HPV vaccination (18). Nevertheless, a substantial effort will be required in Japan to raise vaccine coverage among girls aged 12 to 16 years and among women aged 16 to 26 years in 2023—these women belong to the catch-up generation born between April 1, 1997 and April1, 2007. The vaccine coverage for this age group must be improved from its previous level, which ranged from 68% to 76% (18).
Importantly, some women within this age group received bivalent or quadrivalent prophylactic HPV vaccines in Japan. Therefore, several studies have evaluated the efficacies of these vaccines (19–21). Reductions in the prevalences of HPV16 and HPV18 after vaccination were reported in Akita Prefecture, Japan (19). Reductions in the prevalences of HPV31, HPV45, and HPV52 after vaccination were also observed in a cross-sectional study of individuals in Niigata, Japan, suggesting cross-protection against these types (21). Moreover, lower incidences of CIN2/3 or adenocarcinoma in situ among patients who tested positive for HPV16 or HPV18 were reported in a nationwide case–control study (22).
We previously conducted a population-based study to investigate the prevalences of HPV and abnormal cytology from 2011 to 2013 in Japan [Japanese HPV Disease Education and Research Survey (J-HERS)] (23). Here, we performed a similar study, the J-HERS 2021, to explore the prevalences of HPV infection and cervical abnormalities after implementation of the national HPV vaccination program. This is the first Japanese study to investigate the efficacy of HPV vaccination in reducing the prevalences of cervical abnormalities and HPV infection through comparisons between pre-vaccination and post-vaccination periods.