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.