Intentions for catch-up HPV vaccination in Japan: an internet survey

Of the more than 200 types of human papillomavirus (HPV) known to infect humans, 14 have a high risk of causing cervical cancer. Two strains, HPV16 and HPV18, are associated with 70% of all cervical cancers worldwide, and roughly 60% in Japan [1‐3]. HPV16 and 18 account for about 530,000 cervical cancer cases per year worldwide. HPV16/18 are also the most common strains in men’s HPV-related oropharyngeal cancer, accounting for 30,000 cases per year worldwide [4]. The main route of HPV transmission is sexual mucosal skin contact. Use of a condom will reduce HPV transmission to the cervix, but does not prevent it completely [5].

Over recent decades in Japan, the incidence of cervical cancer among young females has been increasing, and the peak incidence has been shifting to ever younger age groups [6]. With the introduction of the HPV vaccine as an effective countermeasure against the increasing cervical cancer and a public-funded vaccination program, there were great expectations for reducing these trends. Subsidies from the national and local governments for programs for bivalent-vaccination of girls aged 13–16 began in 2010. By 2013, both bivalent and quadrivalent HPV vaccines were being used routinely for vaccinating girls aged 12–16 as part of the National Immunization Program.

However, in June of 2013, due to media reports of possible post-vaccination adverse symptoms, Japan’s Ministry of Health, Labor, and Welfare (MHLW) decided to temporarily suspend the national immunization program’s recommendation for routine HPV vaccination [7]. As a result, the HPV vaccination rate for girls born in or after 2000 declined dramatically [8].

In December of 2015, the World Health Organization (WHO) Global Advisory Committee for Vaccine Safety issued a statement on HPV vaccine safety [9, 10], warning the Japanese government that “policy decisions based on weak evidence, leading to lack of use of safe and effective vaccines, can result in real harm.” (WHO) WHO’s warnings were not heeded, and Japan’s policy decisions based on weak evidence for adverse events led to a lack of use of the safe and effective vaccine [10, 11]. To counter the negative publicity, the vaccine was receiving, in April 2017, a nationwide epidemiological survey, led by a research team appointed by the MHLW, concluded that the putative “adverse symptoms” were not specific to females who were vaccinated [12‐14].

In November of 2021, the MHLW’s “temporary suspension” of its active vaccination recommendation finally ended. The feared unwarranted ill effects of nearly 9 years of little to no HPV vaccinations nationwide have become the new reality.

The historical HPV vaccination rate, and thus the potential for infection, now varies greatly in Japan, depending on a girl or woman’s fiscal year (FY) of birth [15]. Sekine et al. reported the HPV infection rates among females aged 20–21 years old who were targeted for cervical cancer screening in the FY 2014–2020. They showed that infection rates increased for those born in 2000, the vaccine-suspended generation [10]. Furthermore, our group has reported that an increased rate of cervical cytological abnormalities is also occurring in the vaccine-suspended generation [11].

Recognizing that there is a tremendous added risk for cervical cancer for this “poorly vaccinated gap generation”, i.e., in those women who failed to get vaccinated during the 8 years when the government withheld its recommendation for doing so, Japan is now offering to cover the costs of their “catch-up vaccination”. The MHLW announced that these catch-up vaccinations would be administered from April of 2022 to March of 2025 for those born between 1997 and 2005 [16]. In addition, a 9-valent HPV vaccine (covering five additional high-risk types of HPV) is introduced into the routine vaccination program in April of 2023.

A previous study reported the pattern of HPV vaccine hesitancy among the catch-up generations in Japan [17], but the reasons for their intention to be vaccinated were not analyzed. Increasing the early catch-up vaccination rate is essential for cervical cancer control in Japan. In our study, more detailed information including intention for catch-up vaccination was collected and analyzed. We have conducted an internet survey to quantify the vaccination intentions and characteristics of those currently eligible for catch-up vaccination to determine where and how we need to apply assistance to that goal.

We conducted an internet survey of young women in Japan who were at that time beyond the normal grade school age of eligibility to receive a publicly subsidized HPV vaccination, but were now qualified for a government-recommended catch-up vaccination program meant to compensate them for 8 years of lapsed HPV vaccinations. We found that these young women’s intention to receive the catch-up vaccination was heavily associated with their prior history of gynecological visits, sexual activity, degree of anxiety about cervical cancer, intention to receive cervical cancer screening, familiarity with problems related to cervical cancer, whether they had received a recommendation for the vaccination from family, and their knowledge regarding cervical cancer.

The survey found that, compared to the “I want to be HPV vaccinated” group, the “Unable to determine my vaccination intention” and “I do not want to be vaccinated” groups were about twice as likely to answer they were afraid of the vaccine’s potential adverse side effects. The group who wanted to be vaccinated had a better history of gynecological visits, had a higher intention to receive cervical cancer screening, and were more knowledgeable about the cervical cancer. Furthermore, if they already had sexual intercourse, they were more anxious about their risks of cervical cancer. Therefore, we think they were more cognitive that “infection prevention meant cervical cancer prevention”, and thus they had a higher intention to be vaccinated, even though they too were afraid of the reported potential for adverse vaccination events.

Unexpectedly, there was a significantly lower proportion of respondents who wanted the catch-up HPV vaccination in the “vaccinated generation” compared to the “vaccine-suspended generation”. We are guessing that the reason for this surprising result is that the survey respondents from the “vaccinated generation” who were now refusing the catch-up vaccination were actually the small number of originally unvaccinated girls who now, years later, are being consistent with their previous choice not to be vaccinated.

This negative outcome is consistent with known human behavior that, once a stance has been chosen, it seldom changes without drastic reasons to do so. We assume that the vaccination rate among the “unvaccinated generation” has a higher possibility of benefiting from now providing them with targeted accurate information. This hope is because girls were born in FY2000 and later were at one time motivated to be vaccinated but then refrained, primarily in response to spurious reports of vaccination adverse side effects and the withdrawal of MHLW’s recommendation for the vaccination.

Knowing which women still need to be vaccinated depends on accessing their medical vaccination records. In Japan, under the Immunization Law, it is the local governments that are responsible for maintaining vaccination history data. However, the minimal data retention period, set at 5 years, has passed or will soon pass for these women, and some local governments have already begun discarding the very data we desperately need [20].

We found that the respondent’s COVID vaccination status and their intention to seek a COVID vaccination were well associated with their intention to also receive the HPV catch-up vaccination. The group who most wanted to be vaccinated was also more receptive to the COVID vaccine. This suggests to us that it might be more effective to match the specific catch-up HPV vaccination recommendation message to the number of COVID vaccination shots that the targeted woman has had.

In addition, in this survey, interesting findings were obtained regarding cervical cancer screening, which is important as secondary prevention of cervical cancer. The rate of respondents who had received a cervical cancer screening was less than half of the rate of those who answered that they had visited a gynecologist before. It was suggested that although younger females had opportunities to visit a gynecologist, these opportunities have not been connected to cervical cancer screening [21].

Like the results of a previous study that “parental intention to vaccinate and having a friend who had engaged in sexual intercourse were significant independent predictors of adolescents’ intent to accept STI vaccination” [22], our survey showed the group with high receptivity to the catch-up vaccination had their own sexual experience and their families had recommended vaccination. Several other reports have indicated that parental acceptance is important for immunization [23, 24]. In addition, a recommendation from a health care provider was shown to be associated with vaccine acceptability among parents [25‐27]. In our survey, as mentioned earlier, the result was “the group who wanted to be vaccinated had a better history of gynecological visits, had a higher intention to receive cervical cancer screening, and were more knowledgeable about the cervical cancer”, which suggests that they may have obtained knowledge about screening and cervical cancer at the clinic. On the hand, a recommendation by a health care provider may be not enough to motivate mothers to vaccinate their daughters [28]. In the survey by Khodadadi et al., 35.3% of 317 respondents hesitated to vaccinate their daughters even when recommended by a doctor. They mentioned as follows, “Further efforts should focus on increasing awareness regarding HPV and cervical cancer, heightening perceived risk of HPV infection among daughters and boosting self-efficacy to get their children vaccinated against HPV”. We believe these efforts are important to increase the low vaccination rate in Japan as well. Because in our study, even in the high vaccination intention group, only 22% of the family members recommended the catch-up vaccination, and in the low vaccination intention group, less than 10% of the family members recommended the catch-up vaccination. More parents in Japan hesitate to vaccinate their children than in other countries [29].

Vaccine hesitancy is complex and context specific [30]. It is influenced by a wide variety of factors, including time, place, vaccine type, individual characteristics, social environment, and culture. Like our report this time, Machida et al. also reported that the HPV vaccine was highly accepted among those who received the COVID-19 vaccine. It would be effective to strengthen recommendations for this group first [17].

One of the limitations of our study is that we stratified the respondents into groups based on the birth FY, so the average age of the respondents was unavoidably significantly different in each group. In addition, we compared between the vaccinated generation and the vaccine-suspended generation, but it might be a comparison by different age groups. However, the social impact of the Japanese government’s decision has been significant, drastically reducing HPV vaccination rates. This impact is considered stronger than the impact of age on vaccination intentions. Second, the respondents were monitor members already enrolled in the consumer panel. Because the respondents have chosen to respond to this survey, some kind of sample selection bias may exist. In addition, generalizing the present results obtained from the internet survey may be problematic in view of the correspondence between the survey methodology and the respondent populations.

In conclusion, we have quantified the vaccination intentions and characteristics of the population of young women currently eligible for targeted catch-up HPV vaccination. The ages of those who were eligible for catch-up immunization in the year the catch-up immunization began (FY2022) were 17–25. In Japan, the current rate for female sexual intercourse experience at age 17 is about 25%. However, this rate increases significantly, to about 80%, by age 25. (JFPA) We need to encourage targeted females to start catch-up vaccinations as early as possible. It is necessary for all organizations involved with females eligible for HPV vaccination and their parents, such as government, medical institutions, and educational institutions, to make recommendations based on an understanding of the characteristics of the “vaccinated generation” and the “vaccine-suspended generation”.