ABSTRACT
Despite the initiation of catch-up human papillomavirus (HPV) vaccination in Japan in April 2022, uptake remains suboptimal. Understanding determinants of vaccination behavior is essential to develop effective strategies to improve coverage. We aimed to identify factors associated with HPV vaccination acceptance in the target population. An online survey was conducted in May 2024 among all students at Saga University (n = 5777) using a web-based questionnaire. The survey included 30 items covering background characteristics, knowledge about HPV vaccine, and attitudes toward HPV vaccine. Female respondents aged 17–27 y, corresponding to the catch-up HPV vaccination target population, were included. Factors associated with vaccination acceptance were examined using multivariable logistic regression, adjusting for possible confounders related to baseline characteristics, knowledge, and attitudes. Data from 406 female respondents were analyzed, including 275 in the acceptance and 131 in the non-acceptance groups (acceptance rate, 68%). The median age was 20 y (interquartile range [IQR], 19–21) in both groups. The proportions of participants with ≥3 doses of COVID-19 vaccine (77% versus 59%) and those enrolled in the Faculty of Medicine (45% versus 15%) were higher in the acceptance group. Adequate knowledge about free vaccination (adjusted odds ratio [aOR] 3.86), routine vaccination (aOR 5.72), and obligation to make efforts to receive vaccination (aOR 2.21) were positively associated with acceptance, whereas anxiety about vaccination was negatively associated (aOR 0.37). These findings suggest that targeting knowledge gaps and vaccine-related anxiety through interventional studies may be key to improving HPV vaccine uptake in the catch-up generation.
KEYWORDS: HPV vaccine, vaccine hesitancy, catch-up vaccination, anxiety, young adults, Japan
Introduction
Human papillomavirus (HPV) is a sexually transmitted virus, and persistent infection can cause cervical, vaginal, vulvar, penile, anal, or oropharyngeal cancer, as well as anogenital warts.1 Worldwide, an estimated 690,000 HPV-related cancer cases occur annually, with cervical cancer accounting for the largest disease burden and constituting a major public health concern.2 HPV-related cancers are vaccine-preventable; therefore, in 2020, the World Health Organization (WHO) introduced a global strategy aimed at accelerating the elimination of cervical cancer.3 As of February 2025, HPV vaccine had been incorporated into the national immunization programs of 148 WHO member states, representing 76% of all member states.4
In Japan, free HPV vaccination was incorporated into the national immunization program for girls aged 12–16 y in April 2013. Initially, nationwide HPV vaccination coverage was high, exceeding 70%.5 However, in June 2013, the Ministry of Health, Labor and Welfare suspended its proactive recommendation of HPV vaccination following sensational media reports of adverse events, despite an unclear causal relationship. Consequently, HPV vaccination coverage declined to below 1% and remained at this level for an extended period.5 After an approximately 9 y interval, the government resumed its recommendation in April 2022 and launched a publicly funded catch-up HPV vaccination program targeting unvaccinated females born between fiscal years (FY) 1997 and 2007. The catch-up period was originally set from April 2022 to March 2025. A transitional measure permitted eligible individuals who had received the first dose of vaccination by March 2025 to complete the full vaccination series through March 2026. Nevertheless, HPV vaccination uptake has remained suboptimal, with approximately one-half to one-third of the coverage observed in other high-income countries.4 Previous studies have suggested that safety concerns, insufficient knowledge about HPV vaccine, and low vaccine confidence may contribute to vaccine hesitancy.6,7 However, most existing studies have focused on adolescents or parents, leaving the determinants of vaccination behavior among the young adult catch-up generation remain poorly understood. To address this 9 y gap, often referred to as the vaccine crisis, promotion of catch-up vaccination is essential. Accordingly, the aim of this study was to investigate the factors associated with HPV vaccination acceptance within this target population.
Materials and methods
Study design and settings
This cross-sectional study was designed to assess factors associated with HPV vaccination behavior using a web-based questionnaire. The survey targeted students enrolled at Saga University in Japan and was conducted in May 2024. Prior to launching a campaign to promote catch-up HPV vaccination within the university, a questionnaire survey was conducted to assess vaccination intention and to clarify the current status of uptake among the target population. This comprehensive university comprises six faculties: Education, Science and Engineering, Agriculture, Economics, Medicine, and Art and Regional Design. The university currently has more than 6500 undergraduates and graduates. In Japan, a publicly funded catch-up vaccination program targeting unvaccinated females born between FY 1997 and 2007 was initiated in April 2022. Thus, this survey was conducted approximately 2 y after the initiation of the catch-up HPV vaccination program and 10 months before the deadline for receiving the first dose. An invitation to participate in the survey was sent to all undergraduate students, and participation was voluntary.
This study was approved by the Institutional Review Board of Saga University Hospital (approval number: 2024-01-R-12) and conducted in accordance with the principles of the Declaration of Helsinki. Informed consent was obtained electronically from all respondents prior to participation by requiring them to check a consent box.
Participant enrollment
The survey was administered via the university’s student academic information system (portal site), through which all enrolled undergraduate students across all faculties were simultaneously invited to participate in May 2024 (n = 5777), including both male (n = 3242) and female (n = 2535) students. A reminder invitation was sent two weeks after the initial invitation. For the analysis, female respondents aged 17–27 y were included, corresponding to the population targeted by the catch-up HPV vaccination program, which was offered to unvaccinated females born between FY 1997 and 2007. Responders were excluded if they declined to participate, declined to disclose sex, were male, or were aged ≥28 y.
Questionnaire and definitions
The survey comprised 30 items, including informed consent and questions on background characteristics, such as faculty affiliation, age, and sex (Supplementary Table S1). The questionnaire also assessed knowledge about HPV vaccine, including vaccination program, vaccine effectiveness, and safety. Attitudes toward HPV vaccine were evaluated using items assessing anxiety about the vaccine and the belief that everyone should be vaccinated. The survey also included items on HPV vaccination status and reasons for acceptance or non-acceptance. Participants were allowed to decline participation in this study and to withhold disclosure of their sex and sexual history. Multiple responses were permitted for questions regarding social media platforms used, primary sources of information, and reasons for acceptance or non-acceptance of HPV vaccination.
In the analysis, responses of “yes” or “have heard of it” were considered indicative of having the relevant knowledge or attitude. Participants who had already been vaccinated or had scheduled vaccination were classified into the acceptance group, whereas those who were hesitant about or refused vaccination were classified into the non-acceptance group.
Statistical analysis
Characteristics related to background variables, knowledge, and attitude were compared between the acceptance and non-acceptance groups. The chi-square test or Fisher’s exact test was used for categorical variables, and the Mann–Whitney U test was used for continuous variables. Logistic regression analysis was performed to identify potential factors associated with acceptance of HPV vaccination, with results expressed as odds ratios (ORs) and 95% confidence intervals (CIs). Statistical significance was defined as a two-tailed p value < .05, using 95% CI. A multivariate logistic regression model was used to identify factors independently associated with acceptance. The multivariable model was adjusted using a forced entry method for 13 covariates related to baseline characteristics, knowledge about HPV vaccine, and attitudes toward HPV vaccination. The 13 covariates included baseline characteristics (COVID-19 vaccination ≥3 doses, sexual history, and enrollment in the Faculty of Medicine), knowledge-related factors (awareness of catch-up vaccination, free vaccination, routine vaccination, obligation to receive vaccination and proximity to the deadline for free catch-up vaccination, perceived prevention of diseases other than cervical cancer, perceived preventive effectiveness even after sexual debut, and belief in no causal relationship with the media-reported serious adverse events), and attitudinal factors (anxiety and belief that everyone should be vaccinated), which were selected a priori based on clinical relevance and previous reports.8–10 To ensure model stability, the variable regarding awareness of the HPV vaccine’s existence was excluded due to its conceptual overlap with other knowledge-related variables. Variables specific to males were also excluded. Furthermore, for a sensitivity analysis, participants were classified into those who had already received HPV vaccination and all others (including those planning to be vaccinated and those who were hesitant or refused). Factors associated with HPV vaccination were examined using multivariable logistic regression analysis. All analyses were performed using JMP version 18 (SAS Institute Japan Ltd., Tokyo, Japan).
Results
Characteristics between acceptance and non-acceptance groups
Among the potentially eligible students enrolled at Saga University (n = 5777), 552 responded to the online survey, representing a response rate of 9.6%. Of 2535 female students, 418 responded to the survey, yielding a secondary response rate of 16.5%. Of the 552 respondents, 146 were excluded, leaving 406 female respondents included in the analysis: 275 in the acceptance group and 131 in the non-acceptance group (Figure 1). The overall HPV vaccine acceptance rate was 68%, of which 48% had received at least one dose (including 26% who had completed the full three-dose series), and 20% were planning to be vaccinated. Acceptance rates varied across faculties, with the highest rate observed in the Department of Medicine, Faculty of Medicine (91%), followed by the Department of Nursing, Faculty of Medicine (78%), and the Faculty of Agriculture (65%). The median age was 20 y (interquartile range, 19–21 y) in both groups (p = .44, Table 1). Most participants were aware of or had heard of the HPV vaccine, including 99% in the acceptance group and 93% in the non-acceptance group. Participants who had received ≥ 3 doses of COVID-19 vaccination (77% versus 59%, p < .0001) and those enrolled in the Faculty of Medicine (45% versus 15%, p < .0001) were more frequent in the acceptance group than in the non-acceptance group. Participants in the acceptance group also had greater knowledge of the HPV vaccination program in Japan, including awareness of catch-up vaccination, free vaccination, routine vaccination, the obligation to receive vaccination, and the deadline for catch-up vaccination (p < .0001 for all). Adequate knowledge of HPV vaccine efficacy, including prevention of diseases other than cervical cancer, preventive effectiveness even after sexual debut, availability of vaccination for men, and the benefit of vaccination for men, was also more common in the acceptance group. Awareness of the absence of a causal relationship between the vaccine and media-reported serious adverse events was more frequent in the acceptance group (29% versus 5%, p < .0001). In contrast, anxiety toward HPV vaccination was more common in the non-acceptance group (31% versus 59%, p < .0001).
Figure 1.
Flow diagram of respondent selection and enrollment.
Table 1.
Characteristics of respondents by HPV vaccination acceptance (n = 406).
| Characteristics | Total (n = 406) | Acceptance (n = 275) | Non-acceptancea (n = 131) | p-value |
|---|---|---|---|---|
| Age (years), median (IQR) | 20 (19–21) | 20 (19–21) | 20 (19–21) | .44 |
| COVID-19 vaccination ≥ 3, n (%) | 290 (71) | 213 (77) | 77 (59) | <.0001 |
| Household annual income (million yen), n (%) | ||||
| <2 | 17 (4) | 10 (4) | 7 (5) | |
| 2–3.99 | 36 (9) | 20 (7) | 16 (12) | |
| 4–7.99 | 77 (19) | 49 (18) | 28 (21) | |
| ≥8 | 88 (22) | 73 (27) | 15 (11) | |
| Unknown | 188 (46) | 123 (45) | 65 (50) | |
| Sexual history, n (%) | 119 (29) | 87 (32) | 32 (24) | .096 |
| Faculty of Medicineb, n (%) | 144 (35) | 125 (45) | 19 (15) | <.0001 |
| Knowledge about the HPV vaccine, n (%) | ||||
| HPV vaccine | 395 (97) | 273 (99) | 122 (93) | .0004 |
| Catch-up vaccination | 231 (57) | 187 (68) | 44 (34) | <.0001 |
| Free vaccinationc | 327 (81) | 256 (93) | 71 (54) | <.0001 |
| Routine vaccination | 262 (65) | 225 (82) | 37 (28) | <.0001 |
| Obligation to make efforts to receive vaccination | 217 (53) | 186 (68) | 31 (24) | <.0001 |
| Approaching deadline for free catch-up vaccination | 225 (55) | 180 (65) | 45 (34) | <.0001 |
| Prevention of diseases other than cervical cancer | 159 (39) | 126 (46) | 33 (25) | <.0001 |
| Preventive effectiveness even after sexual debut | 155 (38) | 119 (43) | 36 (27) | .0022 |
| Availability of vaccination for men | 136 (33) | 115 (42) | 21 (16) | <.0001 |
| Benefits of vaccination for men | 146 (36) | 122 (44) | 24 (18) | <.0001 |
| No causal relationship with the media-reported serious adverse events | 87 (21) | 80 (29) | 7 (5) | <.0001 |
| Attitudes toward the HPV vaccine, n (%) | ||||
| Anxiety | 161 (40) | 84 (31) | 77 (59) | <.0001 |
| Belief that everyone should be vaccinated | 200 (49) | 174 (63) | 26 (20) | <.0001 |
IQR; interquartile range, HPV; human papillomavirus.
aNon-acceptance group includes hesitancy and refusal.
bFaculty of Medicine includes Department of Medicine and Department of Nursing.
cHPV vaccine was fully covered by public funds.
Reasons for acceptance or non-acceptance
Among the 275 participants in the acceptance group (Figure 2), common reasons for acceptance included perceived effectiveness in preventing cervical cancer (n = 224, 81%), availability of free vaccination (n = 174, 63%), and parental recommendation (n = 127, 46%). Among the 131 participants in the non-acceptance group (Figure 3), common reasons for non-acceptance were insufficient knowledge about the HPV vaccine (n = 63, 48%), concerns about adverse events (n = 57, 44%), and lack of awareness of where to receive vaccination (n = 45, 34%).
Figure 2.
Reasons for receiving HPV vaccination (n = 275).
Multiple responses were permitted for the questions.
Figure 3.
Reasons for HPV vaccine hesitancy or refusal (n = 131).
Multiple responses are obtained for each question. Complicated reimbursement procedures included cases in which the respondent’s residence registration was outside the prefecture. Lack of information included cases in which the vaccination notice was sent to the respondent’s parents’ homes.
Potential factors associated with acceptance
Unadjusted logistic regression analysis showed that most variables related to background characteristics and knowledge of HPV vaccine, except for sexual history, were significantly associated with HPV vaccine acceptance. For example, enrollment in the Faculty of Medicine (OR: 4.91; 95% CI: 2.86–8.44), awareness of the catch-up vaccination program (OR: 4.20; 95% CI: 2.70–6.54), awareness of the obligation to make efforts to receive vaccination (OR: 6.74; 95% CI: 4.19–10.9), and awareness that the serious adverse events reported in the media have no causal relationship with the vaccine (OR: 7.27; 95% CI: 3.25–16.3), were associated with acceptance. In particular, knowledge about HPV vaccine (OR: 10.1; 95% CI: 2.14–47.3), awareness that the vaccine is provided free of charge (OR: 11.4; 95% CI: 6.38–20.3), and awareness that HPV vaccination is part of the routine immunization program (OR: 11.4; 95% CI: 7.01–19.6) were strongly associated with acceptance.
After adjustment for 13 covariates related to baseline characteristics, knowledge, and attitudes toward HPV vaccination (see Methods), multivariable logistic regression analysis identified that knowledge about free vaccination (adjusted OR: 3.86; 95% CI: 1.65–9.06), routine vaccination (aOR: 5.72; 95% CI: 2.71–12.1), and the obligation to make efforts to receive vaccination (aOR: 2.21; 95% CI: 1.13–4.35) were independently associated with acceptance of HPV vaccine (Figure 4). Participants who believed that everyone should be vaccinated were more likely to accept HPV vaccination (aOR: 5.46; 95% CI: 2.59–11.5), whereas anxiety toward HPV vaccine was associated with low acceptance (aOR: 0.37; 95% CI: 0.19–0.71). Sensitivity analysis comparing HPV-vaccinated participants with all others yielded similar findings. Additionally, Faculty of Medicine enrollment (aOR: 2.24; 95% CI: 1.21–4.17) and knowledge about catch-up vaccination (aOR: 0.36; 95% CI: 0.16–0.80) were identified as independent predictors (Supplementary Figure S1).
Figure 4.
Factors associated with acceptance of HPV vaccine: multivariable logistic regression.
Multivariable logistic regression analysis identified that knowledge about fee vaccination, routine vaccination, and obligation to receive vaccination were independently associated with acceptance of the HPV vaccine. Anxiety regarding the HPV vaccine was negatively associated with acceptance. Confidence interval, CI.
Discussion
In this study, HPV vaccination behavior was assessed among the catch-up generation, and factors associated with acceptance of HPV vaccine were evaluated. Adequate knowledge about the HPV vaccination program – particularly the system and costs – was positively associated with HPV vaccine uptake. In addition, anxiety toward HPV vaccine was a suppressive factor for vaccination (aOR: 0.37; 95% CI: 0.19–0.71). These findings suggest that accessible information about the HPV vaccination program regarding its availability and cost, and vaccine-related anxiety may be considered as important targets for further interventional studies aimed at improving HPV vaccination uptake in the target population.
The present study identified three important findings. First, the results provide valuable insights into anxiety as a major barrier to HPV vaccine uptake among Japan’s catch-up generation, a population affected by the vaccine crisis for nearly a decade. A previous online survey targeting this population in Japan revealed that vaccine-hesitant individuals were twice as likely to fear potential HPV vaccine-related adverse events, which is consistent with our findings.11 Similarly, systematic reviews have shown that concerns about vaccine safety are the principal barrier to HPV vaccine acceptance among adolescents and young adults.6,7 In Japan, extensive media coverage of alleged adverse events, together with the rapid dissemination of related concerns through social media, has heightened public anxiety.12 In addition, the suspension of proactive governmental recommendations for HPV vaccine has further undermined confidence in the immunization policy. Consequently, public concern has continued to outweigh scientific evidence, resulting in a prolonged decline in HPV vaccination uptake. To address the HPV vaccine crisis and reduce vaccine-related anxiety, proactive risk communication by authorities and strengthened collaboration among healthcare professionals are urgently needed. Furthermore, given the substantial influence of media on public vaccine attitudes in Japan, leveraging media channels to disseminate clear and evidence-based information about the HPV vaccine may represent a potentially valuable strategy in improving vaccine uptake.
Second, HPV-related knowledge associated with vaccination acceptance was comprehensively assessed by categorizing it into vaccination systems, cost, and efficacy. Acceptance rates differed across faculties, with the highest acceptance rate observed among medical students. This difference may reflect higher levels of knowledge about HPV and the HPV vaccine, as well as greater health literacy, a finding supported by several previous reports.8,9 Moreover, awareness of the catch-up vaccination program, free vaccination, and vaccine obligation – rather than detailed knowledge of vaccine efficacy – were independent factors associated with HPV vaccine uptake. Consistent with these findings, a systematic review conducted in Europe showed generational differences in factors related to HPV vaccine hesitancy: information-related issues were more frequently cited among young adults than among adolescents, whereas concerns about vaccine effectiveness were less common among young adults.7 In Japan’s catch-up vaccination program, HPV vaccination was administered predominantly at medical institutes rather than through school-based mass vaccination. Given that HPV vaccination in Japan relies on individual decision-making and clinic-based delivery, more targeted intervention strategies are required. The present findings suggest that providing straightforward information regarding the vaccination system and cost may be more influential for HPV vaccine uptake than providing detailed scientific knowledge about HPV vaccine.
Third, the present study provides informative findings suggesting that parental influence on HPV vaccination behavior appears to persist even into young adulthood. Although parental recommendations and intentions are well known to affect HPV vaccination behavior among adolescents,13–15 little is known about their impact among young adults. In this study, parental recommendation was one of the most common reasons for HPV vaccine acceptance among young adults (46%). These findings indicate that, even in young adults, parent-targeted interventions remain important alongside direct education of the target population. Previous studies have shown that the most common reason for HPV vaccine hesitancy among parents was concern about vaccine safety.6,7 Given the evidence that physician recommendations directly influence parental decision-making and contribute to increased vaccination uptake,16,17 physician-led interventions directed at parents are crucial. A large-scale study showed that public confidence in vaccines in Japan – regarding their importance, safety, and effectiveness – was the lowest in the world.18 In this context of low confidence, greater and multifaceted efforts are required to build vaccine trust in Japan.
The present study has several limitations. First, this was a single-center study targeting university students; therefore, the generalizability of our findings to the broader catch-up population remains uncertain. Previous studies have shown that higher educational attainment and student status are associated with greater acceptance of HPV vaccination in this generation.10,11 However, by stratifying participants into acceptance and non-acceptance groups and simultaneously evaluating both knowledge and anxiety, the present study suggests that latent anxiety remains the primary driver of vaccine hesitancy, even in highly educated populations. Second, the overall response rate was low (9.6%), and the secondary response rate among female students was 16.5%, indicating that the study is subject to response bias and self-selection bias. Medical and nursing students accounted for 35% of respondents, and their over-representation may have inflated the first-dose coverage rate observed in this study (48%) compared to that reported for the population-level catch-up generation in Japan at the time of the study (9.1–31.6%).19 Consistent with this, the sensitivity analysis identified enrollment in the Faculty of Medicine as an independent factor associated with having already received HPV vaccination. These factors may have introduced bias into the predictor estimates derived from multivariable analyses. Specifically, the associations between knowledge-related factors and acceptance may be overestimated, whereas the suppressive effect of vaccine-related anxiety on acceptance may be underestimated. Nevertheless, a reasonably sized non-acceptance group was enrolled, which allowed multivariable analyses to be conducted. Notably, the findings suggest that, in this population, straightforward information regarding the vaccination system and cost may be more influential in promoting HPV vaccine uptake than detailed scientific knowledge about HPV infection or vaccine efficacy. Third, vaccination status and scheduling were based solely on self-report without objective verification, which may introduce social desirability and recall bias. However, the anonymous nature of the survey was intended to minimize social desirability bias, and the relatively recent implementation of the catch-up vaccination program in Japan may have reduced the likelihood of recall bias. Fourth, given the large number of knowledge and attitude variables examined in the univariable and multivariable analyses, the possibility of false-positive findings cannot be excluded. No correction for multiple comparisons, such as Bonferroni correction or false discovery rate adjustment, was applied. This should be considered when interpreting the results. Fifth, cervical cancer screening behaviors, including screening intention and uptake, were not assessed. From the perspective of cervical cancer elimination, it is essential to emphasize not only HPV vaccination but also the importance of cervical cancer screening. Further studies focusing on the catch-up generation are warranted in light of these considerations. Finally, this study was limited to female students, and whether similar findings would be observed in males remains unclear. Vaccination against HPV in males is expected to provide indirect protection for females through herd immunity as well as direct protection against condyloma acuminata, oropharyngeal cancer, anal cancer, penile cancer, and reduced sperm count.20–24 Therefore, evaluating HPV vaccine acceptance among males of the catch-up generation could yield valuable insights in guiding future vaccination efforts.
In conclusion, in the catch-up generation, acquiring basic knowledge about the HPV vaccination program was identified as a factor associated with vaccine acceptance, whereas anxiety toward HPV vaccine constituted a major barrier to vaccination. Parental recommendation was among the most commonly reported reasons for vaccination, suggesting that parental perspectives may still influence vaccination decisions even in young adulthood. These findings highlight the need for further evaluation in interventional studies aimed at promoting HPV vaccine uptake among so-called vaccine-crisis generation.
Supplementary Material
Acknowledgments
We would like to thank all students who participated in this survey and the faculty members who supported the distribution of the online questionnaire.
Biography
Takashi Matono is an Associate Professor at Saga University Hospital, specializing in infectious diseases, clinical microbiology, tropical medicine, travel medicine, and vaccines for infectious diseases.
Funding Statement
The author(s) reported there is no funding associated with the work featured in this article.
Disclosure statement
TM has received speaker honoraria from Pfizer, Meiji Seika Pharma, GSK, MSD, Gilead Sciences, and Daiichi Sankyo. MH received speaker honoraria from Sanofi, Pfizer Japan, Meiji Seika Pharma, and Moderna Japan. The other authors have no conflicts of interest to declare.
We used Claude for English-language editing and proofreading of the manuscript. No AI tools were used to generate original scientific content or write portions of the manuscript. Authors take full responsibility for the final content.
Data availability statement
The data supporting this study are available from the corresponding author upon reasonable request.
Supplemental material
Supplemental data for this article can be accessed online at https://doi.org/10.1080/21645515.2026.2697396.
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Supplementary Materials
Data Availability Statement
The data supporting this study are available from the corresponding author upon reasonable request.