Factors Related to Satisfaction with Decision-making Regarding Human Papillomavirus Vaccination Behavior among Female University Students in Japan

Introduction: Cervical cancer is the fourth most common cancer among women worldwide. Most cervical cancers are caused by persistent infection with human papillomavirus (HPV) acquired through sexual contact. Decision-making is the process of choosing among several options, and a better decision is one that the people engaged in the decision-making process express satisfaction with. Despite that HPV infection is associated with sexual behavior, no studies in Japan on HPV vaccination decision-making that include perspectives on sexuality exist. This study aimed to determine the factors that influence satisfaction with decision-making concerning HPV vaccination among female university students in Japan. Methods: The cross-sectional study was carried out by an anonymous self-administered questionnaire mail survey of 1988 female university students in Japan between April and July 2021. Of them, 301 agreed to participate in the survey. After the exclusion of those with missing data, the analysis included 252 (12.7%) students. We summarized descriptive statistics in terms of characteristics, satisfaction with decision-making regarding HPV vaccination, HPV vaccination behavior, knowledge, attitude about HPV vaccination, influencing factors, and perceptions and behaviors related to sexuality. Furthermore, we conducted multivariate analyses to investigate factors that influence satisfaction with decision-making regarding HPV vaccination. Results: Of the 252 participants, 102 (40.5%) were satisfied with their decisions regarding HPV vaccination. After adjustment for confounding factors, the multivariable-adjusted odds ratios (95% confidence intervals) for factors associated with satisfaction in decision-making regarding HPV vaccination were as follows: being vaccinated (vs. non-vaccinated) 5.46 (2.51-11.89), having high knowledge scores (vs. per 1 point) 1.09 (1.01-1.17), and having awareness about the risk of contracting sexually transmitted infections (STIs) via sexual intercourse (vs. per 1 point) 0.83 (0.72-0.96). Conclusions: Being vaccinated, having higher knowledge scores, and having lower awareness regarding the risk of STIs were associated with satisfied decision-making concerning HPV vaccination. Providing younger people with correct information about cervical cancer, HPV vaccines, and STI prevention contributes to increased satisfaction with their HPV vaccination decisions.


Introduction
Cervical cancer is the fourth most common cancer among women worldwide (1) .Most cervical cancers are caused by persistent infection with human papillomavirus (HPV) acquired through sexual contact, and most people are infected with HPV shortly after the onset of sexual activity (1), (2) .HPV vaccines work best if administered before HPV exposure.For this reason, vaccination before the initiation of sexual intercourse is recommended globally, and the World Health Organization (WHO) also recommends vaccinating girls aged 9-14 years, when most have not started sexual activity (1) .
The HPV vaccine was approved by the Japanese government in October 2009 and became available for use at medical institutions in December of the same year.Moreover, in April 2013, public funding was provided for HPV vaccines, target-ing the population from the sixth grade of elementary school to the first grade of high school (approximately ages 11-16) as a project to promote emergency measures for vaccination against cervical cancer (3) .Nevertheless, because of the issue of adverse reactions, the Japanese government withheld vaccination recommendations after only 3 months of this program, and there was no active recommendation made from June 2013 to March 2022 (3), (4), (5) .Japanese media reported these adverse reactions sensationally, resulting in widespread misinformation and misunderstanding of the HPV vaccine, and distrust of the HPV vaccine persists among most Japanese people (6) .As a result, HPV vaccination rates remain low in Japan, reported to be 1.9% in 2019 (4) .
Decision-making is the process of choosing among several options, and a better decision is one that the people engaged in the decision-making process express satisfaction with (7) .Previous studies have shown that the HPV vaccination group has a higher rate of satisfaction with decision-making (8) and with sexual behavior.There have been conflicting reports regarding the association between HPV vaccination and an earlier age of first sexual intercourse and the number of sex partners, with some studies (8), (9) that state that there is an association and others that report that there is no association (10) .Unlike other diseases that cause airborne or droplet transmission, the risk of HPV infection in Japan varies greatly depending on the nature of sexual activity.Sexual activity is the most private domain of each individual, and vaccination decisions should be made after careful consideration based on one's own values about sex.The sexual intercourse experience rate of female students in Japan (2019) has been reported to be 19.3% for high-school students and 36.7% for university students (11) .In this way, university students become more familiar with the issue of sexuality by becoming more sexually active as indicated by these higher rates.Despite HPV infection being associated with sexual behavior, no studies of HPV vaccination decisionmaking in Japan include perspectives on sexuality such as sexual intercourse experience or awareness of the risks of getting pregnant or contracting STIs.
Clarifying the factors that are related to satisfaction with decision-making regarding HPV vaccination among female university students in Japan could be useful for determining appropriate interventions to enhance satisfaction with these decisions.Although previous studies have shown that knowledge about HPV and HPV vaccination, as well as attitudes toward HPV vaccination (12) , are related to decision-making regarding HPV vaccination, the association between perspectives on sexuality and satisfaction with decision-making in terms of HPV vaccination has not yet been assessed.Thus, this study aimed to determine the factors that influence HPV vaccination behaviors, specifically including perspectives on sexuality, and how they relate to satisfaction with decisionmaking regarding HPV vaccination among female university students in Japan.

Study participants and procedure
This anonymous self-administered questionnaire mail survey was conducted from April to July 2021.The targeted list of National Councils of Nursing universities in Japan was randomly ranked, and a request for research permission was sent to the deans of those universities.The universities that gave permission for this research were selected as the research target universities.Requests were repeated until the number of research participants reached approximately 1,000 students.Non-nursing universities were randomly ranked from the list of universities on the Ministry of Education, Culture, Sports, Science and Technology website and selected in order from the top of the list.In doing so, medical-related programs (medical, pharmacy, and others) were excluded.Requests for research permission were sent to the deans of the faculties of each university, and approximately 1,000 research participants were selected via the same method as from nursing universities.Finally, we distributed anonymous self-administered questionnaires to 1,089 nursing and 899 non-nursing university female students (1,988 students overall).Of these, 301 female university students agreed to participate in the mail survey.We excluded those with missing data.A total of 252 (12.7%) female university students were included in the analysis.
The study protocol was written following the Declaration of Helsinki and was approved by the Institutional Review Boards of Osaka Prefecture University (date of approval: March 25, 2021; approval code: 2020-51).Informed consent was obtained from all participants who were included in the study.

Outcome
Study participants were classified into two groups according to their satisfaction with HPV vaccination behavior: the satisfied group and the unsatisfied group.Those who selected "I was satisfied with my HPV vaccination behavior" were classified as the satisfied group, and those who selected "I was not satisfied with my vaccination behavior" or "I could not say either way" were classified as the unsatisfied group.

Exposure factors and potential confounding factors
Factors obtained via a self-administered questionnaire included the following: age, university department (nursing or nonnursing), HPV vaccination behavior (vaccinated or non-vaccinated), and number of vaccinations (once, twice, or thrice).
Regarding HPV vaccination behavior, study participants were classified into a vaccinated group and a non-vaccinated group.Those who selected "I received HPV vaccination at least once" were classified as the vaccinated group, and those who selected "I have never been HPV vaccinated" were classified as the non-vaccinated group.
In terms of knowledge of cervical cancer, HPV, and HPV vaccination, participants were asked a total of 20 items concerning cervical cancer, HPV, and HPV vaccination.The respondents were asked whether they knew or did not know about each item, and the number of items they knew was used as their knowledge score (range: 0-20).
Attitudes toward HPV vaccination were measured using the attitudes scale for HPV vaccinations (13) .This scale consists of 29 items divided into eight subscales.Items were scored on a five-point Likert scale ranging from 1 (strongly disagree) to 5 (strongly agree), with higher scores indicating higher attitudes toward each sub-scale.The subscales were (1) family health awareness, (2) contact with vaccination topics, (3) ability to adjust to vaccination, (4) threat of cervical cancer, (5) high affirmation and interest regarding vaccination, (6) negative attitude/difficulty regarding vaccination, (7) anxiety about vaccines, and (8) barriers to vaccination time and cost.The reliability and validity of this scale have been previously confirmed (14)   .
Regarding perceptions related to sexuality, the following three items were asked.The VAS (visual analog scale) was used to ask about the possibility of getting pregnant via sexual intercourse, the possibility of contracting STIs via sexual intercourse, and the possibility of contracting cervical cancer via sexual intercourse.Participants were also asked about their sexual intercourse experience (presence or absence).
Moreover, participants were asked to respond (yes/no) whether each of the following was an influencing factor for their HPV vaccination behavior: parental recommendation, healthcare provider's recommendation, schoolteacher's recommendation, sexual education, vaccination of friends, cost of vaccination, problems with adverse reactions, and free coupon.

Statistical analysis
Differences in age, university department, knowledge, attitude, and perceptions and behaviors related to sexuality between the groups satisfied and unsatisfied with their HPV vaccination behavior were determined via t-tests for continuous data of normal distribution.Dichotomous and categorical data were analyzed using the chi-squared test and are shown as percentages.
Logistic regression models were used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) of each factor (response variable: 1 = satisfied group, 0 = unsatisfied group).Moreover, the multivariable-adjusted ORs and 95% CIs of each factor were calculated in a model including age (continuous variable), HPV vaccination behavior (vaccinated or unvaccinated), university department (nursing or non-nursing), knowledge scores (continuous variable), attitude of contact with vaccination topics (scores ≥9 or <9), anxiety about vaccines (scores ≥10 or <10), and recognition of possibility of contracting STIs via sexual intercourse (continuous variable: VAS score).The subscales of attitude scale scores were delimit-ed by each median.
Additional analysis of factors that were related to HPV vaccination behaviors was carried out.Differences in age, university department, knowledge, attitude, influence factors, and perceptions and behaviors related to sexuality between the vaccinated and non-vaccinated group with HPV vaccination among Japanese university female students were determined using t-tests for continuous data of normal distribution.Dichotomous and categorical data were analyzed using the chisquared test and are shown as percentages.
Logistic regression models were used to estimate the OR and 95% CI of each factor (response variable: 1 = vaccinated group, 0 = unvaccinated group).Moreover, the multivariableadjusted ORs and 95% CIs of each factor were calculated in a model including age (continuous variable), university department (nursing or non-nursing), knowledge scores (continuous variable), attitude of family health awareness (scores ≥16 or <16), contact with vaccination topics (scores ≥9 or <9), ability to adjust to vaccination (scores ≥16 or <16), high affirmation and interest regarding vaccination (scores ≥14 or <14), anxiety about vaccines (scores ≥10 or <10), barriers to vaccination time and cost (scores ≥10 or <10), and influence factors of parents (yes or no), healthcare provider (yes or no), school teacher (yes or no), problems with adverse reactions (yes or no), free coupon (yes or no), and sexual intercourse experience (presence or absence).The subscales of attitude scale scores were delimited by each median.All data were analyzed using SPSS statistical software (version 27; SPSS Inc, Chicago, IL, USA).All reported p-values were two-tailed, and values of <0.05 were considered statistically significant.

Results
Of the 252 female university students, 102 (40.5%) selected "I was satisfied with my HPV vaccination behavior" (satisfied group), 126 (50.0%) selected "I could not say either way," and 24 (9.5%) selected "I was not satisfied with my vaccination behavior" (unsatisfied group).
The differences in age, university department, knowledge, attitude scale, and perceptions and behaviors related to sexuality between the participants who were satisfied and unsatisfied with their HPV vaccination behavior are shown in Table 1.Of the 252 participants, the mean age was 21.3 years, 46.2% were nursing students, and 42.5% had been vaccinated.Participants who were satisfied with their HPV vaccination behavior included a significantly higher proportion of nursing students (p < 0.001), HPV vaccinated (p < 0.001), attitude of contact with vaccination topics score above the median (p = 0.001), and attitude of anxiety about vaccines below the median (p < 0.001) in comparison to the unsatisfied group.Furthermore, satisfied participants had a significantly higher age (p < 0.001) and knowledge score (p < 0.001) and significantly lower scores of recognition of the possibility of contracting STIs by sexual intercourse (p < 0.049).There were no statisti-cally significant differences in other perceptions and behaviors related to sexuality between the satisfied group and the unsatisfied group.
The univariate and multivariable-adjusted ORs and 95% CIs for the group satisfied with their vaccination behavior are shown in Table 2 Table 3 shows the differences in age, university department, knowledge, attitude scale, influence factors, and perceptions and behaviors related to sexuality between the vaccinated group and the non-vaccinated group.Participants who were vaccinated included a significantly higher proportion of nursing students (p < 0.001), above-median scores for attitude of family health awareness (p = 0.004), attitude of contact with vaccination topics (p < 0.001), attitude of ability to adjust to vaccination (p = 0.004), attitude of high affirmation and interest regarding vaccination (p < 0.001), and below-median scores for attitude of negative attitude/difficulty regarding vaccination (p < 0.001), attitude of anxiety about vaccines (p < 0.001), and attitude of barriers to vaccination time and cost (p < 0.001).In terms of influencing factors, vaccinated partici-pants reported higher influence of parental recommendation (p < 0.001), healthcare provider's recommendation (p = 0.044), schoolteacher's recommendation (p < 0.001), and free coupon (p < 0.001), and lower influencing factors for problems with adverse reactions (p < 0.001).They also reported a higher proportion of sexual intercourse experience (p = 0.011) and had significantly higher age (p < 0.001) and knowledge score (p < 0.001) than the non-vaccinated group.Perceptions related to sexuality between the vaccinated group and the nonvaccinated group were not significantly different.
The univariate and multivariable-adjusted ORs and 95% CIs for factors related to vaccination behavior for the vaccinated group are shown in Table 4.After adjustment for confounding factors, the multivariable-adjusted ORs and 95% CIs for the vaccinated group were 2.36 (1.12-5.00)for age (per 1 year), 3.45 (1.11-10.72)for above-median attitude of contact with vaccination topics, 31.86 (9.81-103.47)for influencing

Discussion
This study clearly shows the factors that are related to satisfaction with decision-making regarding HPV vaccination behavior among female university students in Japan.After adjust- population.Making a well-informed decision that is consistent with personal values is important (7) .In Japan, the need to make appropriate decisions and behavioral choices according to scientific thinking and correct judgment on health-related issues is discussed in school education curricula (15) .Subject-centered decision-making must presuppose an understanding of the benefits and disadvantages of individual options and allow for free judgment based on one's own values.Because HPV is transmitted through sexual behavior, decision-making regarding HPV vaccination requires a perspective on sexuality and the provision of correct information.Nevertheless, considering that the recommended target population for HPV vaccination is students from the sixth grade of elementary school students to the first grade of high school, it is necessary to target not only the women for intervention but also their parents.
In our study, the rate of satisfaction with decision-making was higher in the vaccinated group, in the group with higher knowledge of HPV and HPV vaccines, and among those with lower recognition of the possibility of contracting STIs via sexual intercourse.The other perceptions and behaviors related to sexuality were not associated with satisfaction with their decision-making regarding HPV vaccination.Nevertheless, parents of the target women may not want to directly address their daughters' sexual behavior and are likely to have negative feelings about it.
Previous studies have reported that parents' HPV vaccination decision-making can be influenced by healthcare providers (16) , and parent satisfaction with provider communication may play an important role in this process.Hence, healthcare providers that offer correct information to mothers and target women will effectively influence decision-making.Moreover, HPV vaccination status was not significantly associated with an increased likelihood of sexual activity, decreased age of sexual debut, or an increased number of sexual partners (10) , and the understanding of the roles of sexual behaviors in HPV transmission requires proper education (17) .Moreover, in our study, satisfaction with decision-making regarding HPV vaccination and HPV vaccination status was not significantly associated with sexual intercourse experience.Therefore, concerns regarding the influence of the HPV vaccine on sexual behavior are likely unfounded for both men and women.Healthcare providers should use the results of these studies to provide correct information to parents and target women, including the perspective of sexuality.
Globally, HPV vaccination is recommended for women aged 9-14 years (1) , when most have not initiated sexual activity.However, women of this age may not make their own HPV vaccination decisions, especially those that consider perspectives that are related to sexuality.Furthermore, parental consent is required for HPV vaccination for minors in Japan.Previous studies have revealed a relationship between vaccination and parental influence (9), (18) .In our study, parental recommen-dation was a major factor that influences HPV vaccination, and problems with adverse reactions and free coupons also influenced HPV vaccination behaviors.Previous studies reported included the cost of vaccines, lack of knowledge, and perception that they were at low risk as reasons for not being vaccinated (19) , similar to the results of our study.Higher levels of knowledge of cervical cancer, HPV, the HPV vaccine, and STIs influence HPV vaccination behavior (20), (21) .Additionally, many of those who refused HPV vaccination doubted the safety and efficacy of the new vaccine or perceived themselves as not at risk of HPV infection (20) .These findings suggest that providing information and knowledge regarding the etiology of cervical cancer and its link to HPV is an essential component of enhancing HPV vaccination behaviors.
Although vaccination recommendations from healthcare providers are a very important intervention, in our study, these were not associated with HPV vaccination.The Japanese government had previously suspended HPV vaccination recommendations, and healthcare providers may not have been able to explain the vaccination recommendations to eligible target women and their parents.Nevertheless, since the resumption of recommended HPV vaccinations in April 2022, it has become necessary for healthcare providers to provide high-quality information and correct knowledge.A previous study also reported that receiving quality explanations from healthcare providers and being satisfied with the explanations and communication from healthcare providers were significant influences on HPV vaccination, and recommendations from healthcare providers were also a major influencing factor (18) .The results of our study indicate the importance of communicating correct information and knowledge regarding cervical cancer, HPV, HPV vaccine, and STIs to parents as well as to the target women for vaccination and decision satisfaction.It is also clear that HPV vaccination should be free.
Based on our study, HPV vaccine-related sexual education in schools, especially from healthcare providers, is an important intervention because the targets of this vaccination program are from the sixth grade of elementary school to the first grade of high school.In implementing this, healthcare providers should go to schools to provide high-quality, accurate information.Educational materials and program-based interventions for Japanese high-school students have been reported to affect short-term behavioral intentions (22) , and mothers' narrative messages may be persuasive when targeting mothers to promote HPV vaccination (23) .Because HPV is transmitted through sexual behavior, as an aid to decision-making support, perspectives on sexuality should also be accurately communicated to avoid misunderstandings.Intervention with parents (especially mothers) is also necessary.To this end, parents should be allowed to observe during school sexual education, and seminars for parents should be conducted during Parent-Teacher Association (PTA) activities.Additionally, we believe that disseminating high-quality, accurate information via social networking services for women who are not eligible for the recommended vaccination would be effective.Being vaccinated, having higher knowledge scores, and having lower awareness about the risk of STIs were associated with satisfied decision-making concerning HPV vaccination.Providing younger people with correct information about cervical cancer, HPV vaccines, and STI prevention would contribute to increased satisfaction with HPV vaccination and decisionmaking about HPV vaccination.
To our knowledge, this study is the first to examine the factors that include perspectives on sexuality related to satisfaction regarding their decisions regarding HPV vaccination for female university students in Japan.Nevertheless, there are some study limitations.First, the cross-sectional study design precludes any conclusions about the causal nature of the observed associations.Therefore, a prospective study is required to confirm our findings.Second, data were obtained only from female university students who agreed with the study aims and fully completed the questionnaire.Therefore, it is possible that the target population of interest for our study was participating at a higher rate than the general population.This was also likely because the percentage of the vaccinated group was higher than the general vaccination rate (24) for the same age group.The questionnaire was developed by the authors and cannot be said to be sufficiently reliable and valid.Furthermore, the question about the subjects' experience with sexual intercourse may be causing the low response rate.As such, we cannot deny the possibility of selection bias because the response rate was 15.1%.Third, other potential confounding factors that were not considered in this study included living environment and individual personality.Despite these potential limitations, the present findings support the conclusion that providing younger people with correct information about cervical cancer, HPV vaccines, and STI prevention is important in promoting improved decision-making concerning HPV vaccination among female university students in Japan.

Table 1 .
Differences in Characteristics between the Groups of Female Japanese University Students Satisfied and Unsatisfied with Their HPV Vaccination Behavior.The scores of perceptions of possibility of getting pregnant, STIs, cervical cancer by sexual intercourse were evaluated by visual analog scale (VAS).
Dichotomous and categorical data were analyzed using the chi-squared or Fisher's exact test and were shown as %.*Continuous data of normal distribution were analyzed by t-test and are shown as mean ± standard deviation.a Subscales of attitude scale scores were categorized by each median.b

Table 2 .
Factors Related to Satisfaction with HPV Vaccination Behavior among Female Japanese University Students.
*Age (continuous variable), HPV vaccination behavior (vaccinated or non-vaccinated), university department (nursing or non-nursing), knowledge scores (continuous variable), attitude of contact with vaccination topics (scores ≥9 or <9), attitude of anxiety about vaccines (scores ≥10 or <10), perceptions of possibility of contracting STIs by sexual intercourse (continuous variable: VAS score) were included in this model.aSubscales of attitude scale scores were categorized by each median.bThescores of perceptions of possibility of getting pregnant, STIs, cervical cancer by sexual intercourse were evaluated by visual analog scale (VAS).Abbreviations: HPV; human papillomavirus, STIs; sexually transmitted infections, OR; odds ratio, CI; confidence interval.factorsforparental recommendation, 0.06 (0.01-0.24) for influencing factors for problems with adverse reactions, and 4.96(1.11-22.16)forinfluencing factors for free coupon.

Table 3 .
Differences in Characteristics and Factors Influencing HPV Vaccination Decisions between the Vaccinated Group and the Non-Vaccinated Group among Female Japanese University Students.The scores of perceptions of possibility of getting pregnant, STIs, cervical cancer by sexual intercourse were evaluated by visual analog scale (VAS).
a Subscales of attitude scale scores were categorized by each median.b ment for confounding factors, being vaccinated, having higher knowledge scores, and having lower awareness about the risk of STIs were associated with satisfaction with their decision-making in terms of HPV vaccination.Moreover, HPV vaccination behaviors were largely associated with parental recommendations and problems with adverse reaction issues in this

Table 4 .
Factors Related to HPV Vaccination Behavior among Female Japanese University Students.