Knowledge and Awareness of Human Papillomavirus Vaccination and Cervical Cancer among Men and Women in Japan: A Questionnaire Survey

Background: In many advanced countries other than Japan, the incidence and mortality rates of cervical cancer, which is mainly caused by the human papillomavirus (HPV) infection, are decreasing probably due to the high rate of HPV vaccination and cervical cancer screening. In Japan, these rates are on the rise owing to the stagnation of vaccination and low screening rate. To improve these situations, active promotion of HPV vaccination and screening is required. As a preliminary stage, we investigated perceptions regarding cervical cancer and HPV vaccines among Japanese men and women and examined the difference in perceptions by sex. Methods: This was a prospective cross-sectional questionnaire survey targeting Sojo University students and working adults. University students were targeted before learning about cervical cancer. Working adults were recruited on the basis of information from the Health Promotion of Health and Welfare Department of Kumamoto Prefectural Government in Japan and from companies via student organizations promoting cancer prevention. We surveyed respondents’ knowledge and awareness about HPV vaccination and cervical cancer and performed logistic regression analysis to compare the results between men and women. Result: A total of 557 completed questionnaires (205 men and 352 women) were analyzed. Women had high levels of knowledge and awareness about HPV vaccination and cervical cancer compared with men. However, 70% of women surveyed had never been screened for cervical cancer. Conclusion: A total of 557 completed questionnaires (205 men and 352 women) were analyzed. Women had high levels of knowledge and awareness about HPV vaccination and cervical cancer compared with men. However, among surveyed women, the degree of knowledge and awareness was lower than that among women in other countries with established HPV vaccination programs. Furthermore, 70% of women surveyed had never been screened for cervical cancer.

The situation regarding HPV vaccination against cervical cancer is quite different in Japan, the only advanced country with high rates of cervical cancer morbidity and mortality (Katanoda et al., 2021) at 10,978 new cases and 2,921 deaths per year (ganjoho.jp). In Japan, HPV vaccination started in 2010, and HPV vaccine was included in the routine immunization program under the Preventive Vaccination Law in April 2013 (Ministry of Health, 2013b). However, owing to reports of adverse reactions such as pain and movement disorders for which a causal relationship with vaccination could not be ruled out, the Ministry of Health, Labour and Welfare announced in June 2013 that routine HPV vaccination would not be actively recommended (Ministry of Health, 2013a). As a result, the vaccination rate abruptly dropped from 70% to 1.6% among young teens (Nakagawa et al., 2020), a situation that continued for nearly 9 years. On the basis of a recent report (Falcaro et al., 2021), the Ministry of Health, Labour and Welfare finally decided to resume active recommendation of HPV vaccination from April 2022 (72nd Health Sciences Council, 2021; Ministry of Health, 2021). Thus, vaccination coverage is expected to improve in the future. In keeping with the vaccination rate, the rate of regular gynecologic examination for screening of cervical cancer in Japan is the lowest among Group of Seven (G7) countries, at 43.7%. In contrast, these rates in the remaining G7 countries are approximately 70%-80% (OECD, 2022). Therefore, Japan must also improve the rate of consultation and cervical cancer screening. The World Health Organization (WHO) has announced a strategy to accelerate the elimination of cervical cancer (World Health Organization, 2020). WHO declaration sets out three objectives: raise the HPV vaccination rate to 90% for girls by 15 years of age, increase the screening rate to 70% for women by age 35 years and again by age 45 years, and treat 90% of women identified with cervical disease.
Under these objectives, it is necessary to actively increase the rates of vaccination and periodic screening in Japan. For this, gynecologic examination among women should be promoted. Therefore, it is important to inform the public in Japan regarding the characteristics of cervical cancer and HPV as a trigger for consultation. In this regard, few surveys have reported on the current perceptions of cervical cancer and HPV in Japan (Oshima and Maezawa, 2013;Sukegawa et al., 2021). Additionally, existing reports have only targeted women because cervical cancer is a disease unique to women; thus, men's perceptions of cervical cancer and HPV are unknown, unlike in other countries (Baer et al., 2000;Kops et al., 2019). To raise awareness regarding cervical cancer and HPV throughout Japanese society, men's active involvement is essential. In this study, we conducted a survey on the perceptions of cervical cancer and HPV among men and women in Japan and examined differences in perceptions by sex.

Participants
This was a prospective observational study. We administered a questionnaire survey from April 2017 to November 2017. Questionnaires were provided in printed form. Participants were first-, second-, and third-year pharmacy students at Sojo University and employees at three companies in Kumamoto City (Meikougijuku, Kumamoto Prefectural Television Corporation, and Nippon Life Insurance Company) in Japan. Regarding recruitment of companies to include in this study, we received a list of companies that would be willing to cooperate in administering the survey from the Health Promotion of Health and Welfare Department of Kumamoto Prefectural Government. We communicated with each company individually by telephone, email, or in person, and we received permission from employers for workers to cooperate in filling out the questionnaire. Otherwise, we recruited companies via student organizations that promoted the importance of cancer prevention. Pharmacy students at Sojo University receive academic lectures about cervical cancer in their third year. To avoid the influence of information regarding HPV and cervical cancer provided in these lectures, we administered the questionnaire survey for third-year pharmacy students in May, before they had received lectures related to cervical cancer. We did not include fourth-, fifth-, and sixth-year pharmacy students in this study because they had already received academic lectures concerning cervical cancer.

Questionnaire items
Eight pharmacy students, three doctors, including an obstetrician-gynecologist, a pharmacist, a cervical cancer survivor, and a person from a television station who was responsible for media programming, participated in the development of the questionnaire. The questionnaire was designed using the Delphi method (Felicity Hasson BA MSc, 2000), in which multiple people repeatedly discussed, verified, reconstructed, and aggregated the results. The questionnaire included items querying respondents' knowledge and awareness about screening and related to cervical cancer.

Statistical analysis
The sample size for the survey was determined considering the number of pharmacy students at Sojo University and the number of employees. We collected 602 completed questionnaires. We excluded surveys from four people who did not give their consent, surveys from another four people who did not provide information regarding their sex, and 37 university students who worked part time at one of the targeted companies. Finally, responses from 557 completed questionnaires were analyzed. For categorical variables, we performed

Participant characteristics
We analyzed the survey responses of 205 men and 352 women. Among men, 143 were university students and 62 were working adults; among women, 213 were university students and 139 were working adults. Approximately 75% of respondents were in their late teens or 20s, and half of all respondents had someone close to them who had had cancer (Table 1).

Knowledge and awareness of cervical cancer
More women than men had correct knowledge and high levels of awareness for the following items: the difference between cervical and uterine body cancer (Q1; OR=0.64, 95% confidence interval [CI]: 0.42-0.99, p=0.044), the degree of knowledge about cervical cancer a pairwise Fisher's exact test. We performed multivariate logistic regression analysis to discriminate responses from women and men for objective variables. Explanatory variables included each questionnaire item with covariates of age, type of occupation (first-, second-, or third-year student or working adult), and presence or absence of a close relationship with a person who has cancer. This multiple logistic regression analysis based on women was individually performed for each question item, and the odds ratio (OR) of each item was estimated. There were fewer than 5% missing values, so we performed a complete case analysis using logistic regression analysis (Patrick Royston, 2009). Each of the analyses was assumed to be independent. All analyses were performed using R version 4. In Q2, degree of knowledge about cervical cancer ("Nothing," "Some," "A little," "A lot") was replaced by dummy variables ("0," "1," "2," "3") that were used for continuous variables. In Q16 and Q17, the response option of "Other" was the summed responses of "Can't say" and "No." In these questions, "Yes" was replaced by dummy variable "1," and "Other" was replaced by dummy variable "0". In other questions, "Yes" or "Correct answer" was replaced by dummy variable "1," and "No" or "Incorrect answer" was replaced by dummy variable "0"; The decimal point is rounded to the third place and displayed to the second decimal place; OR, odds ratio; CI, confidence interval; *Maximum likelihood estimation could not be calculated because of quasi-complete separation. For the question regarding having received education about cervical cancer, 47.1% of women responded "yes" compared with 31.7% of men (Q3; OR=0.50, 95% CI: 0.32-0.77, p=0.002). However, more than 70% of respondents did not know the causes of cervical cancer, regardless of sex (Table 2, 3).

Discussion
In this study, we administered a questionnaire survey to university pharmacy students and adult workers, and compared knowledge and awareness about cervical cancer between men and women in Japan. Men had less knowledge and awareness of cervical cancer than women. Additionally, men had lower knowledge levels regarding HPV vaccination. Moreover, our results showed that men were less willing than women to obtain information about cervical cancer. Because many believe that cervical cancer is a female-specific disease, men may think that the disease is not relevant to them and thus have little interest. However, HPV affects both men and women (Chesson et al., 2014). For example, HPV causes genital warts, oropharyngeal cancer, penile cancer, and anal cancer. HPV vaccination for men has been reported to not only inhibit the spread of HPV infection with sexual contact but also prevent HPV-related diseases    (Spînu et al., 2021). Therefore, several countries such as Australia recommend HPV vaccination for men to achieve eradication of cervical cancer and HPV-related diseases (Hall et al., 2019;Laserson et al., 2020). In the case of Japan, HPV vaccination for men was covered by the National Health Insurance as of 2020 (MSD, 2021). However, as described, men had low interest and knowledge levels regarding cervical cancer and HPV vaccines. Our research also revealed that the proportion of men who had received education regarding cervical cancer was low in comparison to women. Low awareness and few educational opportunities among men may reflect the influence of the prolonged period during which HPV vaccination was not actively recommended in Japan, which is a serious problem. If men do not know that the main cause of cervical cancer is HPV and that the virus can be transmitted by both men and women, they will not be able to understand the importance of HPV vaccination. This lack of understanding about HPV and HPV-related diseases can be a barrier to the uptake of HPV vaccination. Thus, it is important that Japanese men as well as women have an opportunity to acquire correct knowledge about HPV and cervical cancer. For instance, in the United States and Canada, educational interventions using computers, pamphlets, and videos on HPV were found to improve university students' knowledge about HPV and their willingness to be vaccinated against HPV (Doherty and Low, 2008;Krawczyk et al., 2012). Additionally, an educational intervention targeting young adults and parents with daughters improved their knowledge and awareness regarding HPV and vaccination (Dempsey et al., 2006;Kennedy et al., 2011;Kester et al., 2014). Such educational support may be effective among Japanese university students and parents, in the long run, which may lead to improvement perceptions about HPV and related diseases among both men and women.
In the case of women specifically, although their knowledge and awareness about cervical cancer were greater than the levels among men, they were low compared with women in other countries that have established HPV vaccination programs (Marlow et al., 2013). Moreover, the proportion of our female respondents who had previously undergone screening for cervical cancer was approximately 30%. This rate is also very low compared with other advanced countries (OECD, 2022). As in men, the reason for these results might have to do with the prolonged period during which HPV vaccination was not actively recommended in Japan, which could have affected both sexes. In this regard, women who had undergone cervical cancer screening understood the importance of cervical cancer screening, and most had a positive attitude about repeated screening for cervical cancer.
Our findings suggest that a key for improving cervical cancer screening in Japanese women is to increase opportunities for a first screening. For this, it is important to further promote education regarding HPV and cervical cancer among women as well as men (Baer et al., 2000;Dempsey et al., 2006;Krawczyk et al., 2012;Kops et al., 2019). However, studies have reported that raising awareness about cervical cancer alone does not lead to actual behavioral changes in women, such as receiving preventive vaccination (Gottvall et al., 2010;Patel et al., 2012;Vanderpool et al., 2013). Thus, additional approaches for changing behavior are needed. A woman's family or partner may play a large role in women's positive attitudes toward screening, as has been reported for some diseases (e.g., cardiovascular health and cancer) (Bevan and Pecchioni, 2008;Vedanthan et al., 2016). Cao et al. stated that life partners influence whether a person receives preventive health care services, and women in particular are more likely to respond to their partner's positive health behaviors (Cao et al., 2020). Our study revealed that women were more likely than men to talk with someone about cervical cancer. Nevertheless, the proportion of women who said that they would inform their partner if they underwent screening and who wanted support from their partner was only 53.2% and 30.4%, respectively. These results are markedly lower compared with those of men (Q16: 89.2%, Q17: 90.2%). As to the reasons for not communicating with their partner, many women thought it was their own problem or a disease specific to women. Thus, women themselves may believe that cervical cancer is a disease specific to women. Another reason reported by some women was a belief that their partner would not understand or sympathize. Therefore, men need to  The response options for Q17 among women were only "Yes" or "No." The reasons for answering "No" to Q16 are shown as bar graphs (multiple answers are acceptable).
have sufficient knowledge regarding HPV and cervical cancer to be empathetic toward their partners. If men had adequate understanding, it is highly likely that they would perceive HPV and related diseases as their own problem. Accordingly, women would more easily trust and could more easily communicate with partners. Women also need to recognize the existence of HPV-related diseases in men and understand that men may be willing to support them. To foster mutual understanding, men and women can discuss topics related to HPV or cervical cancer. Such collaboration would help to increase the proportion of individuals who are vaccinated against HPV and regularly screened for cervical cancer, which would decrease the incidence and mortality of cervical cancer in Japan.
This study had several limitations. First, we performed our survey in a medium-sized city (Kumamoto) of Japan. Second, a limited number of companies cooperated with the survey, resulting in a small sample size. However, our study included a sample of younger male college students, which is unique and valuable in Japan. Moreover, the goal of cervical cancer eradication is being pursued globally, and we believe that the findings of our study can contribute to the development of measures for eradication in Japan. Third, our study was conducted during the period when publicly funded vaccination had been suspended in Japan. Thus, because the Japanese Ministry of Health, Labour and Welfare did not resume its recommendation for vaccination against cervical cancer until April 2022, it is highly likely that current perceptions among young people in Japan are still similar to the prevailing perceptions during the period of our study. Therefore, our findings can be used as baseline data regarding young people's knowledge and awareness about cervical cancer and HPV for surveys that are conducted after publicly funded HPV vaccination resumed in Japan.
In this study, we found that men's awareness about cervical cancer and HPV vaccines was lower than that of women. HPV-related diseases such as cervical cancer do not only affect women. To eradicate cervical cancer, it is important to raise awareness about cervical cancer among men as well as women. Although women's awareness of cervical cancer was higher than that of men in our study, it was lower than the level among women in other countries with established vaccination programs. Therefore, it is also important to raise awareness about HPV and HPV-related diseases among women in Japan. To trigger actions such as cervical cancer screening and vaccination, communication between men and women to foster mutual understanding and concern for health is key.