https://orcid.org/0000-0003-0229-2513
ABSTRACT
Girls born in 2001 became eligible for subsidized HPV vaccination when they reached 12 years old in 2013, but that was the year when the Japanese MHLW suspended its official governmental recommendation for HPV vaccination. Those girls will now reach 20 years of age this year, 2021, and they will become eligible for cervical cancer screening. We report on the effects of an educational intervention with an information sheet about their current unvaccinated defenselessness for HPV and the necessity for early and repeated cervical cancer screening as a way to improve their intention to have that screening and their attitude toward HPV vaccination. Among the educated women, 75.2% had a positive intention toward having cervical cancer screening, 24.8% had a negative intention. Educational intervention can significantly promote the intention of having cervical cancer screening in women who had experienced the suspension of the MHLW’s official recommendation for HPV vaccination. As a result of this simple intervention, they were more likely to think that HPV vaccination was needed for themselves.
Introduction
Japan’s national HPV vaccination program began in 2010; it quickly resulted in the immunization of roughly 70% of all girls in the targeted age group, those aged 13–16. In April of 2013, the scheduling of HPV vaccination for girls aged 12–16 became a national routine. However, in June of 2013, after a small number of highly publicized reports that alleged adverse medical events, including pain and motor disability, had occurred in several young girls following their HPV immunization, the Japanese Ministry of Health, Labor, and Welfare (MHLW) suspended its official recommendation for HPV vaccination. Within months, the rate for newly vaccinated girls plummeted, from approximately 70% of targets in 2012 to almost zero for girls aged 12–13 by the end of 2013.Citation1–4
The effectiveness of HPV vaccination is crystal clear. Our team has reported that the abnormal findings from cervical cancer screening were significantly reduced, from 3.96% in 2010–2013 to 3.01% in 2014–2015.Citation5 The incidence of CIN3 or worse cervical cancer for the previously unvaccinated generation of women, before the vaccines were available, was significantly higher than that for the generation of women vaccinated during this enlightened period.Citation6 The prevalence of onco-strains of HPV 16, 31, and 52 infection rates in the vaccinated group was markedly lower than that in the unvaccinated group, and no one had an HPV 18 or 45 infection in the vaccinated group.Citation7 Similar findings for the effectiveness of HPV vaccination for the protection from invasive cancer were also reported in Sweden.Citation8,Citation9
We have calculated the potential increased future cervical cancer incidence and deaths that will result in Japan from this national policy decision of continued null-recommendation for HPV vaccination. The vaccination rate of women born in 2000 in Japan is estimated to currently be a dismal 14.2%; the increases in future incidence and death are estimated to be 3,651 and 904, respectively. The large increase of risks to women born in 2004 amounts to 12.0 women per day who will now be at higher risk for acquiring cervical cancer in their future, and 3.0 women per day newly at risk for future death from that disease in its progressive form.Citation10
The girls born in 2001, who were 12 years old in 2013 when the MHLW suspended its official recommendation for HPV vaccination, will be 20 this year and will become eligible for cervical cancer screening. The vast majority of these women will be unprotected from HPV by vaccination during their late teens when they will have had sexual relationships and possible frequent HPV exposures. We think that cervical cancer screening should be much more strongly recommended for this and succeeding cohorts of unvaccinated women.Citation11
To accomplish this goal, we report here the effects of an educational intervention with an information sheet about this group’s defenselessness against HPV, the necessity of their seeking cervical cancer screening, and the need to improve their intention to have cervical cancer screening and their attitude toward accepting a belated HPV vaccination.
Methods
On November 16th and 17th of 2020, under Internal Review Board approval, we conducted an online survey of Japanese women listed in an internet survey panel as being 19–20 years old. Informed consent was obtained from all women. We delivered the questionnaire via internet to 26500 women and valid survey answers were obtained from 412 women. Initially, a self-administered questionnaire obtained information from the women on their socio-demographic characteristics, such as their employment status, having had sex or not, civil status, having a child or not, their total household income, and their HPV vaccination status. Half of these women (206, 50%) were given an information sheet to read concerning cervical cancer (sheet-educated). The sheet included information regarding the morbidity caused by cervical cancer, the necessity for cervical cancer screening, and that they were women who grew up during a period of HPV-program recommendation-suspension (). The remaining half (206, 50%) did not get this information sheet (non-educated). Afterward, we quizzed the women in both groups about their knowledge concerning cervical cancer, about their and their family’s cervical cancer screening practices, about having talks with their family about cervical cancer, and their intention toward having cervical cancer screening. To evaluate their attitude about HPV vaccination, we asked the 343 non-vaccinated women in this survey group what they thought regarding whether or not they wished they had been vaccinated.
Table 1. Content of the information sheet
We evaluated their intentions toward having cervical cancer screening and their attitudes about HPV vaccination based on their education status at the time. We also assessed several factors that were likely to influence their intention toward having cervical cancer screening and their attitude about HPV vaccination.
Statistics
Differences between the two groups were calculated by the chi-square test and the logistic regression test for categorical variables using MedCalc version 19. The multivariate logistic proportional hazards model (stepwise method) was used to calculate and select the independent factors for their intention to have cervical cancer screening and attitude about HPV vaccination. The level of statistical significance was set at p = .05.
Results
Characteristics of the internet survey responders
The relevant characteristics of the survey responders are shown in . As expected, no statistically significant differences existed between the characteristics of the randomly divided two groups.
Table 2. Characteristics of the internet survey responders
Health consciousness of the survey responders and her family
About the question regarding their HPV vaccination status, among the sheet-educated women, 35 (17.0%) were positive, 127 (61.7%) were negative, and 44 (21.4%) did not answer the question. Among the non-educated women, 34 (16.6%) were affirmative, 140 (68.0%) were negative, and 21 (15.5%) did not answer.
In reference to having cervical cancer screening, among the sheet-educated women, 24 (11.7%) had a screening history and 182 (88.3%) had never been screened. Among the non-educated women, 37 (18.0%) had a screening and 169 (82.0%) had never been screened.
About having a history of cervical cancer screening for her family members, among the sheet-educated women, 60 (29.1%) had a family history of screening, and 146 (70.9%) had never been screened. Among the non-educated women, 42 (20.4%) had a family screening history and 164 (79.6%) had never been screened.
In reference to a question about having conversations with family members about cervical cancer, among the sheet-educated women, 60 (29.1%) had talked with their families, 111 (53.9%) had not, and 35 (17.0%) did not remember. Among the non-educated women, 80 (38.8%) had talked with their families about cervical cancer, 95 (46.1%) didn’t, and 31 (15.9%) did not remember. No statistically significant differences existed between the two groups (sheet-educated and non-educated) for any of these questions ().
Table 3. Health consciousness of the survey responders and their family
Intention to having cervical cancer screening
In reference to the question regarding their intention toward having cervical cancer screening, among the sheet-educated women, 155 (75.2%) had a positive intention to having cervical cancer screening sometime soon, and 51 (24.8%) had a negative intention. Among the non-educated women, 132 (64.1%) had a positive intention, 38 (18.4%) were negative, and 36 (17.5%) did not know about cervical cancer screening.
Education with our information sheet was thus associated with an effective impact on the women’s positive intentions (p < .0001) (). We also assessed several factors that were likely to influence their intentions. The multivariate logistic regression model demonstrated that her family members have had cervical cancer screening that was significantly associated with a positive intention to having cervical cancer screening herself. ().
Table 4. Intention to have cervical cancer screening
Table 5. Multivariate with Cox proportional hazards regression analysis on intention to have cervical cancer screening
Attitude about HPV vaccination
We asked the 343 unvaccinated women in our total survey group what they thought as to whether or not they wished they had been vaccinated. Among the sheet-educated women, 46 (26.9%) answered that they wished they had been vaccinated, 17 (9.9%) answered they didn’t think so, and 108 (63.2%) did not answer the question. Among the non-educated women, 31 (18.0%) answered that they wished they had been vaccinated, 17 (9.9%) answered that they didn’t think so, and 124 (72.1%) did not answer the question. The educated women tended to have a more positive attitude about HPV vaccination than the non-educated women (p = .134), but the difference is not significant (). Among the non-vaccinated women, we assessed several factors that were likely to influence their attitudes toward screening and vaccination. The multivariate logistic regression model demonstrated that having talks with family members about cervical cancer was significantly associated with a positive attitude about HPV vaccination ().
Table 6. Attitude toward HPV vaccination
Table 7. Multivariate analysis of attitude about HPV vaccination
Discussion
For women who grew up during the period of the HPV-recommendation-suspension, we could improve their intention toward having cervical cancer screening by an educational intervention. Especially for the vastly larger group of unvaccinated women, the intention to having cervical cancer screening was increased significantly in the sheet-educated group. We think the reason for this improvement was that there were comments on the sheet that unvaccinated women are defenseless against HPV and that cervical cancer screening was their only means for the prevention of cervical cancer. Among the reasons for having a positive intention toward having cervical cancer screening, we assessed what factors influenced their positive intention the most. Our study revealed that having cervical cancer screening among her family members was significantly associated with the woman’s positive intention to having cervical cancer screening herself. This suggested that the health consciousness of a woman’s family influenced their health consciousness.
The intention toward cervical cancer screening between the educated group and the non-educated group was not different and high, 71% and 73% in vaccinated women. We assumed the reason was that they might have received some information about cervical cancer screening when they vaccinated. Hence, the intention toward cervical cancer screening of non-educated women was also high degree.
We previously reported the rate comparison of having cervical cancer screening between vaccinated women and unvaccinated women when the Japanese government’s positive recommendation for HPV vaccination was still in effect. Their vaccination rate was 64.2%. The cervical screening rate in vaccinated women was 6.4% and 3.9% in the unvaccinated,Citation12 which is the opposite of what is needed. Of course, cervical cancer screening is necessary for all women, but we think that it tends to be much more critical for unvaccinated women. It is necessary for our medical professionals to strongly recommend cervical cancer screening for all unvaccinated women starting at age 20.
Our study revealed that unvaccinated women in the sheet-educated group tended to have a more positive attitude regarding that they wished they had been vaccinated, and having a family history of cervical cancer screening and talks with family about cervical cancer had a positive effect on their level of knowledge about the disease and their state of health consciousness. Hence, they tended to receive our educational messages more easily. However, their level of knowledge was assumed to be insufficient to assure they’re seeking the protective HPV vaccine in the current environment of widespread public suspicion of the vaccine due to the past highly publicized reports of alleged adverse medical events.
We previously reported that when their government’s recommendation for HPV vaccination was still in effect (the vaccination-recommended group) women understood more about the HPV vaccine and the best timing for HPV vaccination than women coming of age during the last seven years, while the government suspension has been in effect (the recommendation-suspended group). We found that women in the vaccination-recommended group had more chances to talk with their families about cervical cancer, and they were more afraid of acquiring the disease. The cervical cancer screening rate of the vaccination-recommended group was also significantly higher than for the recommendation-suspended group.Citation13 From our current study, we find that talking about cervical cancer with their family is very important for promoting HPV vaccination and cervical cancer screening as these women come of age.
We conclude from our studies that strong educational intervention will play an important role in promoting HPV vaccination and cervical cancer screening. In a previous study, we found that, under the hypothetical scenario of a restart of the government’s recommendation for the vaccine, the rate of mothers who would be thereafter willing to encourage their daughters to get the HPV vaccine increased significantly, from 12.1% to 21.0% following reading an education leaflet we provided. Educating mothers about the HPV vaccine and HPV-caused cancers positively changed their attitude toward the HPV vaccine and raised the rate of likely encouragement to 27.3%.Citation14 We also found that an educational intervention can promote a father’s positive attitude to HPV vaccination, which could be an additional effective means to improve the vaccination rates of their daughters.Citation15
We report here, for the first time, on the direct interview and intervention with women who had experienced the suspension of MHLW official recommendation for HPV vaccination and are coming of age for cervical cancer screening. Our previous interviews and interventions were targeted at their mothers and fathers. This study is a landmark report because it reveals for the first time how this cohort of women think about whether or not they wished they had been vaccinated. About their attitude about HPV vaccination, 26.9% of the sheet-educated women and 18.0% in even non-educated women answered that they wished they had been vaccinated. On the other hand, only 9.9% answered that they didn’t think so in both educated and non-educated women, and 63.2% of the educated women and 72.1% of the non-educated women did not answer the question. The reasons as to why they did not answer this specific question are unclear at this time but may indicate they are unsure of their reasons for not seeking the vaccine. The difference of the unanswered women between educated women and non-educated women, 8.9%, was the same rate of the difference of women who had a positive attitude about HPV vaccination. An educational intervention could move 8.9% of the women from the unanswered group into the positive attitude group. We have now found that educational intervention can promote a more positive attitude toward HPV vaccination and cervical cancer screening, and not only for the parents but also the women themselves.
Our study has two limitations. First, in this investigation, the sheet included information regarding the morbidity of cervical cancer, the necessity of cervical cancer screening, and their defenselessness for HPV. Detailed information about the alleged adverse medical events following HPV immunization, and the debunking of those allegations, was not included. Our educational intervention sheet excluded information about the allegations of adverse effects, and this may have been responsible for leading these women more toward a positive attitude about HPV vaccination than previous efforts by the government that included that information. Second, the participants were selected from the internet survey panel, which might not reflect the real world. Sixty percent of the non-educated group also answered they have positive intention toward cervical cancer screening, which is different from the low rate of cervical cancer screening in Japan. This discrepancy between the rate of positive intention in the survey and the rate of receiving cervical cancer screening in the real world was also observed in our previous reports.Citation16,Citation17 We think that it is necessary to improve the rate of positive intention in internet survey at the very beginning in order to address the difficult problem to improve the rate of receiving cervical cancer screening in the real world.
Conclusions
For women who came of age during the suspension of the MHLW’s official recommendation for HPV vaccination, we have shown that an educational intervention significantly promotes the women’s intention toward having cervical cancer screening as something they need. Educational intervention and talking about cervical cancer with their families are two very important means of promoting HPV vaccination and cervical cancer screening.
Disclosure of potential conflicts of interest
No potential conflicts of interest were disclosed.
Acknowledgments
We would like to thank Dr. G.S. Buzard for his constructive critique and editing of our manuscript.
References
- Ueda Y, Enomoto T, Sekine M, Egawa-Takata T, Morimoto A, Kimura T. Japan’s failure to vaccinate girls against human papillomavirus. Am J Obstet Gynecol. 2015;212(3):405–06. doi:10.1016/j.ajog.2014.11.037.
- Yagi A, Ueda Y, Egawa-Takata T, Tanaka Y, Nakae R, Morimoto A, Terai Y, Ohmichi M, Ichimura T, Sumi T, et al. Realistic fear of cervical cancer risk in Japan depending on birth year. Hum Vaccin Immunother. 2017;13(7):1700–04. doi:10.1080/21645515.2017.1292190.
- Ikeda S, Ueda Y, Yagi A, Matsuzaki S, Kobayashi E, Kimura T, Miyagi E, Sekine M, Enomoto T, Kudoh K. HPV vaccination in Japan: what is happening in Japan? Expert Rev Vaccines. 2019;18(4):323–25. doi:10.1080/14760584.2019.1584040.
- Hanley SJ, Yoshioka E, Ito Y, Kishi R. HPV vaccination crisis in Japan. Lancet. 2015;385(9987):2571. doi:10.1016/S0140-6736(15)61152-7.
- Ueda Y, Yagi A, Nakayama T, Hirai K, Ikeda S, Sekine M, Miyagi E, Enomoto T. Dynamic changes in Japan’s prevalence of abnormal findings in cervical cytology depending on birth year. Sci Rep. 2018;8(1):5612. doi:10.1038/s41598-018-23947-6.
- Yagi A, Ueda Y, Ikeda S, Sekine M, Nakayama T, Miyagi E, Enomoto T. Evaluation of future cervical cancer risk in Japan, based on birth year. Vaccine. 2019;37(22):2889–91. doi:10.1016/j.vaccine.2019.04.044.
- Masayuki S, Risa K, Manako Y, Sharon JBH, Megumi H, Sosuke A, Yutaka U, Etsuko M, Sayaka I, Asami Y, et al. Japan’s ongoing crisis on HPV vaccination. Vaccines. 2020;8(3):362. doi:10.3390/vaccines8030362.
- Luostarinen T, Apter D, Dillner J, Eriksson T, Harjula K, Natunen K, Paavonen J, Pukkala E, Lehtinen M. Vaccination protects against invasive HPV-associated cancers. Int J Cancer. 2018;142(10):2186–87. doi:10.1002/ijc.31231.
- Lei J, Ploner A, Elfström KM, Wang J, Roth A, Fang F, Sundström K, Dillner J, Hpv SP. Vaccination and the risk of invasive cervical cancer. N Engl J Med. 2020;383(14):1340–48. doi:10.1056/NEJMoa1917338.
- Yagi A, Ueda Y, Nakagawa S, Ikeda S, Tanaka Y, Sekine M, Miyagi E, Enomoto T, Kimura T. Potential for cervical cancer incidence and death resulting from Japan’s current policy of prolonged suspension of its governmental recommendation of the HPV vaccine. Sci Rep. 2020;10(1):15945. doi:10.1038/s41598-020-73106-z.
- Ueda Y, Yagi A, Ikeda S, Enomoto T, Kimura T. Beyond resumption of the Japanese Government’s recommendation of the HPV vaccine. Lancet Oncol. 2018;19(12):1563–64. doi:10.1016/S1470-2045(18)30573-4.
- Taniguchi M, Ueda Y, Yagi A, Ikeda S, Endo M, Tomimatsu T, Nakayama T, Sekine M, Enomoto T, Kimura T. Cervical cancer screening rate differs by HPV vaccination status: an interim analysis. Vaccine. 2019;37(32):4424–26. doi:10.1016/j.vaccine.2019.06.064.
- Miyoshi A, Ueda Y, Yagi A, Taniguchi M, Sekine M, Enomoto T, Kimura T. Health consciousness and cervical cancer screening rates in HPV-unvaccinated girls: comparison from HPV-recommended and HPV-recommendation-suspended program periods. Hum Vaccin Immunother. 2020;3:1–5.
- Yagi A, Ueda Y, Egawa-Takata T, Tanaka Y, Morimoto A, Terai Y, Ohmichi MCT, Sumi T, Murata H, Okada H, et al. Development of an efficient strategy to improve HPV immunization coverage in Japan. BMC Public Health. 2016;16(1):1013. doi:10.1186/s12889-016-3676-7.
- Miyoshi A, Takiuchi T, Kimura T. HPV vaccination in Japan: can educational intervention promote a father’s intention to encourage his daughter’s vaccination? Int J Clin Oncol. 2020;25(4):746–54. doi:10.1007/s10147-019-01575-y.
- Taniguchi M, Ueda Y, Yagi A, Miyoshi A, Tanaka Y, Minekawa R, Endo M, Tomimatsu T, Hirai K, Nakayama T, et al. Disparity of cervical cancer risk in young Japanese women: bipolarized status of HPV vaccination and cancer screening. Vaccines (Basel). 2021;9(3):280. doi:10.3390/vaccines9030280.
- Egawa-Takata T, Ueda Y, Morimoto A, Tanaka Y, Yagi A, Terai Y, Ohmichi M, Ichimura T, Sumi T, Murata H, et al. Motivating mothers to recommend their 20-year-old daughters receive cervical cancer screening: a randomized study. J Epidemiol. 2018;28(3):156–60. doi:10.2188/jea.JE20160155.