What information can change the attitude of teachers toward the human papillomavirus vaccine?

Transcription

1 doi: /jog J. Obstet. Gynaecol. Res. Vol. 44, No. 4: , 2018 What information can change the attitude of teachers toward the human papillomavirus vaccine? Masaharu Kamada 1, Hiroaki Inui 1, Tomohiro Kagawa 1, Ayuka Mineda 1, Takao Tamura 1, Tomohito Fujioka 2, Takahiro Motoki 2, Hiroki Hirai 2, Eiichi Ishii 3 and Minoru Irahara 4 1 Department of Obstetrics and Gynecology, and 2 Department of Pediatrics, Shikoku Central Hospital of the Mutual Aid Association of Public School Teachers, Shikoku-chuo, 3 Department of Pediatrics, Ehime University Graduate School of Medicine, Toon and 4 Department of Obstetrics and Gynecology, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan Abstract Aim: We conducted a self-administered survey on the perception of teachers toward human papillomavirus (HPV) vaccine to determine the ways to increase their willingness to encourage its use. Methods: Answers were obtained both prior to and after having the teachers read five brief information articles: (i) cervical cancer knowledge, (ii) vaccine knowledge, (iii) result of a survey in Nagoya, (iv) news report of the World Health Organization statement and (v) articles written by Dr Muranaka, a journalist. Results: Most of the respondents (180/247) did not know about the natural history of cervical cancer. Only 36% knew that HPV is the cause of cervical cancer, although 63% knew that HPV vaccine would prevent cervical cancer. Few respondents had knowledge regarding adverse events following immunization and the survey results from Nagoya. Among those who were initially negative for the HPV vaccine, only 43% revealed that they fully understood its safety and only 29% reversed their opinion to recommend vaccination to their daughters and/or students, even after reading our informational material. The most useful information for changing their attitudes was to increase their understanding of vaccines and informing them about Nagoya city survey results. They mostly wanted a proof of the preventive effects of the vaccine on cervical cancer in Japan. Conclusion: Gynecologists and pediatricians must proactively communicate accurate scientific information to the government and the media to spread awareness among people in Japan. Also, we must try to demonstrate the capabilities of this vaccine to prevent cervical cancer and/or its precancerous lesions. Key words: adverse event following immunization, adverse reaction, attitude survey, human papillomavirus vaccine, uterine cervical cancer. Introduction Uterine cervical cancer develops from an intraepithelial neoplasm (dysplasia), precancerous lesion of the cervix caused by chronic infection from the human papillomavirus (HPV). 1 Therefore, an HPV vaccine could prevent the development of cervical cancer by blocking the development of HPV infection in the uterine cervical epithelial cells. 2 Cervical cancer is one of the most important diseases affecting women. It is the fourth most common cancer in terms of its incidence and morbidity worldwide. 3 In Japan, the mortality rate from cervical cancer has increased substantially, particularly among women aged years. 4 Notably, this disease takes away the lives of many young women who are involved in childcare or are giving birth, and even for the survivors, most therapeutic alternatives lead to Received: August Accepted: December Correspondence: Masaharu Kamada, Department of Obstetrics and Gynecology, Shikoku Central Hospital of the Mutual Aid Association of Public School Teachers, 2233 Kawanoe, Shikoku-chuo, Ehime, , Japan. kamada-m@shikoku-ctr-hsp.jp Japan Society of Obstetrics and Gynecology

2 Attitude of teachers toward HPV vaccine the loss or impairment of their reproductive function. In 2009, the World Health Organization (WHO) recommended that HPV vaccination be introduced into national immunization programs, as there were many evidences of its safety and effectiveness. 3 However, in Japan, a policy of proactively recommending the use of HPV vaccination through a national program was suspended only 2 months after it was introduced in April 2013, because of complaints of adverse vaccine reactions. 5 Sensational reports of only a few girls suffering from convulsions or numbness, supposedly as side effects of the HPV vaccine, were repeatedly broadcasted on TV and many people developed a substantial fear of potential adverse reactions. In January 2014, the council of the Ministry of Health, Labor and Welfare (MHLW) on cervical cancer vaccines concluded that the reported symptoms, such as chronic pain, were psychosomatic reactions due to the pain of the injection itself or due to anxiety regarding vaccination. 6 In addition, many academic societies in Japan such as The Japan Society of Obstetrics and Gynecology and The Japan Pediatric Society repeatedly urged the government to resume its proactive recommendations encouraging immunization for HPV. 4,7 Furthermore, the WHO warned the Japanese government about making major health policy decisions based on weak evidence. 8 However, since a majority of the media did not report these messages, many people continued to fear the alleged side effects and to believe that pharmacological injury could be caused by the HPV vaccine. In this study, we conducted a self-administered questionnaire survey on the attitude toward HPV vaccine held by public school teachers, who of course have a substantial influence on children and also on their parents. 9 We had the respondents first answer the questions prior to their receiving any new information about this general topic. We then had them read five different informational documents that explain the science and evidence regarding the effectiveness of the HPV vaccine. Our goal was to see what type of new information could be the most effective in helping adjust their viewpoints toward objectively scientific evidence regarding this vaccine. Methods Subjects and methods The protocol of this study was approved by the Institutional Review Board of the Shikoku Central Hospital for the Mutual Association of Public School Teachers. This questionnaire was administered in February 2016 and analyzed anonymously. We mailed a letter explaining the purpose and method of the survey, along with the questionnaire, informational documents and a return envelope to 846 public school teachers in Shikoku district, who were randomly selected from our database among medical examination receivers in the hospital during 2015 fiscal year. A total of 100 women and men each in their 30s, 123 in their 40s, 100 in their 50s and 100 in their 60s were included. We regarded anyone who answered and sent back the questionnaire as a participant who indicated his/her informed consent regarding this survey. Follow-up of respondents and reminder contact with nonrespondents were not conducted. In the documents sent out, the following five informational pieces, which were considered useful for acceptance of HPV vaccine by the teachers, were provided. The first was an article describing cervical cancer and HPV. 10 It specially explained that persistent infection by the HPV virus can cause the development of neoplasms of the uterine cervical epithelium followed by cancer in some cases, and that the occurrence of cervical cancer can be prevented by screening and use of the HPV vaccine. Furthermore, it clarified that chronic regional pain syndrome (CRPS), often alleged in Japan as a side reaction after HPV vaccination, is not a special disorder. The CRPS is induced by any kind of injections or injuries, and there are remarkably no reports of CRPS related to HPV vaccine in any countries except Japan. The second informational item was an article describing the nature and effectiveness of vaccines. We have prepared the article with reference to Dr Konno s paper for this survey. 11 That is, in all human history, one of the greatest medical contributions has been vaccination, which has saved innumerable millions of lives and prevented the tragic sequels from many lethal or terrible diseases such as small pox, Japanese encephalitis, poliomyelitis, measles and so on. This article also explained that, in Japan, virtually all adverse events following immunizations (AEFI) were reported as adverse reactions (side effects) to the vaccine being administered, 12 despite the evidence that the vast majority of the events thought to be related to the administration of a vaccine were actually not due to the vaccine itself but were simply coincidental. 13 In order to determine whether a reported AEFI is an adverse reaction to a vaccine or merely a 2018 Japan Society of Obstetrics and Gynecology 779

3 M. Kamada et al. coincidental event, it is necessary to compare the observation rate of the AEFI to the background rate in an unvaccinated population. Except for mild reactions known as common side effects to vaccines such as a sore arm from the shot, fever and so on, none of the serious adverse reactions to the HPV vaccine, where the observation rate is higher than the background rate, have been reported. 14 This article also pointed out that previously there have been tragic cases of pertussis and rubella returning of epidemic numbers after the suspension of vaccine programs in Japan aimed at preventing these particular diseases. The third informational item sent to the teachers was a report about a survey done in Nagoya, a large city in the center of Japan, on the occurrence of adverse events following HPV vaccinations. 15 This survey addressed 24 symptoms being claimed as adverse vaccine reactions, and it was filled out by approximately female residents, almost all young girls equivalent to the generations of students between the third grade of junior high school and the third grade of the university in Nagoya. There were no symptoms that significantly increased in the subjects who had received the HPV vaccination compared to the unvaccinated age-matched girls. The fourth informational item was a newspaper article on the statement of the WHO advisory committee on vaccine safety. Namely, in December 2015, the WHO issued a statement on the safety of the HPV vaccine and recommended its introduction into national immunization programs. It also specifically warned Japan that policy decisions based on weak evidence, leading the lack of use of safe and effective vaccines, can result in real harm. 8 The fifth informational item in the package introduced the teachers to a web site, which features articles written by Dr Riko Muranaka, who is both a medical doctor and a journalist. 16 She has criticized the mass media that sensationally reported only the lopsided claims of various antivaccine groups, often supported by physicians who mislead people by using unscientific criticism against the HPV vaccine. She also clarified that, as a therapy, in some of these adverse cases mentioned by antivaccine groups, additional drugs, which are used to treat autoimmune diseases or dementia, were also being administered to the young girls whom they insisted were a victim of the HPV vaccine, and that in some of these adverse cases unrelated and extremely invasive methods, such as spinal cord electrical stimulation, were being utilized. Questionnaire The survey included 16 questions about uterine cervical cancer and the HPV vaccine. We asked if they already knew about each of the 11 fundamental concepts involved with this topic, whether they thought that the vaccine was safe, and if they would like to recommend HPV vaccine to their daughters and/or students. For 13 of these questions, if they answered I did not know or No, we further asked if their uncertainties were clarified after reading our five informational documents. In addition, to those who initially thought that the side effects were scary and/or initially did not intend to recommend vaccination but were able to change their attitude after reading our material, we asked which of the five items had been the most useful in changing their minds. Finally, to those who were still scared of the vaccine and/or did not want to recommend even after studying our material, we asked what kind of further information could change their mind and encourage them to recommend the vaccination. Statistical analysis Analysis was performed by the chi-squared test. Values of P < 0.05 were considered to be significant. The XLSTAT-Pro 2014 (Addinsoft, NY) was used for statistical analysis. A few teachers who had no answer (n = 1 4) were excluded from each analysis. Results Participants Of the 846 teachers who received the survey, 247 (29.2%) answered our questionnaire. The numbers of respondents were as follows: 45 in their 30s, 65 in their 40s, 54 in their 50s, 81 in their 60s and 145 females and 92 males. Two were unclassified in age and 10 in gender. Response rate in women seems to be higher than that in men, because there was statistical significance (P < 0.05) even if all 10 unclassified respondents were male. Questionnaire and answer Table 1 shows how many respondents already knew about each of the 11 important medical issues relevant to this topic, receiving our information. To the respondents who did not know, we further asked if they understood these key issues after reading our five educational items Japan Society of Obstetrics and Gynecology

4 Attitude of teachers toward HPV vaccine reading our material As shown in Table 1 (Items 1 11), about 62% of our respondents knew that cervical cancer is increasingly common in young women (Item 1) and a remarkable 87% knew that approximately 3500 people die each year from it (Item 2). However, about three quarters of the teachers (73%) who responded did not know about dysplasia and the natural history of cervical cancer (Item 3). Regarding HPV itself, only 36% of respondents knew that it is the cause of cervical cancer (Item 4), but 63% were aware that the HPV vaccine would prevent this particular disease (Item 5). Female teachers had significantly better knowledge regarding the Items 3 5 compared to male teachers (32% vs 17% in Item 3, P < 0.02; 46% vs 24% in Item 4, P < 0.001; 71% vs 52% in Item 5, P < 0.005). For Items 1 and 4, the young teachers (30s + 40s) had significantly better knowledge compared to the elder teachers (50s + 60s) (69% vs 56% in Item 1, P < 0.05; 46% vs 30% in Item 4, P < 0.02). On the other hand, relatively few respondents (3 13%) had knowledge of AEFI and of adverse reactions to vaccines generally (Items 6 9). In particular, only 6% knew about the survey results from Nagoya, where it clearly revealed that there were no adverse events suspected of being related to the HPV vaccine (Item 10). In addition, only 19% of our respondents knew that the WHO had issued a statement on the safety of HPV vaccine and had recommended its introduction into national immunization program (Item 11). Finally, a remarkable 77% of the respondents expressed fear about the possible side effects of the HPV vaccine and 69% indicated that they did not recommend the vaccine to their daughters or students (Items 12 and 13 in Table 1). Effect of our educational material reading the brief reports included with the package received by all respondents, most (72 91%) replied that they now better understood the 11 key medical issues on this topic, which they had formally not appreciated (Items 1 11 in Table 1). However, of those who initially answered that they regarded the side effects of the HPV vaccine to be frightening, only 43% subsequently changed their minds about its safety after reading our five educational materials (Item 12 in Table 1). More specifically, 23% answered that it was still scary and 32% indicated that they remained uncertain, even after reading the five articles we provided. Also remarkable was the result that of those who initially answered that they did not intend to recommend vaccination to their daughters and/or students, only 29% changed their minds in favor of recommending vaccination after reading our material (Item 13 in Table 1). This total broke down as 10% saying that they would not recommend the vaccine, and 60% indicated that they remain unsure about this issue, even after reading our five documents. The response rate to these questionnaires was not different between males and females. Compared to the elder teachers, a significantly lower percentage of the young teachers changed their attitudes even after reading our educational materials (Table 2). What kind of information is useful to change the attitude? Items 14 and 15 (Table 1) show which of the five educational items were the most useful in changing the attitude of those who initially thought that side effects were scary, and of which ones were most effective for respondents who initially did not intend to recommend vaccination. In these questions, multiple answers were allowed. For both of these groups, the most useful educational item turned out to be the article describing the vaccine itself and the second was the result of the Nagoya survey. Finally, we asked what kind of information could cause those who answered No in Questions 12 and 13 to now actually recommend vaccination, and again multiple answers were allowed. It was clear that the information they most wanted to obtain was a proof of the preventive effect on cervical cancer provided by the HPV vaccine in Japan (Item 16 in the Table 1). For this question, there were no statistical differences between males and females, and between the young and the elder. Discussion The majority of teachers in our study already knew that cervical cancer is increasing in young women, that many women die from this cancer every year, and that the HPV vaccine can prevent this particular type of cancer. For these fundamental issues, female and the young teachers had better knowledge compared to male and the elder teachers, respectively. It seems that young women have more concern about cervical cancer. However, they were not well aware of the natural history of cervical cancer, that is, it 2018 Japan Society of Obstetrics and Gynecology 781

5 M. Kamada et al. Table 1 Questionnaires and answers from respondents 1. Cases with cervical cancer are increasing in young women in their 20s and 30s. I already knew 152 (62%) I understood 81 (81%) I did not know 94 (38%) I am not sure 7 (8%) No answer 1 (0%) No answer 6 (6%) 2. Approximately 3500 people died annually. I already knew 29 (12%) I understood 189 (87%) I did not know 216 (87%) I am not sure 4 (2%) No answer 2 (1%) No answer 23 (11%) 3. The precancerous lesion (dysplasia) of cervical cancer lasts few years to decades and development to cancer can be prevented by easy surgery for the dysplasia. I already knew 65 (26%) I understood 163 (91%) I did not know 180 (73%) I am not sure 2 (1%) No answer 2 (1%) No answer 15 (8%) 4. Most of cervical cancer is caused by HPV infection. I already knew 90 (36%) I understood 134 (88%) I did not know 153 (62%) I am not sure 5 (3%) No answer 4 (2%) No answer 14 (9%) 5. The HPV vaccine can prevent the onset of cervical cancer. I already knew 157 (63%) I understood 76 (86%) I did not know 88 (36%) I am not sure 5 (3%) No answer 2 (1%) No answer 7 (8%) 6. AEFI can be divided into coincidental adverse events and adverse reactions (side effects), which may be related to the vaccination. I already knew 32 (13%) I understood 175 (83%) I did not know 212 (86%) I am not sure 21 (10%) No answer 3 (1%) No answer 16 (7%) 7. In Japan, all AEFI were reported as adverse reactions to vaccine. I already knew 15 (6%) I understood 186 (81%) I did not know 230 (93%) I am not sure 27 (12%) No answer 2 (1%) No answer 17 (7%) 8. Even for events suspected as adverse reactions, there are true adverse reactions caused by vaccination and still coincidental events. I already knew 15 (6%) I understood 186 (81%) I did not know 230 (93%) I am not sure 27 (12%) No answer 2 (1%) No answer 17 (7%) 9. When comparing between the rates of adverse event in the immunization group and in the nonimmunization group of the similar population, an event that shows higher rate in the former is considered adverse reaction to vaccine. On the other hand, if the rates of the events in both groups are not different, it should be considered coincidental event. I already knew 8 (3%) I understood 170 (72%) I did not know 236 (96%) I am not sure 51 (22%) No answer 3 (1%) No answer 15 (6%) 10. In the survey taken in Nagoya, there were no symptoms that significantly increased in the subjects with HPV vaccination compared to the unvaccinated age-matched girls. I already knew 16 (6%) I understood 181 (79%) I did not know 229 (93%) I am not sure 32 (14%) No answer 2 (1%) No answer 16 (7%) (Continues) Japan Society of Obstetrics and Gynecology

6 Attitude of teachers toward HPV vaccine Table 1 Continued 11. Due to analyzing reports of suspected adverse reactions and comparative surveys with background incidence rates in various countries including Japan, WHO has issued a statement on the safety of HPV vaccine and recommended its introduction into national immunization program. I already knew 46 (19%) I understood 161 (81%) I did not know 199 (80%) I am not sure 23 (12%) No answer 2 (1%) No answer 15 (7%) 12. Do you think HPV vaccine is safe? Yes 53 (22%) Yes 83 (43%) No 191 (77%) I am not sure 62 (32%) No answer 3 (1%) No 43 (23%) No answer 15 (7%) 13. Do you recommend HPV vaccine to your daughters and/or students? Yes 73 (29%) Yes 49 (29%) No 170 (69%) I am not sure 103 (60%) No answer 4 (2%) No 17 (10%) No answer 1 (1%) 14. To those who initially thought that side reactions were scary but changed their attitude after reading the informational material in Question 12 (n = 83). Which items had been the most useful? (Multiple answers are allowed.) Knowledge of cervical cancer 33.7% Vaccine knowledge 83.1% Result of survey in Nagoya City 57.8% News report of WHO statement 43.4% Articles written by Ms Muranaka 22.9% 15. To those who initially did not intend to recommend vaccination but who changed their attitude after reading the information we provided in Question 13 (n = 49), which educational materials had been the most useful? (Multiple answers are allowed.) Knowledge of cervical cancer 40.8% Vaccine knowledge 83.7% Result of survey in Nagoya City 53.1% News report of WHO statement 44.9% Articles written by Ms Muranaka 20.4% 16. What kind of information could change the attitude so that those who answered No in Questions 12 (n = 43) and 13 (n = 17) could recommend vaccination? (Multiple answers are allowed.) To resume proactive recommendation by the government (n = 10). The nationwide survey on safety of the HPV vaccine (n = 12). Proof of the preventive effect of cervical cancer by the HPV vaccine in Japan (n = 20). Statement of WHO and/or other international organization (n = 12). News reporting safety of the HPV vaccine by mass media (n = 11). Others (n = 8). Development of new HPV vaccine (n = 2). Thorough implementation of municipal compensation system (n = 1). Whatever information I get, vaccine is not recommended (n = 4). No comment (n = 1). AEFI, adverse events following immunization;, answer after reading information; HPV, human papillomavirus vaccine; Ms Muranaka, is both a medical doctor and a journalist;, answer prior to reading information; WHO, World Health Organization. develops from an intraepithelial neoplasm (dysplasia), which is a precancerous lesion caused by persistent infection from HPV. The antivaccine group insists that the preventive effect on cervical cancer itself by the HPV vaccine has not been established, although the preventive effect of the vaccine on precancerous lesions has clearly been verified. 17 Considering the natural history of cervical cancer, their assertion is obviously a mistake. Preventing the occurrence of precancerous lesions (dysplasia) is the key to preventing the development of cervical cancer. Gynecologists must prepare and disseminate accurate knowledge about cervical cancer, such as its proximate causes. The WHO explains that AEFI is any untoward medical occurrence that follows immunization, but 2018 Japan Society of Obstetrics and Gynecology 783

7 M. Kamada et al. Table 2 Attitude after reading educational materials 12. Do you think HPV vaccine is safe? Young (30s + 40s)* Elder (50s + 60s)* Yes 33 (38%) Yes 49 (49%) I am not sure 26 (30%) I am not sure 36 (36%) No 28 (32%) No 15 (15%) 13. Do you recommend HPV vaccine to your daughters and/or students? Young (30s + 40s)** Elder (50s + 60s)** Yes 13 (17%) Yes 36 (40%) I am not sure 55 (71%) I am not sure 48 (53%) No 10 (13%) No 7 (8%) *P < 0.05; **P < and Values are shown as n (%). Teachers who had no answer were excluded in these analyses (4 in Item 12; 1 in Item 13). HPV, human papillomavirus. does not necessarily have a causal relationship with the actual vaccine being used, and that the majority of events thought to be related to the administration of a vaccine are actually not due to the vaccine itself, but are simply coincidental events. 13 The terms adverse event and adverse reaction need to be clearly distinguished. Carefully designed surveillance programs are necessary to detect rare vaccine adverse events, and accordingly various vaccine adverse events reporting system have been established in many countries, including Japan. However, in Japan s reporting system, the term adverse reactions to vaccine has been used, even when the term AEFI or suspected adverse reactions to vaccine should have been used. Namely, all cases that should have been discussed as AEFI or suspected adverse reactions to vaccine were instead incorrectly described as adverse reactions to vaccine in the document published by the MHLW and this terminology was in turn used by the mass media. As a result substantial unwarranted anxiety and misunderstanding were experienced throughout the general public. 18 In August 2016, the MHLW revised the Act to eliminate use of the term adverse reaction to vaccine and replace it with words: suspected adverse reaction to vaccine. 12 The surveillance system in the United States has the capability to analyze reported adverse events to detect possible associations between the vaccine involved and numerous prespecified diseases by using a variety of sophisticated databases. 19 When comparing the rates of adverse events in the immunization group and in the nonimmunization group of a similar population, an event that shows a higher rate in the former is considered to be an adverse reaction to a vaccine. On the other hand, if the rates of the events in both groups are not different, it is of cause considered a coincidental event. Using such reporting systems and their relevant databases, it is possible to analyze with the reported adverse events rapidly and effectively. No statistically significant increased risks for any of the prespecified adverse events after HPV vaccination has been detected. 20,21 The European Medical Agency concluded that the evidence does not support a causal link between the vaccines and development of either CRPS or postural orthostatic tachycardia syndrome (POTS), which, in Japan, are considered by some individuals as being sympathetically mediated disorders induced by the HPV vaccine, because their rates after HPV vaccination were consistent with what would be expected in the corresponding age groups. 22 Such thorough and immediate scientific responses to alleged adverse reactions from immunization are important for governments in many countries to continue executing, so that critical public health efforts such as the HPV vaccination program continue to be confidently carried out, and also to ensure that actual vaccine-associated adverse events are promptly identified and appropriately addressed. In our survey, it turned out that few teachers had good understanding about vaccines, or about the difference between an AEFI and an actual verified adverse reaction to a vaccine. They also had little information regarding the survey in Nagoya, which clearly showed the safety of the HPV vaccine. Without this information, it was inevitable that many teachers were fearful of possible side effects from the HPV vaccine, and that they would therefore not recommend it to their daughters and/or students. It seems that the most useful information to change the attitude of those who initially did not intend to recommend vaccination was the article describing the power of vaccine in general and the HPV one in particular, and that the second most persuasive was the result of the Nagoya survey. These results seem to be Japan Society of Obstetrics and Gynecology

8 Attitude of teachers toward HPV vaccine in agreement with the previous reports. Tung et al. reported that the main reason reported for HPV nonvaccination was parental concern about vaccine safety. 23 Brown et al. suggested that common factors influencing parents, as well as adolescents, intent to vaccinate are the first strength of physician recommendation, followed by the availability of information regarding the importance of the vaccine. 24 However, even after reading our information, only 43% of the teachers answered that they understood the safety of the HPV vaccine, and only 29% indicated that they would recommend it to their daughters and/or students. A poor acceptance of the HPV vaccine even after providing educational materials was recognized especially in the young teachers. The age of this group seems to be equivalent to that of the parents with children who are recommended vaccination. Unfortunately, these results also seem to represent the broad sentiments of the general public in Japan. This appears to be due to the incomplete measure taken by the MHLW such as its suspension of actively recommending HPV vaccination, on the reasoning, in Japan, the surveillance system to detect associations between the vaccines and prespecified diseases is still not adequately developed. In particular, the correct term suspected adverse reaction to vaccine was replaced by the phrase adverse reaction to vaccine, and there are at present remarkably no database systems that can appropriately relate records of vaccinations against numerous diseases to appropriately selected prespecified adverse events. The Pharmaceutical and Medical Device Regulatory Science Society of Japan emphasizes the importance of providing timely and accurate scientific information. 18 Specifically, to prevent the spread misinformation, it recommends that the government should quickly issue clear information regarding the safety of vaccines, the validity of which is sufficiently guaranteed. They also point out that it is important for the media, which plays an important role in communicating this type of information, to all areas of the public, to fully understand the scientific content of this information and present it in a way that is widely understandable. As an important step in improving the public knowledge about vaccines, in August 2016, the MHLW revised the Act to use the correct term suspected adverse reactions to vaccine. As a next step, we hope to establish registration systems on diseases and on vaccinations, which will include careful health surveys following immunization programs. Finally, to those who still thought that side effects were scary and to those who did not intend to recommend vaccination even after reading our educational material, we asked what kind of information could change their attitudes in favor of vaccination. It turned out that the data they would most like to have was clear proof of the preventive effect of cervical cancer provided by the HPV vaccine in Japan. That is, it is suggested that the most effective strategy convincing the teacher of HPV vaccine is to prove its benefit. Surprisingly, for Japan itself there is no formal scientific study showing that the HPV vaccine prevents the occurrence of precancerous cervical lesions and thereby prevents cervical cancer, though Ozawa et al. reported a significant decrease of the rate of abnormal cervical cytology (2.41%, 8/332) in Japanese women with HPV vaccination compared to the rate in women without HPV vaccination (5.03%, 148/2940, P = 0.03). 25 There are of course numerous studies demonstrating a significant decline of high-grade cervical lesions (cervical intraepithelial neoplasia 2/3) after the implementation of HPV vaccination programs in many countries We must try to demonstrate, and publicize, the preventive effect on cervical cancer and its precancerous lesions through use of the HPV vaccine in Japan. Many serious infectious diseases such as measles and poliomyelitis have been dramatically decreased by the development and widespread use of vaccines. As a result, people today do not fear these diseases, even though concerns about the side effects of vaccines in general are increasing. Under these circumstances, it is important to avoid the spread of unscientific information or rumors throughout the public. We, gynecologists and pediatricians, must continue to communicate scientifically accurate information to the government, media, healthcare providers and certainly also to teachers to help increase the wide dissemination of genuine scientific results across the entire society. Since the response rate was low, the sample size has become a relatively small, especially in the Items 14, 15 and 16. These questions were the most important to turn out what information can change the attitude of teachers toward the HPV vaccine. We analyzed them as the attitude of the teachers, because there were no statistical differences in the tendency of answers between males and females or the young and the elder. Low-response rate in this study may represent the attitude of teachers of unconcern or negative toward the HPV vaccine Japan Society of Obstetrics and Gynecology 785

9 M. Kamada et al. Acknowledgments The authors would like to thank Professor Okahisa, Department of General Medicine and Community Health Science, Institute of Biomedical Sciences, Tokushima University Graduate School, for helpful advices and Enago ( for the English language review. This study was supported by a Grant-in-Aid for Occupational Research on Healthcare and Medical Treatment from Japan Mutual Aid Association of Public School Teachers. Disclosure None declared. References 1. Bosch FX, Manos MM, Muñoz N et al. Prevalence of human papillomavirus in cervical cancer: A worldwide perspective. International biological study on cervical cancer (IBSCC) Study Group. J Natl Cancer Inst 1995; 87: Schiller JT, Castellsagué X, Villa LL, Hildesheim A. An update of prophylactic human papillomavirus L1 virus-like particle vaccine clinical trial results. Vaccine 2008; 26 (Suppl 10): K53 K The World Health Organization. Guide to Introducing HPV Vaccine into National Immunization Programs. Geneva, Switzerland: the WHO Document Production Services, Iwata S, Okada K, Kawana K. Consensus statement from 17 relevant Japanese academic societies on the promotion of the human papillomavirus vaccine. Vaccine 2017; 35: Recommendation of Ministry of Health, Labor and Welfare [Cited 7 Aug 2017.] Available from URL: The 7 th Vaccination Sub-committee Meeting, Investigative Committee on Adverse Reactions, Health Science Council, Ministry of Health, Labor and Welfare [Cited 7 Aug 2017.] Available from URL: shingi2/ html 7. Statement of Japan Society of Obstetrics and Gynecology [Cited 7 Aug 2017.] Available from URL: The World Health Organization, Global Advisory Committee on Vaccine safety Statement on Safety of HPV Vaccines. (Three screens) [Cited 7 Aug 2017.] Available from URL: GACVS_HPV_statement_17Dec2015.pdf?ua=1 9. Gargano LM, Herbert NL, Painter JE et al. Development, theoretical framework, and evaluation of a parent and teacher-delivered intervention on adolescent vaccination. Health Promot Pract 2014; 15: Kamada M. [Gynecologic cancer-cervical cancer and endometrial cancer]. Fukuri Kagawa 2014: 4 5 (In Japanese.) 11. Konno R, Nishi J, Miyagi E, Nakayama T. [Lack of virological and epidemiological evidences for the hypothesis, human papillomavirus associated with neuropathic syndrome (HANS)]. Jpn Med J 2015; 4783: (In Japanese.) 12. Ministry of Health, Labor and Welfare [Cited 7 Aug 2017.] Available from URL: kenkou/kekkaku-kansenshou20/hukuhannou_houkoku/ 13. The World Health Organization, Adverse events following immunization (AEFI). [Cited 7 Aug 2017.] Available from URL: detection/aefi/en/ 14. The World Health Organization, Global Advisory Committee on Vaccine Safety [Cited 7 Aug 2017.] Available from URL: /reports/june_2017/en/ 15. City of Nagoya. [Cited 7 Aug 2017.] Available from URL: 2.html 16. Muranaka R. The truth of Japan s pharmacologic injury. [Cited 7 Aug 2017.] Available from URL: ismedia.jp/articles/-/5510, 5525, 5530, 5756 and Beppu H, Minaguchi M, Uchide K et al. Lessons learnt in Japan from adverse reactions to the HPV vaccine: A medical ethics perspective. Indian J Med Ethics 2017; 2: Pharmaceutical and Medical Device Regulatory Science Society of Japan. Recommendation on the Reporting System of Adverse Reactions to Vaccines and the Development of Infrastructure related to Vaccine Risk Management in Japan. (Eight screens) [Cited 7 Aug 2017.] Available from URL: ENG.pdf 19. Centers for Disease Control and Prevention, Vaccine Safety Datalink [Cited 7 Aug 2017.] Available from URL: ring/vsd/index.html 20. Centers for Disease Control and Prevention, HPV Vaccine Recommendations [Cited 7 Aug 2017.] Available from URL: commendations.html 21. Gee J, Naleway A, Shui I et al. Monitoring the safety of quadrivalent human papillomavirus vaccine: Findings from the vaccine safety datalink. Vaccine 2011; 26: European Medical Agency, Review concludes evidence does not support that HPV vaccines cause CRPS or POTS. Reports of CRPS and POTS after HPV vaccination are consistent with what would be expected in this age group. London: The Agency; 2015 Nov Report No.: EMA/714950/ Tung IL, Machalek DA, Garland SM. Attitudes, knowledge and factors associated with human papillomavirus (HPV) vaccine uptake in adolescent girls and young women in Victoria, Australia. PLoS One 2016; 11: e Brown B, Gabra MI, Pellman H. Reasons for acceptance or refusal of human papillomavirus vaccine in a California pediatric practice. Papillomavirus Res 2017; 3: pii: S (16) Ozawa N, Ito K, Tase T, Metoki H, Yaegashi N. Beneficial effects of human papillomavirus vaccine for prevention of cervical abnormalities in Miyagi, Japan. Tohoku J Exp Med 2016; 240: Japan Society of Obstetrics and Gynecology

10 Attitude of teachers toward HPV vaccine 26. Brotherton JM, Fridman M, May CL et al. Early effect of the HPV vaccination programme on cervical abnormalities in Victoria, Australia: An ecological study. Lancet 2011; 377: Baldur-Felskov B, Dehlendorff C, Munk C, Kjaer SK. Early impact of human papillomavirus vaccination on cervical neoplasia-nationwide follow-up of young Danish women. J Natl Cancer Inst 2014; 106: djt jnci/djt Niccolai LM, Meek JI, Brackney M et al. Declines in HPVassociated high-grade cervical lesions after introduction of HPV vaccines in Connecticut, US, Clinical Infect Dis 2017; 65: Garland SM, Kjaer SK, Muñoz N et al. Impact and effectiveness of the Quadrivalent human papillomavirus vaccine: A systematic review of 10 years of real-world experience. Clin Infect Dis 2016; 63: Japan Society of Obstetrics and Gynecology 787