In Japan, the vast majority of females between 13 and 24 are now unvaccinated for HPV and thus unprotected from HPV-caused cervical cancer. We analyzed the differences among these unvaccinated females regarding their understanding of the HPV vaccine, its role in cervical cancer prevention, and their need for cervical cancer screening – based on whether they refused vaccination when their government's recommendation for HPV vaccination was still in effect (vaccination-recommended group) – or during the last 7 years, while the government suspension was in effect (recommendation-suspended group). The vaccination-recommended group understood more about the HPV vaccine and the best timing for HPV vaccination than the recommendation-suspended group (p < .0001 and p = .002, respectively). We found that girls in the vaccination-recommended group had more chances to talk with the family about cervical cancer and they were more afraid of acquiring the disease (p < .0001 and p < .0001, respectively). The girls in the recommendation-suspended group tended to feel more inhibited from talking about cervical cancer with friends and acquaintances (p = .0262). The cervical cancer screening rate of the vaccination-recommended group was significantly higher (p = .014).
Japan's governmental recommendation of HPV vaccine has now been suspended for more than 4 years. In and before 2013, the targets of 20-year-old cervical cancer screening were females born in and before 1993, i.e., those who could not have received HPV vaccination because it was not yet publicly introduced. The targets during 2014–2019 are, or will be, those born in 1994–1999, i.e., those who came of age during a period with the highest HPV immunization rate. We analyzed the statistical data for each birth year, for the cumulative HPV vaccination rates achieved as of age 16, and for the corresponding results of cervical cancer screening at age 20. The rate of abnormal findings in cervical cytology increased slightly from 3.68% in 2010 (birth year: 1990) to 4.35% in 2013 (birth year: 1993); however, it dynamically dropped to 2.99% in 2014 (birth year: 1994) and 3.03% in 2015 (birth year: 1995). In total, the rate of abnormal findings in cervical cytology was 3.96% in 2010–2013, but significantly dropped to 3.01% in 2014–2015 (p = 0.014). This is the first description of dynamic changes occurring in the abnormal rate of cervical cancer screening as a result of positive changes in national HPV vaccination rates.
In 2013, recurrent reports of diverse symptoms occurring in girls after receiving HPV vaccination appeared in Japanese media. The Ministry of Health, Labor and Welfare quickly responded by announcing a temporary suspension of its recommendation for the vaccine. The HPV vaccination rate soon fell to almost zero. In the present study, we calculated the potential future numbers of cervical cancer incidence and death that will be increased by this policy decision. We have assumed that the number of yearly vaccinations is evenly distributed across a daily basis. Future incidence and death increased in females born in FY2000 are estimated to be 3651 and 904, respectively, 4566 and 1130 for those born in FY2001, 4645 and 1150 for those born in FY2002, and 4657 and 1153 for those born in FY2003. In FY2020, the large increase of risks to females born in FY2004 amounts to 12.0 females per day who will now be at a higher risk for acquiring of cervical cancer in their future, and 3.0 females per day newly at risk for future death from that disease in its progressive form. No one should be able to accept this situation. We sincerely ask the government to resume its recommendation for the vaccine as soon as possible.
In Japan, recommendations for HPV vaccines were suspended in 2013 due to unfounded safety fears. Although vaccine opponents claim modifying sexual behavior can prevent cervical cancer, no comprehensive data exist on sexual behavior and the risk of high-grade cervical disease in a Japanese population. This study investigates sexual behavior and the risk of HPV infection and cervical disease in 3968 women aged 20–41 yrs undergoing cervical screening between April 2014 and March 2016. Mean age at first intercourse was 18.4 yrs ± 2.8 and 32% of women reported ≥ 6 lifetime sexual partners. In regression analyses, number of partners was a significant risk factor for HPV infection. However, for high-grade disease (CIN2+), when HPV genotype was adjusted for, number of partners was not statistically significant. The greatest risk factor was an HPV16/18 infection (adjusted odds ratio 113.7, 95% CI: 40.8–316.9). In conclusion, we found that having an HPV16/18 infection and not sexual behavior was the most significant risk factor for high grade cervical disease in young Japanese women. These infections can be prevented by a highly effective vaccine and we recommend that the Japanese government resume proactive recommendations for the HPV vaccine immediately.
Proactive recommendations for human papillomavirus (HPV) vaccines in Japan have been suspended. In this study, bivalent HPV vaccine is highly effective against HPV types 16 (HPV16) and 18, and significant cross-protection against HPV31, 45, and 52 was demonstrated. These findings should reassure politicians of vaccine effectiveness in a Japanese population.
The trend for cervical cancer in younger women has been increasing recently in Japan. However, as a result of the suspension of governmental recommendation, Japan's HPV (human papillomavirus) vaccination rate for girls born since 2000 has dropped sharply. We conducted an internet survey in December of 2019, 76 months after the suspension of recommendation, to verify the intention of mothers to inoculate their daughter under current circumstances and compared with our previous surveys and leaflet intervention effect. The rates of mothers who replied that they would "inoculate" were significantly higher at 9 and 23 months, but by 32 months after the suspension the rate was significantly lower (p < 0.05, p < 0.05, p < 0.05, respectively). The rates of the mothers who replied they would not inoculate were significantly lower at 9 months and 23 months, but at 76 months was significantly higher (p < 0.05, p < 0.05, p < 0.05, respectively). We found that intervention with a leaflet that could be used under the current suspension of the governmental recommendation did not increase the mothers' intention to inoculate their daughters. A leaflet that actively encourages vaccination may increase the intent of vaccination. It is strongly recommended that the MHLW promptly resume its recommendations for HPV vaccination.
Organized human papillomavirus vaccination (OHPV) in Japan was introduced in 2010 for girls aged 12–16 years who were born in 1994 or later. The rate of OHPV coverage was 70–80%. However, after suspension of the government vaccination recommendation, the coverage dramatically decreased. We aim to investigate the change in prevalence of HPV infection after the initiation of HPV vaccination. We recruited females aged 20–21 years attending public cervical cancer screening from 2014 to 2017 fiscal years (April 2014 to March 2018). Residual Pap test specimens were collected for HPV testing. We compared the prevalence of HPV type-specific infection between women registered in 2014 (born in 1993–1994, including the pre-OHPV generation) and registered in 2015–2017 (born in 1994–1997, the OHPV generation). We collected 2379 specimens. The vaccination coverage figures were 30.7%, 86.6%, 88.4% and 93.7% (p < 0.01) from 2014 to 2017, respectively. The prevalence of HPV16/18 infection significantly decreased from 1.3% in 2014 to 0% in 2017 (p = 0.02). The three most prevalent types were HPV52, 16 and 56 in 2014, and HPV52, 58 and 56 in 2015–2017, respectively. HPV16 and 33 infection rates decreased. On the other hand, the HPV58 infection rate was obviously increased after OHPV from 0.3% to 2.1%. Our study demonstrates that the prevalence of HPV16/18 infection dramatically decreased and the profile of type-specific HPV infection was changed after OHPV.
The Japanese government suspended proactive recommendations for the HPV vaccine in June 2013. The suspension is now in its seventh year, despite all the data pointing to the safety of the HPV vaccine. We reported a high vaccine effectiveness in the group of women vaccinated before their first intercourse (93.9%). The prevalence of cross-protected types of HPV 31/45/52 was also lower in the vaccinated group, and the vaccine effectiveness was 67.7%. Furthermore, prevalence of HPV16, 31 and 52 infection rates in the vaccinated group were obviously lower than that in the unvaccinated group, and no one had HPV18 or 45 infection in the vaccinated group. The addition of a cross-protective effect toward HPV types 31/45/52 to HPV types 16/18, which is the direct target of the bivalent HPV vaccine, may possibly prevent around 82% of invasive cervical cancer cases in Japan. With regard to the preventive effect of histological abnormalities, we also reported significant reduction in incidence of cervical intraepithelial neoplasia (CIN)3 or worse. Thus, the efficacy of the vaccine has been demonstrated for precancerous disease, and the diverse symptoms after HPV vaccination are likely functional somatic. For the future of Japanese girls, there is a need to resume the proactive recommendation of HPV vaccination and for immediate action to be taken by the Japanese government.
Abstract Background In Japan, new HPV immunizations have dropped dramatically after repeated adverse media reports and a June 2013 temporary suspension of the government's recommendation for the vaccine. The aim of the present study was to develop an efficient strategy to improve HPV immunization coverage across Japan. Methods We conducted an internet survey in Japan of mothers of 12–16 year-old girls who were unvaccinated as of May, 2015. The goal was to gather behavioral information from the mothers to develop a strategy for improving Japanese HPV immunization coverage. Results Valid survey answers were obtained from 2060 mothers. The survey found that a hypothetical restart of a governmental recommendation for the vaccine would induce 4.1 % of all the mothers surveyed to be more likely to encourage vaccination of their daughters, without any other preconditions. This initial result would be followed by a moderate spread of vaccinations to these daughters' close friends and acquaintances, hypothetically resulting in a total vaccination rate of 21.0 % of the targeted age-eligible girls. As a second critical step for improving vaccinations, an educational information sheet integrating the concepts of behavioral economics for changing behaviors was found to be significantly effective for persuading mothers with poorer decision-making facilities, who would otherwise prefer to wait to first see the vaccination of other girls of the same age as their daughter. Conclusions Following what we foresee as the inevitable restart of the Japanese government's recommendation for receiving the HPV vaccine, we expect to first see vaccinations occurring in a very small group of girls, the daughters of the most willing mothers, which will be roughly 4 % of those eligible for government paid vaccinations. This will be .
In Japan, the trend for cervical cancer at younger ages has been increasing. As a countermeasure, the HPV vaccine was introduced as a routine vaccination in April 2013. However, the Ministry of Health, Labour and Welfare (MHLW) announced a "Suspension of its active inoculation recommendation for HPV vaccine" in June 2013. In 2016, 32 months after that suspension, we conducted survey via Internet and compared the results with our previous ones conducted at 9 and 23 months after suspension (in 2014 and 2015, respectively). We examined the 'time-dependent change' of the 'intention of mothers to inoculate their daughters with the HPV vaccine' in terms of efficacy of external decision-making support. 17.5% of mothers in the first survey replied that they would inoculate their daughters under the current circumstances, 12.1% in the second survey, and 6.7% in the third, showing a consistent decrease in willingness over time (p = 0.03, p < 0.01). If the government recommendation were to be reintroduced, 22.5% of mothers in the first survey replied they would inoculate their daughters, 21.0% in the second survey, which indicated no significant difference (p = 0.65) over the first interval; however, this was significantly decreased to 12.2% in the third survey (p < 0.01). Our study revealed that the intention to inoculate their daughters has been declining among Japanese mothers over time triggered by the suspension.
Endometriosis is a heritable hormone-dependent gynecological disorder, associated with severe pelvic pain and reduced fertility; however, its molecular mechanisms remain largely unknown. Here we perform a meta-analysis of 11 genome-wide association case-control data sets, totalling 17,045 endometriosis cases and 191,596 controls. In addition to replicating previously reported loci, we identify five novel loci significantly associated with endometriosis risk (P<5 × 10−8), implicating genes involved in sex steroid hormone pathways (FN1, CCDC170, ESR1, SYNE1 and FSHB). Conditional analysis identified five secondary association signals, including two at the ESR1 locus, resulting in 19 independent single nucleotide polymorphisms (SNPs) robustly associated with endometriosis, which together explain up to 5.19% of variance in endometriosis. These results highlight novel variants in or near specific genes with important roles in sex steroid hormone signalling and function, and offer unique opportunities for more targeted functional research efforts. ; We acknowledge all the study participants in 11 individual endometriosis studies that provided an opportunity for the current study. We also thank many hospital directors and staff, gynaecologists, general practitioners and pathology services in Australia who provided assistance with confirmation of diagnoses. We would like to thank the research participants and employees of 23andMe for making this work possible. We thank the subjects of the Icelandic deCODE study for their participation. We thank research staff and clinicians for providing diagnostic confirmation for the OX data set. We would like to express our gratitude to the staff and members of the Biobank Japan and Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences for their outstanding assistance. The QIMR study was supported by grants from the National Health and Medical Research Council (NHMRC) of Australia (241,944, 339,462, 389,927, 389,875, 389,891, 389,892, 389,938, 443,036, 442,915, 442,981, 496,610, 496,739, 552,485, 552,498, 1,026,033 and 1,050,208), the Cooperative Research Centre for Discovery of Genes for Common Human Diseases (CRC), Cerylid Biosciences (Melbourne) and donations from N. Hawkins and S. Hawkins. Analyses of the QIMRHCS and OX GWAS were supported by the Wellcome Trust (WT084766/Z/08/Z) and makes use of WTCCC2 control data generated by the Wellcome Trust Case-Control Consortium (awards 076113 and 085475). The iPSYCH study was funded by The Lundbeck Foundation, Denmark (R102-A9118, R155-2014-1724 ), and the research has been conducted using the Danish National Biobank resource supported by the Novo Nordisk Foundation. A full list of the investigators who contributed to the generation of these data is available from http://www.wtccc.org.uk. D.R.N. was supported in part by the NHMRC Fellowship (613674) and ARC Future Fellowship (FT0991022) schemes. E.G.H. (631096) and G.W.M. (339446, 619667) were supported by the NHMRC Fellowships Scheme. S.M. is supported by an Australian Research Council Future Fellowship. A.P.M. was supported by a Wellcome Trust Senior Research Fellowship (award WT098017). N.R. was supported by funding from the Medical Research Council UK (MR/K011480/1). This study was funded by the BioBank Japan project, which is supported by the Ministry of Education, Culture, Sports, Sciences and Technology of Japanese government. ; Peer Reviewed
To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files ; Endometriosis is a heritable hormone-dependent gynecological disorder, associated with severe pelvic pain and reduced fertility; however, its molecular mechanisms remain largely unknown. Here we perform a meta-analysis of 11 genome-wide association case-control data sets, totalling 17,045 endometriosis cases and 191,596 controls. In addition to replicating previously reported loci, we identify five novel loci significantly associated with endometriosis risk (P<5 × 10(-8)), implicating genes involved in sex steroid hormone pathways (FN1, CCDC170, ESR1, SYNE1 and FSHB). Conditional analysis identified five secondary association signals, including two at the ESR1 locus, resulting in 19 independent single nucleotide polymorphisms (SNPs) robustly associated with endometriosis, which together explain up to 5.19% of variance in endometriosis. These results highlight novel variants in or near specific genes with important roles in sex steroid hormone signalling and function, and offer unique opportunities for more targeted functional research efforts. ; National Health and Medical Research Council (NHMRC) of Australia Cooperative Research Centre for Discovery of Genes for Common Human Diseases (CRC), Cerylid Biosciences (Melbourne) Wellcome Trust Wellcome Trust Case-Control Consortium Lundbeck Foundation, Denmark Novo Nordisk Foundation NHMRC ARC NHMRC Fellowships Scheme Australian Research Council Wellcome Trust Senior Research Fellowship Medical Research Council UK BioBank Japan project - Ministry of Education, Culture, Sports, Sciences and Technology of Japanese government
