Effectiveness of catch-up and routine program of the 9-valent vaccine on cervical cancer risk reduction in Japan.

In 2013, the national human papillomavirus (HPV) immunization program began. However, in June 2013, Japan's Ministry of Health, Labor and Welfare (MHLW) announced a "temporary" suspension of its recommendation for the human papillomavirus vaccine. Finally, in November 2021, the MHLW ended its suspension of the recommendation of the HPV vaccine. To address the 9-year gap in HPV vaccinations the suspension had caused, the MHLW conducted a program of catch-up vaccinations from April 2022 to March 2025. Finally, in April 2023, the 9-valent HPV vaccine was approved for both the routine and catch-up vaccination programs in Japan. In this study, we investigated the potential effects of the introduction of the 9-valent vaccine on the increased risk of cervical cancer in females born after fiscal year (FY) 2000. We estimated the lifetime relative risk of cervical cancer incidence and death using the improved routine and catch-up vaccination rates after the recent resumption of the governmental recommendation for women and girls to have the HPV vaccination. These relative risks were calculated using a lifetime risk of 1.000 for cervical cancer incidence and death for females born in FY 1993. We predicted that even if a 90% vaccination rate were to be achieved by FY 2024 with the 9-valent vaccine among women born between FY 2000 and FY 2005, the risk would remain higher than for the vaccination generation. Therefore, for women born between FY 2000 and FY 2005, it will be necessary to significantly improve the cervical cancer screening rate to compensate for this increased risk.

Disparities among Japanese municipalities in recommendations for routine and catch-up HPV vaccinations.

In November 2021, the government of Japan announced a reversal of its decision in 2013 to suspend the previous proactive recommendation for HPV vaccination. However, the program for young girls to receive routine and catch-up vaccinations has not necessarily developed as expected. We conducted a nationwide questionnaire survey by mail in September 2022. The survey was mailed to 133 municipalities consisting of all cities/wards of the Tokyo and Osaka Prefectures and all other prefectural capital cities. Responses were received from 82 municipalities (62.7%). Notification of routine HPV vaccinations had already been sent to 76 (92.7%) of the municipalities; 70 (85.4%) had been encouraged to promote catch-up vaccinations. The questionnaire forms for registration and pre-vaccination screening for routine immunization had been sent to 74.1% (60/81) of the municipalities and 68.8% (55/80) for catch-up immunizations. For catch-up vaccination, only 54 municipalities (65.9%) had detailed vaccination records for those eligible. In total, 10 municipalities (12.2%) had virtually no vaccination records because these had already been discarded. In addition, 61 municipalities (74.4%) had notified only women and girls eligible for a catch-up vaccination based on their vaccination record, whereas 25.6% (21/82) of the municipalities reported that they had sent, or would send, the notification to all women and girls within the targeted grades, including those who had already been vaccinated with three injections. The survey revealed disparities among the municipalities in their HPV vaccine notification processes. Future research on monitoring HPV vaccination rates and incidence rates of cervical cancer and precancerous lesions in each municipality will be desirable.

Intentions for catch-up HPV vaccination in Japan: an internet survey.

PURPOSE: In Japan, Japan's Ministry of Health, Labor, and Welfare decided to suspend govermental recommendation for HPV vaccination in FY 2013. The HPV vaccination rate for those born in FY 2000 or thereafter declined dramatically. In 2021, the "suspension of recommendation" ended. The catch-up vaccinations for the unvaccinated have been offered nationwide from FY 2022 to FY 2024. We aimed to quantify the vaccination intentions and characteristics of those young women now eligible for catch-up vaccination.  METHODS: In February of 2022, we conducted an internet survey targeted women who were born in 1997-2004 but who had not yet been HPV vaccinated. RESULTS: We received 1,648 valid responses. 41.6% of the respondents wanted to uptake the catch-up HPV vaccination, 29.7% were undecided, and 28.7% did not want to be vaccinated. The intention to uptake catch-up HPV vaccination was associated with a good history of gynecological visits, intention to receive cervical cancer screening, sexual activity, degree of anxiety about cervical cancer, familiarity with problems associated with cervical cancer, experience with vaccination recommendations, and knowledge about cervical cancer (p < 0.05, respectively). In the vaccinated generation, the proportion of the group that did not want to be vaccinated was significantly higher (p < 0.05). In the vaccine-suspended generation, the proportion of the group that wanted to be vaccinated was significantly higher (p < 0.05). CONCLUSION: Our survey revealed that catch-up vaccination intentions differed depending on the vaccination environment. It is necessary for all organizations involved with HPV vaccination, such as government, medical institutions, and educational institutions, to make recommendations based on an understanding of the characteristics of the "vaccinated generation" and the "vaccine-suspended generation".

Improved long-term survival of corpus cancer in Japan: A 40-year population-based analysis.

The incidence of uterine corpus cancer has been increasing globally due to increase in obesity. However, a detailed analysis of long-term epidemiological trends of corpus cancer in Japan, where obesity is relatively minimal, has not been conducted. In this retrospective, population-based study using the Osaka Cancer Registry, we analyzed 15 255 cases of corpus neoplasia registered between 1977 and 2016. We determined the age-standardized incidence, mortality, relative survival and conditional survival rates, and the treatment trends for corpus cancer over the last 40 years in Japan. The age-standardized incidence rate of corpus neoplasia increased sharply in 2000-2011 (APC = 9.9, 95% CI: 8.4-11.3), whereas the mortality rate trended to a much more modest increase (APC = 3.3, 95% CI: 2.7-3.8). Compared to 1977-2000, 10-year survival rates for post-2000 cases of localized and regional corpus cancers significantly improved (from 87.7% [95% CI: 85.8-89.4] to 94.2% [95% CI: 92.7-95.7] and from 47.5% [95% CI: 43.3-51.6] to 64.4% [95% CI: 61.0-67.6], respectively). This was largely associated with the significant increase in the percentage of localized and regional patients who received chemotherapy instead of radiation as an adjuvant therapy combined to surgery (P < .001 for both). We found that each histological type (endometrioid carcinoma, serous carcinoma, clear cell carcinoma and carcinosarcoma) has different characteristics of trend of age-standardized incidence rate, relative survival and distribution of extent of disease. In endometrioid carcinoma, the age-standardized incidence rate increased consistently after 1990, but the rate of increase was decreasing after 1997.

Effectiveness of human papillomavirus vaccine against cervical precancer in Japan: Multivariate analyses adjusted for sexual activity.

Japanese girls aged 12-16 years are offered free human papillomavirus (HPV) vaccination and cervical cancer screening is conducted with cytology and not HPV testing from the age of 20 years. So far, no study has analyzed the effect of HPV vaccination against cervical precancers considering HPV infection status and sexual activity. We aimed to analyze the vaccine effectiveness (VE) against HPV infection and cytological abnormalities, adjusted for sexual activity. This study comprised women aged 20-26 years who underwent cervical screening in Niigata. We obtained HPV vaccination status from municipal records and a questionnaire along with information concerning sexual activity. Of 5194 women registered for this study, final analyses included 3167 women in the vaccinated group (2821 vaccinated women prior to sexual debut) and 1386 women in the unvaccinated group. HPV 16/18 (0.2% vs 3.5%), 31/45/52 (3.4% vs 6.6%), and 31/33/45/52/58 (5.0% vs 9.3%) positive rates were significantly lower in the vaccinated group (P < 0.001). No women vaccinated before sexual debut had HPV 16/18-related cytological abnormalities. VE for HPV 16/18 infection and high-grade cytological abnormalities in women vaccinated prior to sexual debut were 95.8% (95% CI 81.9-99.0%; P < 0.001) and 78.3% (95% CI 11.3-94.7%; P = 0.033), respectively, in multivariate analyses adjusted for age and number of sexual partners. However, analyses of all vaccinated women did not show significant effectiveness against cytological abnormalities. Our results showed the effectiveness of HPV vaccine against high-grade cervical cytological abnormalities and the importance of the vaccination before sexual debut.

Long-term effectiveness of HPV vaccination against HPV infection in young Japanese women: Real-world data.

In Japan, public funding for HPV vaccination began in 2010 for girls aged 13-16 years (birth cohort years 1994-1997) and women born in 1994 who turned 25 in 2019. We aimed to verify the long-term effectiveness of the bivalent HPV vaccine in women aged 25 years. Subjects were women aged 25-26 years who underwent cervical cancer screening and HPV testing in Niigata from 2019 to 2020 (birth cohort years 1993-1994). Information on vaccination status and sexual behavior was obtained from a questionnaire and municipal records. We compared the HPV infection rates of the vaccinated and unvaccinated groups. Of the 429 registrants, 150 (35.0%) and 279 (65.0%) were vaccinated and unvaccinated, respectively. The average period from HPV vaccination to HPV testing was 102.7 months (8.6 years), with a median of 103 months (range 92-109 months). The HPV high-risk infection rate was 21.3% (32/150) in the vaccinated group and 23.7% (66/279) in the unvaccinated group (P = 0.63). The HPV16/18 infection rate was 0% (0/150) in the vaccinated group and 5.4% (15/279) in the unvaccinated group, showing a significant difference (P = 0.0018), and the vaccine effectiveness was 100%. The cross-protective type HPV31/45/52 infection rate in the vaccinated group was significantly lower than that in the unvaccinated group (3.3% vs. 10.0%, P = 0.013). There was no significant difference in the mean age at sexual debut and the number of previous sexual partners between the two groups. We have demonstrated the long-term 9-year effectiveness of the bivalent vaccine against HPV infection for the first time in Japan.

Change of HPV vaccination rates in Japan: the effect of individual notifications implemented by local governments.

BACKGROUND: In Japan, in June 2013, The Ministry of Health, Labor and Welfare (MHLW) decided to temporarily suspend its official recommendation for the participation of girls in the national immunization program. The HPV vaccination rate in Japan soon declined to below 1%. In October 2020, the MHLW notified that the municipalities could and should begin to individually notify girls and their parents targeted for routine vaccination. We have examined how that type of individual notification has affected the number of vaccinations. METHODS: From 12 municipalities (with a combined total population of approximately 4.06 million), we collected vaccination data for all girls who attended grades 6 through 10 from April 2019 to March 2021. We analyzed the number of initial-round vaccinations that occurred by month and the timing and the subjects of the individual notifications. RESULTS: The annual vaccination rate for tenth-grade students in 2020 in the six municipalities that had implemented individual notification was 9.46% (342/3618), which was significantly higher than the rate of 3.22% (54/1676) in the three municipalities that had not implemented individual notification (p < 0.001). On the other hand, the annual vaccination rate for the sixth to ninth-grade students in 2020 in the six municipalities that had implemented individual notification was not significantly (p = 0.56) higher than the rate in the three municipalities that did not: 1.43% (197/13,785) versus 1.33% (83/6260), respectively. CONCLUSION: This study clearly demonstrates the importance of providing information for routine vaccination directly to the targets and their parents.

The 'best friend effect': a promising tool to encourage HPV vaccination in Japan.

BACKGROUND: In Japan, HPV vaccination rates has dramaticaly declined since 2013. Since mothers are the ones making the decision to vaccinate their daughters against HPV, we probed the mothers' intention to receive vaccinations for themselves and to vaccinate their daughters against HPV, and their reasoning. METHODS: An internet survey was conducted in March of 2021. Through the screening, 1576 participants were extracted from a survey panel and divided into 3 groups based on their daughter's birth fiscal year (Group 1: 1994 to 1999, Group 2: 2000 to 2003, Group3: 2004 to 2008). The chi-square test and residual analysis were used for the statistical analysis of comparison among the groups. Logistic regression analysis was used to identify independent variables with mothers intention to get their daughters vaccinated under specific situations. RESULTS: The percentage of respondents without anxiety regarding their daughter's general vaccination was significantly higher in Group 1 (p < 0.05). In the mothers of daughters born in or after 2000 when vaccination rates declined (Groups 2 and 3), a situation in which 'The daughter's best friends were vaccinated before her' made the mothers think positively about HPV vaccination, and to the same degree as a situation in which 'You received a notice from your local government recommending vaccination' (Group 2: 41.6% (214/514) and 40.5% (208/514), Group 3: 48.5% (257/530) and 47.0% (249/530)). CONCLUSION: If mothers who have had their daughters vaccinated were to recommend HPV vaccination to their close friends, 'the best friend effect' should promote others to be vaccinated.

Development of information dissemination methods that contribute to improving maternal and child healthcare using social networking sites: a community-based cross-sectional study in Japan.

BACKGROUND: In recent years, feelings of isolation among mothers caring for small children has become a significant social issue in Japan. The purpose of this study is to develop a message to alleviate their loneliness, to evaluate the impact of social networking sites (SNS) for delivering such messages, and to propose means of more effective information transmission to promote health for mothers raising small children. METHODS: Our study was conducted in two stages, first an interview and then a cross-sectional study of the mothers involving a questionnaire survey. The interview was targeted two public-health nurses caring for mothers. Based on these interviews, we developed six messages intended to alleviate the mothers' sense of loneliness, which were vetted by seven mothers. The second stage was to conduct a questionnaire survey of mothers both before and after our selected message as advertisement on Instagram and analyzed the effect. The surveys were collected during routine child health check-ups in the City of Takatsuki, Japan. RESULTS: From the six draft messages created based on interviews with public health nurses, we selected the message that most relieves the feeling of loneliness of the mothers who are raising small children. The survey questionnaire was taken by 494 mothers prior to our posting of Instagram advertisements (ads), and afterwards by 419 mothers. The percentage of mothers feeling loneliness tended to decrease after reading the messages (before ads.:8.1%, after ads.:5.8%). 8.6% of the mothers (36/419) remembered seeing the Instagram ads. Mothers with financial anxiety were significantly more likely to have remembered seeing the Instagram ads (p < 0.01). CONCLUSIONS: Our results indicate that usefulness of SNS messaging for mothers raising small children may reduce their feeling of loneliness. Among the SNS, disseminating child-rearing information on Instagram may be more effective for people with financial instability.

Human papillomavirus vaccine to prevent cervical intraepithelial neoplasia in Japan: A nationwide case-control study.

Cervical cancer remains among the most common cancers in women worldwide and can be prevented by vaccination. The Ministry of Health, Labour and Welfare of Japan suspended active recommendation of regular human papillomavirus (HPV) vaccines in 2013 because of various symptoms including chronic pain and motor impairment. This nationwide case-control study from April 2013 to March 2017 targeted women aged 20-24 years old at cervical screening. We compared HPV vaccination exposure between those with abnormal and normal cytology. Abnormal cytology was classified based on the results of histological test and we calculated the odds ratio (OR) and 95% confidence interval (CI) of the above endpoints and vaccination exposure using the conditional logistic regression model and estimated vaccine effectiveness using the formula (1 - OR) × 100. A total of 2483 cases and 12 296 controls (one-to-five matching) were eligible in 31 municipalities in Japan. The distribution of histological abnormalities among cases was 797 CIN1 (including dysplasia) (32.1%), 165 CIN2 (6.7%), 44 CIN3 (1.8%), and eight squamous cell carcinoma (SCC) (0.3%). The OR of HPV vaccination compared with no vaccination for abnormal cytology, CIN1+, CIN2+, and CIN3+ versus controls was 0.42 (95% CI, 0.34-0.50), 0.42 (95% CI, 0.31-0.58), 0.25 (95% CI, 0.12-0.54), and 0.19 (95% CI, 0.03-1.15), respectively, equating to a vaccine effectiveness of 58.5%, 57.9%, 74.8%, and 80.9%, respectively. Eight patients had SCC, none was vaccinated. This nationwide case-control study in Japan demonstrated a substantial risk reduction in abnormal cytology and CIN among women who did versus those who did not receive HPV vaccination.

A nationwide birth year-by-year analysis of effectiveness of HPV vaccine in Japan.

In Japan, the age-adjusted incidence of cervical cancer has been increasing constantly and rapidly among younger women. We set out to accurately confirm the effectiveness of the HPV vaccine in Japan. Data were collected for women born in the fiscal year (FY) 1990 to 1997, who became eligible for their 20-y-old cervical cancer screening between the FY 2010 to 2017. The adjusted incidence of cervical intraepithelial neoplasia (CIN)1+ in women born in FY 1990 to 1993, that is those who reached the national vaccination target age prior to the introduction of publicly subsidized HPV vaccinations, referred here after as "the pre-introduction generation", was 1.42% (242/17 040). The incidence in the "vaccination generation" (women born in FY 1994 to 1997, that is those who were heavily vaccinated as a group when they were of the nationally targeted age of 13-16) was 1.66% (135/8020). There was no significant difference between these incidence rates. However, our FY birth year-by-year analysis revealed that the incidence of CIN1+ was obviously lower than that predicted based on just the trend for CIN1+ seen in the pre-introduction generation. Our analysis revealed that the incidence of CIN3+ was obviously lower in the vaccination generation than in the pre-introduction generation (P = .0008). The incidence of CIN was already tending to increase in both the pre-introduction and vaccination generations. The changes in CIN incidence by individual birth FY must be examined to accurately determine the actual effects of the HPV vaccine for reducing mild cervical lesions.

Updated Trends in Cancer in Japan: Incidence in 1985-2015 and Mortality in 1958-2018-A Sign of Decrease in Cancer Incidence.

BACKGROUND: Unlike many North American and European countries, Japan has observed a continuous increase in cancer incidence over the last few decades. We examined the most recent trends in population-based cancer incidence and mortality in Japan. METHODS: National cancer mortality data between 1958 and 2018 were obtained from published vital statistics. Cancer incidence data between 1985 and 2015 were obtained from high-quality population-based cancer registries maintained by three prefectures (Yamagata, Fukui, and Nagasaki). Trends in age-standardized rates (ASR) were examined using Joinpoint regression analysis. RESULTS: For males, all-cancer incidence increased between 1985 and 1996 (annual percent change [APC] +1.1%; 95% confidence interval [CI], 0.7-1.5%), increased again in 2000-2010 (+1.3%; 95% CI, 0.9-1.8%), and then decreased until 2015 (-1.4%; 95% CI, -2.5 to -0.3%). For females, all-cancer incidence increased until 2010 (+0.8%; 95% CI, 0.6-0.9% in 1985-2004 and +2.4%; 95% CI, 1.3-3.4% in 2004-2010), and stabilized thereafter until 2015. The post-2000 increase was mainly attributable to prostate in males and breast in females, which slowed or levelled during the first decade of the 2000s. After a sustained increase, all-cancer mortality for males decreased in 1996-2013 (-1.6%; 95% CI, -1.6 to -1.5%) and accelerated thereafter until 2018 (-2.5%; 95% CI, -2.9 to -2.0%). All-cancer mortality for females decreased intermittently throughout the observation period, with the most recent APC of -1.0% (95% CI, -1.1 to -0.9%) in 2003-2018. The recent decreases in mortality in both sexes, and in incidence in males, were mainly attributable to stomach, liver, and male lung cancers. CONCLUSION: The ASR of all-cancer incidence began decreasing significantly in males and levelled off in females in 2010.

A questionnaire survey on a feeling of loneliness of the mothers raising children.

AIM: A feeling of isolation childcare mothers' face is a serious social problem in Japan because the relationships with mothers and local communities have grown sparser. The purpose of this study was to clarify the feelings of isolation of mothers during childcare and the factors related to it. METHODS: We conducted a questionnaire survey in Yao City, Osaka. We mailed out a questionnaire survey of 1293 mothers with infants who had either a 4-month or 42-month routine health checkup during the period from September to December of 2018. RESULTS: There was no association between "feeling lonely while raising my child" and the absence of "people who helped raise my children." On the other hand, it was found that the mothers' inner feelings, such as "I wasn't satisfied with my childcare environment" (OR: 2.55, 95% CI: 1.32-4.91, p = 0.0052) or "I lacked confidence in my own childcare abilities" (OR: 6.21, 95% CI: 4.31-8.95, p < 0.0001), were associated with their sense of loneliness. CONCLUSIONS: Mothers' "sense of loneliness" was shown to be best correlated with their dissatisfaction with the environment of their childcare and with their lack of confidence in raising their own children.

Corrected human papillomavirus vaccination rates for each birth fiscal year in Japan.

In Japan, the serious adverse events after human papillomavirus (HPV) vaccination were widely reported in the media. The Ministry of Health, Labour and Welfare of Japan (MHLW) announced the suspension of the governmental recommendation of HPV vaccine in 2013, and the inoculation rate has since sharply declined. The estimated inoculation rate for each birth fiscal year (FY) announced by the MHLW and the actual numbers for each birth FY surveyed by local governments were very different. In particular, the cumulative vaccination rate of girls born in FY2000 was regarded to be as high as 42.9% by the Council of the MHLW. However, this estimation included a confusion. When the suspension of the governmental recommendation was announced in FY2013, the girls born in FY2000 turned 13 years old, the targeted starting age of the HPV vaccination. The vaccination rate of this generation is considered to be quite low. The numbers were recalculated in this study. This study revealed that the real vaccination rate is only 14.3%. Female individuals born in or after FY2000 have been confirmed to be exposed to the same cervical cancer risk as before the HPV vaccine was introduced in Japan.

Differences in Coronavirus disease - 19 vaccination related side effects in patients with ulcerative colitis and Crohn's disease in Japan.

BACKGROUND/PURPOSE OF THIS STUDY: It has been recommended that individuals with inflammatory bowel disease (IBD) be vaccinated against Coronavirus disease - 19 (COVID-19). Recently, we documented the incidence of side effects (SEs) after COVID-19 immunization among individuals with IBD in Japan. However, the study did not show differences between the types of IBD or the patients' clinical backgrounds. In this survey, we aimed at investigating whether the frequency of SEs differed among patients with IBD. METHODS: A cross-sectional survey was conducted among adult patients with IBD at Kobe University between March 2022 and September 2022. RESULTS: Total 195 patients, including 134 with ulcerative colitis (UC) and 61 with Crohn's disease (CD), completed the questionnaire and were included in the analysis. Of these, 92.3%, 91.3% and 44.1% received the initial, second and third dose of the COVID-19 vaccine, respectively. The frequency of local symptoms following the initial, second and third dose of the vaccine was comparable between patients with UC and CD (69.6% vs. 72.7%, 64.2% vs. 69.1% and 63.5% vs. 73.9%, respectively). Muscle pain after the initial and second doses of the COVID-19 vaccine was more common among patients treated with corticosteroids (58.1% vs. 37.6% and 60.0% vs. 31.8%, p < 0.05). Female sex, younger age and current or former smoking were associated with an increased incidence of fever or chills after the initial dose of the vaccine (p < 0.05). In contrast, corticosteroid use was identified as a factor associated with an increased incidence of muscle pain after the initial dose of vaccine (p < 0.05). CONCLUSION: The use of corticosteroids could increase the risk of muscle pain following COVID-19 vaccination. Additionally, factors such as female sex, younger age and current or former smoking can affect the incidence of fever or chills. This information should encourage patients with IBD to get vaccinated against COVID-19.

Disseminated Mycobacterium avium Complex Infection in a Patient Treated With Immunosuppressants.

Mycobacterium avium complex (MAC) is an important cause of opportunistic infections in immunosuppressed hosts, such as patients with HIV infection and solid organ transplant recipients. MAC disease usually presents in 4 distinct clinical categories: chronic pulmonary disease, disseminated disease, skin/soft-tissue infection, and superficial lymphadenitis. However, clinical reports on gastrointestinal (GI) MAC disease are rare, especially in patients without HIV infection or a history of organ transplantation. We describe a case of non-HIV-associated GI MAC disease in a patient with long-term mycophenolate mofetil use. In this case, MAC organisms in the GI tract and ascites were observed. Endoscopy revealed a unique colonic image with large, deep epithelial denudations. This suggests that apart from patients with HIV infection or transplant recipients, those treated with immunosuppressants can have disseminated MAC. Therefore, internal physicians need to monitor patients undergoing mycophenolate mofetil immunosuppressant therapy.

Genotype prevalence and age distribution of human papillomavirus from infection to cervical cancer in Japanese women: A systematic review and meta-analysis.

BACKGROUND: National HPV vaccination coverage in Japan is less than one percent of the eligible population and cervical cancer incidence and mortality are increasing. This systematic review and meta-analysis aimed to provide a comprehensive estimate of HPV genotype prevalence for Japan. METHODS: English and Japanese databases were searched to March 2021 for research reporting HPV genotypes in cytology and histology samples from Japanese women. Summary estimates were calculated by disease stage from cytology only assessment - Normal, ASCUS, LSIL, HSIL and from histological assessment - CIN1, CIN2, CIN3/AIS, ICC (ICC-SCC, and ICC-ADC), and other. A random-effects meta-analysis was used to calculate summary prevalence estimates of any-HPV, high-risk (HR) and low-risk (LR) vaccine types, and vaccine genotypes (bivalent, quadrivalent, or nonavalent). This study was registered with PROSPERO: CRD42018117596. RESULTS: A total of 57759 women with normal cytology, 1766 ASCUS, 3764 LSIL, 2017 HSIL, 3130 CIN1, 1219 CIN2, 869 CIN3/AIS, and 4306 ICC (which included 1032 ICC-SCC, and 638 ICC-ADC) were tested for HPV. The summary estimate of any-HPV genotype in women with normal cytology was 15·6% (95% CI: 12·3-19·4) and in invasive cervical cancer (ICC) was 85·6% (80·7-89·8). The prevalence of HR-HPV was 86·0% (95% CI: 73·9-94·9) for cytological cases of HSIL, 76·9% (52·1-94·7) for histological cases of CIN3/AIS, and 75·7% (68·0-82·6) for ICC. In women with ICC, the summary prevalence of bivalent vaccine genotypes was 58·5% (95% CI: 52·1-64·9), for quadrivalent genotypes was 58·6% (52·2-64·9) and for nonavalent genotypes was 71·5% (64·9-77·6), and of ICC cases that were HPV positive over 90% of infections are nonavalent vaccine preventable. There was considerable heterogeneity in all HPV summary estimates and for ICC, this heterogeneity was not explained by variability in study design, sample type, HPV assay type, or HPV DNA detection method, although studies published in the 1990s had lower prevalence estimates of any-HPV and HR HPV genotypes. INTERPRETATIONS: HPV prevalence is high among Japanese women. The nonavalent vaccine is likely to have the greatest impact on reducing cervical cancer incidence and mortality in Japan.

Long-Term Effects of Human Papillomavirus Vaccination in Clinical Trials and Real-World Data: A Systematic Review.

The preventive effect of HPV vaccines against anogenital and oropharyngeal cancers has been proven in both clinical trials and real-world data. We reviewed the published evidence about the long-term efficacy and effectiveness of the HPV vaccine in available papers of clinical trials and real-world data. As far as we searched, the longest period of preventive effect for the bivalent, 4-valent, and 9-valent vaccine were 11 years in the Costa Rica trial, 14 years in the FUTURE II, and 8 years in the LTFU extension study of V503-002 and the Scandinavian study, respectively. The sustained clinical effect during the observation period was longest for the 4-valent vaccine. In real-world data, the longest observation period of the vaccine effectiveness was 12 years in an Australian study for the 4-valent vaccine. On the other hand, the longest period of long-term persistence of HPV vaccine-induced seropositivity was 14 years in FUTURE II for the 4-valent vaccine. For the bivalent vaccine, additional long-term follow-up studies may not have been planned due to the launch of the 4-valent and 9-valent vaccines. In some studies of the 9-valent vaccine, the results have not yet been published because of the short observation period. The additional results are expected in the future. In a national immunization program, most girls and boys are inoculated with HPV vaccine by the time puberty begins; thus, it is important to monitor the vaccine effect at least until the sexually active period in their 20s and 30s.

Can Catch-Up Vaccinations Fill the Void Left by Suspension of the Governmental Recommendation of HPV Vaccine in Japan?

In 2013, the Ministry of Health, Labor, and Welfare (MHLW) in Japan announced a suspension of the governmental recommendation for routine HPV vaccinations. In 2020, MHLW started individual notifications of HPV vaccine to the targeted girls. In April 2022, the governmental recommendation was restarted, and catch-up vaccinations started. We evaluated the benefits and limitations of the MHLW's new vaccination strategies by estimating the lifetime risk for cervical cancer for each birth FY under different scenarios to suggest a measure for the vaccine suspension generation. It was revealed that catch-up immunization coverage among the unvaccinated must reach as high as 90% in FY2022, when the program begins, in order to reduce the risk of the females already over the targeted ages to the same level or lower than that of women born in FY1994-1999 who had high HPV vaccination rates. For women whose vaccination coverage waned because of their birth FYs, strong recommendations for cervical cancer screening should be implemented.