Risk of COVID-19 death for people with a pre-existing cancer diagnosis prior to COVID-19-vaccination: A systematic review and meta-analysis.

While previous reviews found a positive association between pre-existing cancer diagnosis and COVID-19-related death, most early studies did not distinguish long-term cancer survivors from those recently diagnosed/treated, nor adjust for important confounders including age. We aimed to consolidate higher-quality evidence on risk of COVID-19-related death for people with recent/active cancer (compared to people without) in the pre-COVID-19-vaccination period. We searched the WHO COVID-19 Global Research Database (20 December 2021), and Medline and Embase (10 May 2023). We included studies adjusting for age and sex, and providing details of cancer status. Risk-of-bias assessment was based on the Newcastle-Ottawa Scale. Pooled adjusted odds or risk ratios (aORs, aRRs) or hazard ratios (aHRs) and 95% confidence intervals (95% CIs) were calculated using generic inverse-variance random-effects models. Random-effects meta-regressions were used to assess associations between effect estimates and time since cancer diagnosis/treatment. Of 23 773 unique title/abstract records, 39 studies were eligible for inclusion (2 low, 17 moderate, 20 high risk of bias). Risk of COVID-19-related death was higher for people with active or recently diagnosed/treated cancer (general population: aOR = 1.48, 95% CI: 1.36-1.61, I2 = 0; people with COVID-19: aOR = 1.58, 95% CI: 1.41-1.77, I2 = 0.58; inpatients with COVID-19: aOR = 1.66, 95% CI: 1.34-2.06, I2 = 0.98). Risks were more elevated for lung (general population: aOR = 3.4, 95% CI: 2.4-4.7) and hematological cancers (general population: aOR = 2.13, 95% CI: 1.68-2.68, I2 = 0.43), and for metastatic cancers. Meta-regression suggested risk of COVID-19-related death decreased with time since diagnosis/treatment, for example, for any/solid cancers, fitted aOR = 1.55 (95% CI: 1.37-1.75) at 1 year and aOR = 0.98 (95% CI: 0.80-1.20) at 5 years post-cancer diagnosis/treatment. In conclusion, before COVID-19-vaccination, risk of COVID-19-related death was higher for people with recent cancer, with risk depending on cancer type and time since diagnosis/treatment.

Temporal evolution of suicide by levels of rurality and deprivation among Japanese adults aged 20 years or over between 2009 and 2022.

PURPOSE: Previous studies have reported that levels of rurality and deprivation are factors associated with suicide risk. Reports on the association between rurality, deprivation and suicide incidence during the COVID-19 pandemic are scarce. The study aims to investigate how suicide rates evolved in areas with different levels of rurality and deprivation among Japanese adults aged 20 years or older between 2009 and 2022. METHODS: This study used population density in 2020 as an indicator of rurality and per capita prefectural income in 2019 as a proxy for deprivation in Japan's 47 prefectures. Joinpoint regression analysis was performed to analyze secular trends in suicide rates by rurality and deprivation. RESULTS: Suicide rates for both men and women at different levels of rurality and deprivation remained roughly parallel during the research period. Suicide rates for men and women at all levels of rurality and deprivation were on a downward trend until around 2019, just before the onset of the pandemic. Following this, suicide rates in women showed a clear upward trend, while the trend in suicide rates for men also changed around 2019, with a slightly increasing or flat trend thereafter. Changes in suicide rates were greater among women and those aged 20-59 years. CONCLUSIONS: In Japan, time trends in suicide rates for both men and women have changed before and after the pandemic, but levels of rurality and deprivation across the 47 prefectures do not appear to have contributed much to these changes.

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.

Impact of disruptions and recovery for established cervical screening programs across a range of high-income country program designs, using COVID-19 as an example: A modelled analysis.

COVID-19 has disrupted cervical screening in several countries, due to a range of policy-, health-service and participant-related factors. Using three well-established models of cervical cancer natural history adapted to simulate screening across four countries, we compared the impact of a range of standardised screening disruption scenarios in four countries that vary in their cervical cancer prevention programs. All scenarios assumed a 6- or 12-month disruption followed by a rapid catch-up of missed screens. Cervical screening disruptions could increase cervical cancer cases by up to 5-6%. In all settings, more than 60% of the excess cancer burden due to disruptions are likely to have occurred in women aged less than 50 years in 2020, including settings where women in their 30s have previously been offered HPV vaccination. Approximately 15-30% of cancers predicted to result from disruptions could be prevented by maintaining colposcopy and precancer treatment services during any disruption period. Disruptions to primary screening had greater adverse effects in situations where women due to attend for screening in 2020 had cytology (vs. HPV) as their previous primary test. Rapid catch-up would dramatically increase demand for HPV tests in 2021, which it may not be feasible to meet because of competing demands on the testing machines and reagents due to COVID tests. These findings can inform future prioritisation strategies for catch-up that balance potential constraints on resourcing with clinical need.

Geography of suicide in Japan: spatial patterning and rural-urban differences.

PURPOSE: There are notable geographic variations in incidence rates of suicide both in Japan and globally. Previous studies have found that rurality/urbanity shapes intra-regional differences in suicide mortality, and suicide risk associated with rurality can vary significantly by gender and age. This study aimed to examine spatial patterning of and rural-urban differences in suicide mortality by gender and age group across 1887 municipalities in Japan between 2009 and 2017. METHODS: Suicide data were obtained from suicide statistics of the Ministry of Health, Labour and Welfare in Japan. We estimated smoothed standardized mortality ratios for suicide for each of the municipalities and investigated associations with level of rurality/urbanity using Bayesian hierarchical models before and after adjusting for socioeconomic characteristics. RESULTS: The results of the multivariate analyses showed that, for males aged 0-39 and 40-59 years, rural residents tended to have a higher suicide risk compared to urban ones. For males aged 60+ years, a distinct rural-urban gradient in suicide risk was not observed. For females aged 0-39 years, a significant association between suicide risk and rurality was not observed, while for females aged 40-59 years and females aged 60 years or above, the association was a U-shaped curve. CONCLUSION: Our results showed that geographical distribution of and rural-urban differences in suicide mortality in Japan differed substantially by gender and age. These findings suggest that it is important to take demographic factors into consideration when municipalities allocate resources for suicide prevention.

[A feasibility study on cervical screening in non-attenders invited to undergo HPV self-sampling with cytology triage versus repeat invitation for cytology screening in Hokkaido].

Objectives　We investigated the participation and detection rates of cervical lesions in cervical screening non-attenders offered HPV (human papillomavirus) self-sampling with cytology triage.Methods　From 2016 to 2018, HPV self-sampling was routinely offered as an option, along with cytology, to all non-attenders in Ebetsu City, Japan. The primary endpoints were ≥CIN2 and ≥CIN3 detection rates, and secondary endpoints were abnormal cytology rates and follow-up compliance.Results　Overall, recall invitations were mailed to 6,116 non-attenders, with a response rate of 15.9% (cytology: 6.5%, HPV testing: 9.4%). Of the responders to undergo HPV self-sampling, 11.7% had a positive result and were referred to cytology triage. Moreover, ≥CIN2 and ≥CIN3 detection rates were 1.7% and 0.9%, respectively, in the HPV self-sampling group, and 1.0% and 0.8%, respectively, in the cytology group, showing no statistically significant differences. In those who underwent cytology triage following an HPV positive test, ≥CIN2 and ≥CIN3 detection rates were 23.8% and 11.9%, respectively, which was significantly higher than those who only underwent cytology alone.Conclusion　HPV self-sampling followed by cytology triage is highly effective at detecting high grade disease in non-attenders. Thus, multi-municipality-based studies to standardize processes involving this method are warranted. Furthermore, HPV self-sampling could be a promising method for inviting non-attenders who have difficulty undergoing cervical screening in the COVID-19 pandemic era.

Bivalent Human Papillomavirus Vaccine Effectiveness in a Japanese Population: High Vaccine-Type-Specific Effectiveness and Evidence of Cross-Protection.

Background: Proactive recommendations for human papillomavirus (HPV) vaccines in Japan have been suspended for 5 years because of safety concerns. While no scientific evidence exists to substantiate these concerns, one reason given for not reinstating recommendations is the lack of reliable vaccine effectiveness (VE) data in a Japanese population. This study reports the VE of the bivalent HPV vaccine in Japanese women aged 20-22 years. Methods: During cervical screening between 2014 and 2016, women had Papanicolaou smears and HPV tests performed and provided data about their sexual history. Estimates of VE for vaccine-targeted HPV type 16 (HPV16) and 18 and cross-protection against other types were calculated. Results: Overall, 2197 women were tested, and 1814 were included in the analysis. Of these, 1355 (74.6%) were vaccinated, and 1295 (95.5%) completed the 3-dose schedule. In women sexually naive at vaccination, the pooled VEs against HPV16 and 18 and for HPV31, 45, and 52 were 95.5% (P < .01) and 71.9% (P < .01), respectively. When adjusted for number of sex partners and birth year, pooled VEs were 93.9% (P = .01) and 67.7% (P = .01) for HPV16 and 18 and HPV31, 45, and 52, respectively. Conclusions: The bivalent HPV vaccine is highly effective against HPV16 and 18. Furthermore, significant cross-protection against HPV31, 45, and 52 was demonstrated and sustained up to 6 years after vaccination. These findings should reassure politicians about the VE of bivalent HPV vaccine in a Japanese population.

Comparison of human papillomavirus genotyping and cytology triage, COMPACT Study: Design, methods and baseline results in 14 642 women.

Although cytology-based screening programs have significantly reduced mortality and morbidity from cervical cancer, the global consensus is that primary human papillomavirus (HPV) testing for cervical screening increases detection of high-grade cervical intraepithelial neoplasia (CIN) and invasive cancer. However, the optimal triage strategy for HPV-positive women to avoid over-referral to colposcopy may be setting specific. As Japan requires data that have been generated domestically to modify screening guidelines, we conducted a 3-year prospective study, COMparison of HPV genotyping And Cytology Triage (COMPACT), to evaluate the potential role of HPV16/18 partial genotyping and cytology for primary HPV screening. In total, 14 642 women aged 20 to 69 years undergoing routine screening at 3 centers in Hokkaido were enrolled. Conventional cytology and HPV testing were carried out. Women with abnormal cytology or HPV16/18 positivity underwent colposcopy. Those with 12 other high-risk (hr) HPV types underwent repeat cytology after 6 months. Primary study endpoints were detection of high-grade cervical disease defined as CIN2/CIN3 or greater as determined by consensus pathology. Prevalence of cytological abnormalities was 2.4%. hrHPV, HPV 16, and HPV 18 were detected in 4.6%, 0.9%, and 0.3% of women, respectively. HPV16/18 were detected in all (8/8) invasive cervical cancers and in all (2/2) adenocarcinomas in situ. Both cytological abnormalities and hrHPV positivity declined with increasing age. This is the first Japanese study to investigate the role of partial genotyping and cytology in an HPV-based screening program. Results should help policy-makers develop guidelines for future cervical screening programs and management of cervical abnormalities based on HPV genotype.

Job Stress Factors Affect Workplace Resignation and Burnout among Japanese Rural Physicians.

Shortage of healthcare workers is a global problem. It is important to clarify factors, including job stress, that influence workplace resignation and factors that cause burnout among rural physicians. The study was designed as a cross-sectional questionnaire survey. We sent questionnaires to town or village hospitals and clinics (n = 1,898) in Hokkaido, Tohoku, Shikoku, and Kyushu and Okinawa. The number of participants was 509. Of these 7.7% were female and 21.6% were < 50 years. Internal or general medicine physicians were asked about personal and job factors, job stress based on the demand-control-support model, intention to resign from current position, and burnout evaluated using the Maslach Burnout Inventory-General Survey. Overall, 10.4% of the participants intended to resign, and 21.8% was defined as burnout positive. In the multivariate logistic regression analysis, dissatisfaction with income (OR, 3.63; 95% CI, 1.63-8.10), having one's hometown in another town or village in the same prefecture (OR, 3.53; 95% CI, 1.18-10.62) were significantly related to intention to resign, while high job control (OR, 0.72; 95% CI, 0.58-0.88) had a significantly protective effect. In the multivariate analysis, high job demand (OR, 1.48; 95% CI, 1.28-1.72) was significantly related to burnout, and high job control (OR, 0.66; 95% CI, 0.55-0.78) and high support from co-workers (OR 0.88, 95% CI, 0.78-1.00) had a significantly protective effect. Improving job stress factors, especially job control, and taking into consideration physicians' hometown and income may be important factors to prevent resignation from a current position and burnout among Japanese rural physicians.

Social support and its interrelationships with demand-control model factors on presenteeism and absenteeism in Japanese civil servants.

OBJECTIVES: To elucidate the impact of social support and its interrelations with other demand-control-support (DCS) model factors on presenteeism and absenteeism, and to determine which DCS factors were most influential. METHODS: Questionnaires from 2535 local government employees were analyzed. The Brief Job Stress Questionnaire (BJSQ) was used to assess DCS factors including job demand, job control, and social support from supervisors and coworkers. The Stanford Presenteeism Scale 13-item version (SPS-13) was used to evaluate both absenteeism (absent days) and presenteeism. For the latter, the Work Impairment Score (WIS) and the Work Output Score (WOS) were also used. Possible confounder-adjusted logistic and negative binomial regression analyses were performed to obtain odds ratios (ORs) for WIS and WOS and relative risks (RRs) for absenteeism according to DCS factors. RESULTS: Higher job control had a significantly protective effect on higher WIS in both males and females and a lower WOS in males. Based on a point estimate of an OR per 1 standard deviation change of each DCS factor, job control had the strongest effect on higher WIS in both males and females and a lower WOS in males. Higher job demand resulted in significantly higher ORs for both male and female WIS, and a lower WOS in females. Support from supervisors had a significantly protective effect on higher WIS in females and a lower WOS in males. Support from coworkers had a significantly protective effect on higher WIS in males. Higher support from coworkers had a significantly protective effect on absenteeism among both males and females, and higher job control had a significantly protective effect in females. The combination of high job strain and low support from supervisors had a significantly worsening effect, except for absenteeism in females. High job strain and low support from coworkers had a significantly worsening effect except for WOS in males. CONCLUSIONS: The results suggest job control was the DCS factor most related to presenteeism. Higher support from supervisors and coworkers had a protective effect on presenteeism, and higher job demand had a worsening effect. Higher support from coworkers had a protective effect on absenteeism among both males and females. Interventions should focus on improving job control as a possible countermeasure to presenteeism, and encouraging support from coworkers as a possible countermeasure to absenteeism.

[Effects of prenatal yoga: a systematic review of randomized controlled trials].

OBJECTIVES: While several studies on the preventive and therapeutic effects of prenatal yoga (maternity yoga) have been reported in recent years, there has been no systematic review on the effects of prenatal yoga based on randomized controlled trials (RCT). The purpose of this study, therefore, was to systematically review the literature to clarify the effects of prenatal yoga in RCT focusing on the contents of the intervention, the intervention means, and the frequency of practice. METHODS: The literature search was performed using the electronic database, PubMed. The inclusion criteria were RCT, pregnant women, and yoga intervention. RESULTS: In total, 54 citations were found; of these, eight studies (10 reports) were included in the final analysis. In four studies on healthy pregnant women, significant improvement in pain and pleasure at delivery, duration of delivery, perceived stress levels during pregnancy, anxiety levels, depression, pregnancy-related experiences, quality of life, and interpersonal relationships were compared to those in the control group. In two studies on depressed pregnant women, one reported that depression, anxiety levels, anger levels, leg pain, and back pain significantly improved with yoga, while the other found no differences from the control group. In one study of high-risk pregnant women with morbidity factors such as obesity or advanced age, yoga resulted in significantly fewer cases of pregnancy-induced hypertension, gestational diabetes, and intrauterine growth restriction, as well as a decrease in perceived stress levels. In one study on pregnant women with pelvic pain, the median pain score was lower in the yoga group. Regarding the contents of the intervention, while the two studies for depressed pregnant women only included physical postures, the remaining six studies also included breathing technique and meditation. Interventions were performed using lectures by instructors alone or together with self-teaching. The frequency of the intervention varied within each study. CONCLUSION: The findings suggest that prenatal yoga may help reduce pelvic pain. It may also improve mental condition (stress, depression, anxiety, etc.), physical condition (pain and pleasure at the delivery, etc.), and perinatal outcomes (obstetrical complications, delivery time, etc.). However, further studies are needed. The contents of the intervention, the intervention means, and the frequency varied with each study. Thus, it is necessary to further examine the content of effective interventions, intervention means, and frequency that suit participant's characteristics and each outcome. Further research in this field, particularly randomized controlled trials, is merited.

Epidemic of charcoal burning suicide in Japan.

BACKGROUND: The charcoal burning suicide epidemics in both Hong Kong and Taiwan have been well documented. However, little is known about the situation in Japan. AIMS: To examine the impact of charcoal burning suicide on the overall and other method-specific suicide rates between 1998 and 2007 in Japan. METHOD: Using data obtained from the Vital Statistics of Japan, negative binomial regression analyses were performed to investigate the impact of the charcoal burning method. RESULTS: In males and females aged 15-24 and 25-44 years, the charcoal burning epidemic led to a substantial increase in overall suicides, without a decrease in other methods. In all other age groups, no such trend was observed. CONCLUSIONS: In young Japanese, the charcoal burning method may have appealed to individuals who might not have chosen other highly or relatively lethal methods, and consequently led to an increase in overall suicides.

Incidence risk of cervical intraepithelial neoplasia 3 or more severe lesions is a function of human papillomavirus genotypes and severity of cytological and histological abnormalities in adult Japanese women.

We examined incidence probabilities of cervical intraepithelial neoplasia 3 (CIN3) or more severe lesions (CIN3+) in 1,467 adult Japanese women with abnormal cytology in relation to seven common human papillomavirus (HPV) infections (16/18/31/33/35/52/58) between April 2000 and March 2008. Sixty-seven patients with multiple HPV infection were excluded from the risk factor analysis. Incidence of CIN3+ in 1,400 patients including 68 with ASCUS, 969 with low grade squamous intraepithelial lesion (LSIL), 132 with HSIL without histology-proven CIN2 (HSIL/CIN2(-)) and 231 with HSIL with histology-proven CIN2 (HSIL/CIN2(+)) was investigated. In both high grade squamous intraepithelial lesion (HSIL)/CIN2(-) and HSIL/CIN2(+), HPV16/18/33 was associated with a significantly earlier and higher incidence of CIN3+ than HPV31/35/52/58 (p = 0.049 and p = 0.0060, respectively). This association was also observed in LSIL (p = 0.0002). The 1-year cumulative incidence rate (CIR) of CIN3+ in HSIL/CIN2(-) and HSIL/CIN2(+) according to HPV genotypes (16/18/33 vs. 31/35/52/58) were 27.1% vs. 7.5% and 46.6% vs. 19.2%, respectively. In contrast, progression of HSIL/CIN2(+) to CIN3+ was infrequent when HPV DNA was undetected: 0% of 1-year CIR and 8.1% of 5-year CIR. All cervical cancer occurred in HSIL cases of seven high-risk HPVs (11/198) but not in cases of other HPV or undetectable/negative-HPV (0/165) (p = 0.0013). In conclusion, incidence of CIN3+ depends on HPV genotypes, severity of cytological abnormalities and histology of CIN2. HSIL/CIN2(+) associated with HPV16/18/33 may justify early therapeutic intervention, while HSIL/CIN2(-) harboring these HPV genotypes needs close observation to detect incidence of CIN3+. A therapeutic intervention is not indicated for CIN2 without HPV DNA.

Impact of the COVID-19 pandemic on suicide rates in Japan through December 2021: An interrupted time series analysis.

Background: The COVID-19 pandemic is negatively impacting mental health globally. While increased social cohesion may have initially decreased suicide risk, there are few reports on the long-term impact. We examined the impact of the pandemic on suicide by gender and age through December 2021 in Japan. Methods: We analyzed trends in monthly suicide rates by age and gender from January 2016 to December 2021 using provisional mortality data in an interrupted time series analysis. We also considered linear trends in the pre-pandemic period and seasonal variations. Pandemic onset was defined as from April 2020. Estimated excess deaths by suicide that occurred during the pandemic were calculated. Findings: Excess number of suicide deaths during the pandemic period was estimated to be 1208 for men and 1825 for women. While there was no statistically significant increase in suicide rates overall for both men and women during the pandemic compared to the pre-pandemic, age-specific analyses showed a statistically significant increase in men 20-29 and 40-49 years, and in women of all age groups, except those under 20, 40-49 and over 80 years. Interpretation: The COVID-19 pandemic has had a negative impact on suicide rates in Japan and the impact is most pronounced in women and younger age groups. Subgroup analyses are needed, with a particular focus on those considered to be vulnerable and at increased suicide risk. Funding: A Grant-in-Aid for scientific research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (Award Number 21K10462).

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.

Impact of prenatal exposure to mercury and selenium on neurodevelopmental delay in children in the Japan environment and Children's study using the ASQ-3 questionnaire: A prospective birth cohort.

Neurodevelopmental delay is associated with neurodevelopmental disorders. Prenatal metal exposure can potentially cause neurodevelopmental delays in children. This study examines whether prenatal exposure to mercury (Hg) and selenium (Se) is associated with the risk of neurodevelopmental delays in children up to 4 years of age. Children enrolled in a prospective birth cohort of the Japan Environment and Children's Study were examined. Hg and Se levels in maternal (nchild = 48,731) and cord (nchild = 3,083) blood were analyzed by inductively coupled plasma-mass spectrometry. Neurodevelopmental delays were assessed in children between the ages of 0.5 to 4 years using the Ages and Stages Questionnaires, Third Edition. The association between exposure and outcomes was examined using the generalized estimation equation models. In maternal blood, compared to participants with Se levels in the first quartile (83.0 to < 156 ng/g), the odds ratio (95 % confidence intervals) for problem-solving ability in children of mothers in the third (168 to < 181 ng/g) and fourth quartiles (181 to 976 ng/g) were 1.08 (1.01 to 1.14) and 1.10 (1.04 to 1.17), respectively. Furthermore, communication, gross and fine motor skills, and problem-solving delays were also observed. However, prenatal Hg levels in maternal and cord blood and Se levels in the latter were not associated with neurodevelopmental delays in children. Thus, the findings of this study suggest an association between Se levels in maternal blood and slightly increased risks of neurodevelopmental delays in children up to the age of 4 years.