The efficacy of human papillomavirus vaccination in young Japanese girls: the interim results of the OCEAN study.

Human papillomavirus (HPV) vaccine has been used to prevent chronic HPV infection, which accounts for cervical cancer. Japanese Ministry of Health, Labor and Welfare (MHLW) conducted an HPV vaccination campaign in 2010 and the Obstetrical Gynecological Society of Osaka initiated a multicenter, prospective cohort study in Osaka, Japan - OCEAN (Osaka Clinical resEArch of HPV vacciNe) study - to investigate the oncogenic HPV prevalence and the long-term protection rate of HPV vaccine. A total of 2814 participants were enrolled on their visit for HPV vaccination between 12 and 18 years old. Among them, 102 participants received HPV/Pap co-test as primary cancer screening at the age of 20-21. We compared the prevalence in two groups (the vaccinated and the unvaccinated group). HPV infection ratio was significantly lower in the vaccinated group compared to the unvaccinated (12.9% vs. 19.7%; p = .04). In particular, HPV 16 and 18 were not detected in the vaccinated group, while 4.9% of participants in the unvaccinated group were infected (p = .001), suggesting that vaccination provided effective protection against high-risk types of HPV. The cross-protection effect of HPV vaccines was also observed against HPV 31, 45, and 52. Although HPV vaccines were not contributed to the reduction of cervical intraepithelial neoplasia 1 (CIN) (p = .28), CIN2 or worse was not observed in vaccinated group. Our research showed that at the age of 20-21, HPV vaccine inhibited the infection of high-risk HPV and had impacted on the development to CIN2 or worse in Japan.

A survey of 20-year-old Japanese women: how is their intention to undergo cervical cancer screening associated with their childhood HPV vaccination status?

INTRODUCTION: In Japan, two groups of women, HPV vaccinated and unvaccinated, are approaching age 20, when they should begin cervical cancer screening. To improve Japan's current poor cervical cancer screening rate, we need to know how these women are thinking about screening. METHODS: We conducted an internet survey of 20-y-old women, exploring their understanding of HPV and cervical cancer screening. We then gave them leaflets with basic information about HPV and cervical cancer, stressing the importance of early detection by screening. We analyzed the leaflet's effects on their attitudes based on their vaccination status. RESULTS: Our study of 618 women found a significantly higher intention for engagement for cervical cancer screening in women HPV-vaccinated as teenagers (29% versus 17%). They were also more aware that: (1) HPV is transmitted by sexual intercourse (49.1% versus 39.2%); (2) the HPV vaccine prevents cervical cancer (49.0% to 34.0%); and (3) the appropriate cervical cancer screening interval is every 2 y (63.3% versus 56.2%). Women in both groups responded well to the leaflet, with significant improvements in intention to receive screening. However, 65%-67% were not swayed. DISCUSSION: HPV-vaccinated women were more knowledgeable about cervical cancer and had a greater intention to receive screening. Our educational leaflet was moderately effective in both groups for increasing intentions to screen, but the majority in both groups were still resistant to screening. CONCLUSION: Japan needs to develop more effective educational programs and tools to vigorously impart the importance of cervical cancer screening.

A survey of Japanese mothers on the effectiveness of the Ministry of Health, Labor and Welfare's revised HPV vaccine leaflet.

Introduction: In June of 2013, Japan's Ministry of Health, Labor and Welfare (MHLW) suspended its position of strong recommendation for the routine immunization of young girls against the Human Papilloma Virus (HPV) because of reports of adverse reactions after the vaccination. For the next four years, the MHLW's website warned about the significance of these adverse events. In January of 2018, MHLW's website was modified to reflect a less negative stance. We have studied public awareness of MHLW's revised leaflet in Japanese women whose daughters were of the targeted age for receiving the HPV vaccine and how this awareness influenced their intentions to get their daughters vaccinated. Materials and Methods: From June to December of 2018, a survey was conducted through the Departments of Obstetrics and Gynecology at 14 different medical facilities. The questionnaire was distributed to women whose daughters were of the HPV-vaccine-targeted age. The survey measured their responses before and after being presented with the 2018-revised MHLW leaflet. Responses from 384 mothers were analyzed. Results: Before being presented with the leaflet, the survey found that the percentage of responder's daughters already vaccinated was 6.5% (24/372). After reading the MHLW leaflet, an additional 6.9% (24/346) responded "I want to get my daughter vaccinated immediately", and 37.6% (130/346) responded "I have positive feelings about HPV vaccination". Discussion: By presenting the new MHLW leaflet at obstetrics and gynecology facilities, we expect to be able to effectively increase the HPV vaccination rate in Japan.

Safety of influenza vaccination on adverse birth outcomes among pregnant women: A prospective cohort study in Japan.

BACKGROUND: Pregnant women are in the highest priority group for receiving influenza vaccination. However, they may be reluctant to receive the vaccination due to concerns about the influence of vaccination on the fetuses. METHODS: This prospective cohort study of 10 330 pregnant women examined the safety of influenza vaccination in terms of adverse birth outcomes. Influenza vaccination during pregnancy was determined from questionnaires before and after the 2013/2014 influenza season. All subjects were followed until the end of their pregnancy. Adverse birth outcomes, including miscarriage, stillbirth, preterm birth, low birth weight, and malformation, were assessed by obstetrician reports. RESULTS: Adverse birth outcomes were reported for 641 (10%) of the 6387 unvaccinated pregnant women and 356 (9%) of the 3943 vaccinated pregnant women. Even after adjusting for potential confounders, vaccination during pregnancy showed no association with the risk of adverse birth outcomes (odds ratio 0.90, 95% confidence interval 0.76-1.07). Vaccination during the first or second trimester displayed no association with adverse birth outcomes, whereas vaccination during the third trimester was associated with a decreased risk of adverse birth outcomes (odds ratio 0.70, 95% confidence interval 0.51-0.98). CONCLUSIONS: Influenza vaccination during pregnancy did not increase the risk of adverse birth outcomes, regardless of the trimester in which vaccination was performed, when compared to unvaccinated pregnant women.

Time-dependent changes of the intention of mothers in Japan to inoculate their daughters with the HPV vaccine after suspension of governmental recommendation.

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.

Motivating Mothers to Recommend Their 20-Year-Old Daughters Receive Cervical Cancer Screening: A Randomized Study.

BACKGROUND: In Japan, the rate of cervical cancer screening is remarkably low, especially among women in their twenties and thirties, when cervical cancer is now increasing dramatically. The aim of this study was to test whether a modified government reminder for 20-year-old women to engage in cervical cancer screening, acting through maternal education and by asking for a maternal recommendation to the daughter to receive the screening, could increase their participation rate. METHODS: In two Japanese cities, 20-year-old girls who had not received their first cervical cancer screening before October of fiscal year 2014 were randomized into two study arms. One group of 1,274 received only a personalized daughter-directed reminder leaflet for cervical cancer screening. In the second group of 1,274, the daughters and their mothers received a combination package containing the same reminder leaflet as did the first group, plus an additional informational leaflet for the mother, which requested that the mother recommend that her daughter undergo cervical cancer screening. The subsequent post-reminder screening rates of these two study arms were compared. RESULTS: The cervical cancer screening rate of 20-year-old women whose mothers received the information leaflet was significantly higher than that for women who received only a leaflet for themselves (11% vs 9%, P = 0.0049). CONCLUSIONS: An intervention with mothers, by sending them a cervical cancer information leaflet with a request that they recommend that their daughter receive cervical cancer screening, significantly improved their daughters' screening rate.

Protective Effect of Maternal Influenza Vaccination on Influenza in Their Infants: A Prospective Cohort Study.

Background: Infants <6 months of age are too young to receive influenza vaccine, despite being at high risk for severe influenza-related complications. Methods: To examine the effectiveness of maternal influenza vaccination in preventing influenza in their infants, we conducted a prospective cohort study of 3441 infants born at participating hospitals before the 2013-2014 influenza season. At the time of recruitment, their mothers completed a questionnaire about influenza vaccination status for the 2013-2014 season. A follow-up survey was conducted after the end of the 2013-2014 season to collect information regarding influenza diagnosis and hospitalization among infants. Results: During the 2013-2014 influenza season, 71 infants (2%) had influenza diagnosed, and 13 infants (0.4%) were hospitalized with influenza. Maternal influenza vaccination (especially prenatal vaccination) decreased the odds of influenza among infants. The effectiveness of prenatal vaccination was 61% (95% confidence interval, 16%-81%), whereas that of postpartum vaccination was 53% (-28%-83%). Although maternal influenza vaccination was also associated with a decreased odds of influenza-related hospitalization among infants, vaccine effectiveness (73%) did not reach statistical significance, owing to the limited number of infants hospitalized because of influenza. Conclusions: The present findings indicated that pregnant women and postpartum women should receive influenza vaccination to protect their infants.

Estimating influenza disease burden among pregnant women: Application of self-control method.

To evaluate influenza disease burden among pregnant women, an epidemiological study using the self-control method was conducted. Study subjects were 12,838 pregnant women who visited collaborating maternity hospitals and clinics in Osaka Prefecture, Japan, before the 2013/14 influenza season. As a study outcome, hospitalization due to respiratory illnesses between the 2010/11 and 2013/14 seasons was collected from each study subject through a baseline survey at the time of recruitment and a second survey after the 2013/14 season. The hospitalization rates during pregnancy and non-pregnancy periods was calculated separately. To compare the hospitalization rate during pregnancy with that during non-pregnancy within the same single study subject, Mantel-Haenzel rate ratios (RRMH) were calculated. During the four seasons examined in this study, nine and 17 subjects were hospitalized due to respiratory illnesses during pregnancy and non-pregnancy periods, respectively. The hospitalization rate was 2.54 per 10,000 woman-months during pregnancy and 1.08 per 10,000 woman-months during non-pregnancy. The RRMH for the hospitalization rate during pregnancy compared with that during non-pregnancy was 4.30 (95% confidence interval, 1.96-9.41). Our results suggest that during the influenza season, pregnant women have a higher risk than non-pregnant women for hospitalization due to respiratory illnesses. The self-control method appears to be an appropriate epidemiological method for evaluating the disease burden of influenza among pregnant women.

Realistic fear of cervical cancer risk in Japan depending on birth year.

OBJECTIVE: In Japan, the possible adverse events upon HPV vaccination was widely reported in the media. MHLW announced the suspension of aggressively encouraging HPV vaccination in 2013, and inoculation rate has sharply declined. The aim of the present study was estimation of future cervical cancer risk. METHODS: The latest data on vaccination rate at each age in Sakai City were first investigated. The rate of experiencing sexual intercourse at the age of 12, 13, 14, 15, 16, 17 and throughout lifetime is assumed to be 0%, 1%, 2%, 5%, 15%, 25%, and 85% respectively. The cervical cancer risk was regarded to be proportional to the relative risk of HPV infection over the lifetime. The risk in those born in 1993 whom HPV vaccination was not available yet for was defined to be 1.0000. RESULTS: The cumulative vaccination rates were 65.8% in those born in 1994, 72.7% in 1995, 72.8% in 1996, 75.7% in 1997, 75.0% in 1998, 66.8% in 1999, 4.1% in 2000, 1.5% in 2001, 0.1% in 2002, and 0.1% in 2003. The relative cervical cancer risk in those born in 1994-1999 was reduced to 0.56-0.70, however, the rate in those born in 2000-2003 was 0.98-1.0, almost the same risk as before introduction of the vaccine. DISCUSSION: The cumulative initial vaccination rates were different by the year of birth. It is confirmed that the risk of future cervical cancer differs in accordance with the year of birth. For these females, cervical cancer screening should be recommended more strongly.

Development of an efficient strategy to improve HPV immunization coverage in Japan.

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 followed by the spread of vaccinations outward through these girls' circle of friends and acquaintances, and, finally, to the daughters of the most skeptical mothers, those who would await the return of new vaccine safety results from a large group of similarly-aged girls. As a critical step in improving HPV vaccine coverage in Japan, an educational information sheet that integrates the concepts of behavioral economics for changing behaviors can be employed to persuade mothers with poor decision-making facilities.

Project conducted in Hirakata to improve cervical cancer screening rates in 20-year-old Japanese: Influencing parents to recommend that their daughters undergo cervical cancer screening.

AIM: In Japan, the rate of routine cervical cancer screening is quite low, and the incidence of cervical cancer has recently been increasing. Our objective was to investigate ways to effectively influence parental willingness to recommend that their 20-year-old daughters undergo cervical cancer screening. METHODS: We targeted parents whose 20-year-old daughters were living with them. In fiscal year 2013, as usual, the daughter received a reminder postcard several months after they had received a free coupon for cervical cancer screening. In fiscal year 2014, the targeted parents received a cervical cancer information leaflet, as well as a cartoon about cervical cancer to show to their daughters, with a request that they recommend to their daughter that she undergo cervical cancer screening. The subsequent screening rates for fiscal years 2013 and 2014 were compared. RESULTS: The cervical cancer screening rate of 20-year-old women whose parents received the information packet in fiscal year 2014 was significantly higher than for the women who, in fiscal year 2013, received only a simple reminder postcard (P < 0.001). As a result, the total screening rate for 20-year-old women for the whole of the 2014 fiscal year was significantly increased over 2013 (P < 0.001). CONCLUSION: For the first time, we have shown that the parents of 20-year-old daughters can be motivated to recommend that their daughters receive their first cervical cancer screening. This was achieved by sending a cervical cancer information leaflet and a cartoon about cervical cancer for these parents to show to their daughters. This method was significantly effective for improving cervical cancer screening rates.

Mothers' attitudes in Japan regarding cervical cancer screening correlates with intention to recommend cervical cancer screening for daughters.

BACKGROUND: Cervical cancer and its precancerous lesions caused by human papilloma virus (HPV) are steadily increasing in women in Japan. In comparison with women in other resource-rich countries, young women in Japan have a dismally low screening rate for cervical cancer. Our preliminary research has shown that 20-year-old women in Japan usually ask their mothers for advice regarding their initial cervical cancer screening. The objective of our current research is to determine the social factors among mothers in Japan that are causing them to give advice to their daughters regarding the HPV vaccine and cervical cancer screening. METHODS: The survey's targets were mothers who had 20-year-old daughters. We recruited respondents from the roster of a commercial internet survey panel. We analyzed for correlations between a mother's knowledge concerning cervical cancer, her recent cancer screening history, and the advice she gave to her daughter regarding cervical cancer screening. RESULTS: We obtained 618 valid answers to the survey. Compared with mothers who did not get screening, mothers who had cervical cancer screening had significantly more knowledge about cervical cancer and its screening (p < 0.05). The daughters of mothers with recent screening had received HPV vaccination more often than those of mothers without recent screening (p = 0.018). Mothers with recent screening histories tended more often to encourage their daughters to have cervical cancer screening (p < 0.05). When mothers were properly educated concerning cervical cancer and its screening, they were significantly more likely than before to recommend that their daughters have it (p < 0.0001). CONCLUSIONS: In young Japanese women, given the important role their mothers have in their lives, it is probable that we could improve their cervical cancer screening rate significantly by giving their mothers better medical information, and a chance to experience cervical cancer screening for themselves.

Survey of Japanese mothers of daughters eligible for human papillomavirus vaccination on attitudes about media reports of adverse events and the suspension of governmental recommendation for vaccination.

AIM: Following media reports of adverse medical events surrounding human papillomavirus (HPV) vaccination and the suspension of Japanese governmental recommendation, most adolescents have refrained from receiving the vaccine. This represents a national critical event, because the incidence of cervical cancer in Japan continues to increase. METHODS: We conducted an Internet survey to investigate why Japanese adolescent girls decline, continue or discontinue their HPV vaccination, how their mothers influence their decision, and the mothers' feelings about future HPV vaccination for their daughters. One thousand mothers with daughters 10-18 years of age were recruited for our questionnaire. RESULTS: Our results suggest that acceptance of the HPV vaccine was determined predominantly by the mother's perceptions of risk versus benefits, rather than the daughter's wishes. The mothers' knowledge of the benefits of the prophylactic HPV vaccine and their attitude toward cervical cancer screening influenced their decision whether to allow their daughter to receive future vaccinations. The tenor of survey responses of those mothers who were anti-vaccine changed significantly to the positive in response to a proposed scenario where the governmental recommendation for the HPV vaccine was reinstated, whereas a hypothetical educational intervention sheet did not significantly change their attitude. CONCLUSIONS: Promotion of the HPV vaccine through comprehensive education for both mothers and daughters, not only on the vaccine itself, but also about cervical cancer and screening, is required for any successful program to prevent cervical cancer.

Effect on HPV vaccination in Japan resulting from news report of adverse events and suspension of governmental recommendation for HPV vaccination.

BACKGROUND: Administration of the human papillomavirus (HPV) vaccine decreased dramatically in Japan after extensive news of adverse vaccine events and suspension of the governmental recommendation for the vaccine. In this study, we investigated the knowledge and acceptance of vaccinated adolescents concerning cervical cancer, cancer screening and the HPV vaccine. Furthermore, we analyzed whether and by how much the news affected acceptance of the vaccination. METHODS: This study was conducted as a part of Osaka Clinical resEArch of HPV vacciNe (OCEAN) study. A questionnaire was distributed to 2,777 study registrants. RESULTS: The response rate was 38%. The recognition rate of the news of the vaccine's adverse events was 80%; it was 68% for awareness of the government's announcement of the suspension of its recommendation for the vaccine. Among those who had a chance to hear or see the negative news during their vaccination period, 46 (60%) continued vaccination while knowing of the news, 22 (29%) discontinued vaccination, and 9 (11%) continued vaccination without an awareness of the news. Reports of the vaccine's adverse events were the main reason for not continuing the vaccination series. Those who consulted doctors after hearing the adverse news were significantly more likely to continue their vaccinations than those who did not. CONCLUSIONS: Our results should help in understanding the need for a strong promotion of vaccine usage and cancer screening after future retraction of the recommendation suspension. This may apply to other countries with an unsatisfactory rate of HPV vaccination due to fears of adverse vaccine events.

Long-term hospitalization during pregnancy is a risk factor for vitamin D deficiency in neonates.

In order to examine the effects of long-term hospitalization during pregnancy on vitamin D metabolism in pregnant women and neonates, we measured the serum 25-hydroxyvitamin D (25OHD) levels in pregnant women, as well as measuring 25OHD levels in cord blood and breast milk. In pregnant women hospitalized for longer than 1 month, the serum 25OHD levels were decreased at delivery compared with those in control subjects (10.9 +/- 2.6 ng/l vs 19.5 +/- 4.9 ng/l; P < 0.01). Although the levels of 25OHD in the cord blood were not significantly different between the long-term hospitalized and control pregnant women in this study (9.36 +/- 1.7 ng/l vs 11.1 +/- 3.0 ng/l), the 25OHD concentrations in the cord blood were significantly lower than the maternal levels in both groups; the ratios of the levels in cord blood to sera in the long-term hospitalized women and control subjects were 82.1% and 60.3%, respectively. Long maternal hospitalization does not always cause neonatal vitamin D deficiency, but could be one of its major risk factors. Therefore, sufficient sunlight exposure and intake of sufficient vitamin D are considered to be important to prevent vitamin D deficiency in long-term hospitalized pregnant women as well as their babies.