Hiromi Murata

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

ABSTRACT 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.

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

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.

Decidualization of the human endometrium

Decidualization of the human endometrium, which involves a dramatic morphological and functional differentiation of human endometrial stromal cells (ESCs), is essential for the establishment of a successful pregnancy. Decidualization results from a complex interplay of transcription factors, morphogens, cytokines, cell cycle regulators, and signaling pathways.

The steroid hormone dydrogesterone inhibits myometrial contraction independently of the progesterone/progesterone receptor pathway

Aims: In this study, we aimed to investigate the direct effects of steroid hormones on pregnant myometrial contraction. Main methods: The effect of steroids on oxytocin‐induced contraction was examined in vitro using pregnant rat or human myometrium. Subsequently, we evaluated whether RU486, a potent progesterone antagonist, influenced the effects of progestin on myometrial contraction. Additionally, we evaluated the effects of progestin on high‐concentration KCl‐induced contraction caused by voltage‐dependent calcium channels in order to investigate the mechanisms involved in this process. Key findings: Of the natural steroids examined, 17&bgr;‐estradiol, progesterone, testosterone, cortisol, and aldosterone did not influence oxytocin‐induced contraction at concentrations <10−6M. Of the tested progestins, medroxyprogesterone acetate, norethisterone, chlormadinone acetate, levonorgesterol, 17&agr;‐hydroxyprogesterone capronate, and dienogest had no effect on contraction at <10−6M. However, dydrogesterone showed rapid and direct inhibition of contraction at 10−6M, and this inhibitory effect was dependent on dose and time. RU486 did not block the inhibitory effects of dydrogesterone on contraction. High‐concentration KCl‐induced contraction was also inhibited by dydrogesterone, and the inhibitory effects of dydrogesterone were observed at concentrations as low as 10−7M. Additionally, oxytocin‐induced contraction in pregnant human myometrium was inhibited by 10−6M dydrogesterone. Significance: These results suggested that the rapid and direct effects of dydrogesterone on myometrial contraction were caused by a nongenomic pathway and that the progesterone receptor was not required for dydrogesterone action. Additionally, the mechanism of dydrogesterone action may involve voltage‐dependent calcium channels.

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

ABSTRACT 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.

Regulation of Angiogenesis in the Human Endometrium

The physiological changes in the endometrium in response to hypoxia and female sex hormones are associated with profound angiogenesis. Hypoxia in the endometrial tissues is a major regulator of endometrial angiogenesis and remodeling during menstruation. Estradiol plays an important role in the reconstruction of a new vascular network and rapid vessel growth in the endometrium. Progesterone is a key factor in vascular maturation and decidualization. Further, endometrial angiogenesis is tightly controlled by a variety of angiogenic and antiangiogenic factors including vascular endothelial growth factor (VEGF), soluble VEGF receptor-1, angiopoietin, and CXCL12. Hypoxia and female sex hormones are involved in the regulation of the angiogenic factors in an independent manner in human endometrium. Analysis of the process of angiogenesis in the human endometrium will enhance our understanding of normal endometrial vascular remodeling.