Human Papillomavirus Vaccination by Birth Fiscal Year in Japan

Yagi A., Ueda Y., Oka E., et al. Human Papillomavirus Vaccination by Birth Fiscal Year in Japan. JAMA network open 7, e2422513 (2024); https://doi.org/10.1001/jamanetworkopen.2024.22513.Importance: The Ministry of Health, Labour, and Welfare (MHLW) of Japan aggregates human papillomavirus (HPV) vaccination data across Japan for each fiscal year (FY) by age at vaccination. Birth FY (BFY)-specific vaccination coverage remains unknown. Objective: To calculate the BFY-specific vaccination coverage for each FY and the cumulative first-dose coverage for each BFY in Japan, to understand the generation-specific vaccination coverage, and to estimate the cumulative first-dose coverage of each BFY that would be achieved by FY 2028 vs World Health Organization (WHO) targets. Design, Setting, and Participants: In this cross-sectional study, MHLW-published national age-specific HPV vaccination numbers and demographic data for female individuals were used to calculate the BFY-specific first-dose coverage for each FY and the BFY-specific cumulative first-dose coverage. It was assumed that the BFYs 2007 to 2012 vaccination coverage in FY 2023 to 2028 would remain the same as the vaccination coverage of the same grade in FY 2022 to estimate the cumulative first-dose coverage that would be achieved by FY 2028. Data analysis was performed from December 2023 to January 2024. Exposure: Two MHLW policy changes were the government's suspension of proactive recommendation for HPV vaccination in June 2013 and the government's resumption of proactive recommendation for HPV vaccination in April 2022. Main Outcomes and Measures: The primary outcome was generation-specific vaccination coverage among female individuals born in BFYs 1994 to 2010 in FYs 2010 to 2022, calculated using reconfigured published data. Results: In this study of vaccination data for 9 414 620 female individuals, the generation-specific vaccination coverage was 71.96% for the vaccination generation (BFYs 1994-1999), 4.62% for the vaccine-suspension generation (BFYs 2000-2003), 16.16% for the generation that received information individually (BFYs 2004-2009), and 2.83% for the vaccine-resumed generation (BFY 2010). HPV routine vaccination coverage was extremely low in BFYs 2000 to 2010 (0.84%-25.21%) vs BFYs 1994 to 1999 (53.31%-79.47%). The cumulative first-dose coverage that was estimated to be achieved in the vaccine-resumed generation by FY 2028 plateaued at 43.16%. Conclusions and Relevance: Even after the resumption of MHLW's proactive recommendations, HPV vaccination coverage has only minimally recovered in Japan. The cumulative first-dose coverage that was estimated to be achieved in the vaccine-resumed generation by FY 2028 is below the WHO target. These findings reveal that stronger cervical cancer control measures are required, particularly for the vaccine-resumed generation, which will plateau at approximately one-half the WHO target values

Even though active recommendation for HPV vaccination has restarted, Japan's rates have not recovered

Yagi A., Ueda Y., Oka E., et al. Even though active recommendation for HPV vaccination has restarted, Japan's rates have not recovered. Cancer Science , (2024); https://doi.org/10.1111/cas.16167.Japan has a particularly critical situation surrounding its collapsed HPV vaccination program for preventing HPV-caused cervical cancers, a problem exacerbated by the lack of a national immunization database. We have determined the year-to-year HPV vaccination uptake by Japanese females and analyzed by birth fiscal year (FY) the monthly number of people receiving initial HPV vaccination. Our analysis covers the period from the start of public subsidies in 2010 to September 2023, using data provided by local governments. We calculated the cumulative number of monthly immunizations for those unimmunized as of April (the beginning of each vaccination year). The monthly number of initial HPV vaccinations was highest in August for every FY from FY 2010 to FY 2023; a second vaccination peak tended to occur in March when the vaccination year ended. The highest number of August vaccinations occurred in FY 2011, followed (in order) by 2012, 2021, 2022, 2023, and 2013. In Japan's ongoing catch-up vaccination program for young women, the monthly number of vaccinations increased in August 2022 but then slowed the following year. After FY 2021, the cumulative vaccination coverage of subjects unvaccinated at the beginning of the vaccination year but subsequently covered by routine immunizations was slightly improved. FY 2021 was when the governmental recommendations for HPV vaccination were resumed. More recent vaccination rates are considerably lower than those in FY 2011–2012 when vaccinations were first fully endorsed. Paralyzing HPV vaccination hesitancy, which began in FY 2013, will linger in Japan in FY 2024

Virtual screening identifies a novel piperazine-based insect juvenile hormone agonist

Juvenile hormone (JH) agonists constitute a subclass of insect growth regulators and play important roles in insect pest management. In this work, a multi-step virtual screening program was executed to find novel JH agonists. A database of 5 million purchasable compounds was sequentially processed with three computational filters: (i) shape and chemical similarity as compared to known JH-active compounds; (ii) molecular docking simulations against a Drosophila JH receptor, methoprene-tolerant; and (iii) free energy calculation of ligand–receptor binding using a modified MM/PBSA (molecular mechanics/Poisson–Boltzmann surface area) protocol. The 11 candidates that passed the three filters were evaluated in a luciferase reporter assay, leading to the identification of a hit compound that contains a piperazine ring system (EC₅₀=870 nM). This compound is structurally dissimilar to known JH agonists and synthetically easy to access; therefore, it is a promising starting point for further structure optimization

Macrophage HIF-1α increases liver tumor

Aims/Introduction: Chronic inflammation of the liver is often observed with obesity or type 2 diabetes. In these pathological conditions, the immunological cells, such as macrophages, play important roles in the development or growth of liver cancer. Recently, it was reported that hypoxia‐inducible factor‐1α (HIF‐1α) is a key molecule for the acquisition of inflammatory M1 polarity of macrophages. In the present study, we examined the effects of altered macrophage polarity on obesity‐ and diabetes‐associated liver cancer using macrophage‐specific HIF‐1α knockout (KO) mice. Materials and Methods: To induce liver cancer in the mice, diethylnitrosamine, a chemical carcinogen, was used. Both KO mice and wild‐type littermates were fed either a high‐fat diet (HFD) or normal chow. They were mainly analyzed 6 months after HFD feeding. Results: Development of liver cancer after HFD feeding was 45% less in KO mice than in wild‐type littermates mice. Phosphorylation of extracellular signal‐regulated kinase 2 was also lower in the liver of KO mice. Those effects of HIF‐1α deletion in macrophages were not observed in normal chow‐fed mice. Furthermore, the size of liver tumors did not differ between KO and wild‐type littermates mice, even those on a HFD. These results suggest that the activation of macrophage HIF‐1α by HFD is involved not in the growth, but in the development of liver cancer with the enhanced oncogenic extracellular signal‐regulated kinase 2 signaling in hepatocytes. Conclusions: The activation of macrophage HIF‐1α might play important roles in the development of liver cancer associated with diet‐induced obesity and diabetes

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

Yagi A., Nakagawa S., Ueda Y., et al. Effectiveness of catch-up and routine program of the 9-valent vaccine on cervical cancer risk reduction in Japan. Cancer Science 115, 916 (2024); https://doi.org/10.1111/cas.16055.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

Contribution of visceral adiposity and insulin resistance to metabolic risk factors in Japanese men

金沢大学大学院医学系研究科北陸中央病院内科We investigated the relative impacts of visceral adiposity and insulin resistance on the metabolic risk profile in middle-aged Japanese men. A cross-sectional study was conducted in 636 nondiabetic Japanese men with a mean age of 51.6 years. Visceral adipose tissue (AT) was assessed using computed tomography, and insulin resistance was determined by the homeostasis model assessment of insulin resistance (HOMA-IR). Metabolic risk factors were diagnosed according to the National Cholesterol Education Program Adult Treatment Panel III metabolic syndrome criteria: (1) hypertriglyceridemia, (2) low high-density lipoprotein cholesterol, (3) hypertension, (4) impaired fasting glucose, and (5) impaired glucose tolerance. Visceral AT and HOMA-IR were significantly and positively correlated with each other (r = 0.41, P < .001). Using the 75th percentile value as a cut point, those with isolated large visceral AT showed significantly greater odds ratios for each of the 5 risk factors measured except impaired fasting glucose, whereas those with isolated high HOMA-IR showed significantly greater odds ratios for each of the 5 risk factors except hypertriglyceridemia and impaired glucose tolerance, compared with the control group. The combined group (increased visceral AT and HOMA-IR) had the highest odds ratios for all studied risk factors. On logistic regression analysis using visceral AT and HOMA-IR as continuous independent variables, they were each independently associated with most of the metabolic risk factors and their clustering. In conclusion, neither visceral AT nor HOMA-IR stands out as the sole driving force of the risk profile; each makes a significant contribution to metabolic abnormalities in Japanese men. © 2010 Elsevier Inc. All rights reserved

Paraspeckles are subpopulation-specific nuclear bodies that are not essential in mice

Mouse NEAT1 is required for paraspeckle formation in a subset of cells but is not essential for animal health and viability

スイ カイメンジョウ リンパカンシュ cavernous lymphangioma of the pancreas ニ タイシテ フククウキョウカ シュヨウ テキシュツジュツ オ オコナッタ 1レイ

Cavernous lymphangioma of the pancreas is a rare condition, recognized as nonepithelial pancreatic cystic tumors. This is the first case report, to our knowledge, of performance of a laparoscopic excision for lymphangioma of the pancreas. A 49 year-old male presented with an enlarged cystic tumor involving the pancreas body and tail and without abdominal pain, was prepared for laparoscopic excision. The surgical specimen showed a multicystic mass measuring 7.0×5.5×3.0cm, which was diagnosed as a benign lymphangioma with cavernous features. The patient remains symptom free 4 years after laparoscopic excisio