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Increased Age-Adjusted Cancer Mortality After the Third mRNA-Lipid Nanoparticle Vaccine Dose During the COVID-19 Pandemic in Japan

During the COVID-19 pandemic, excess deaths including cancer have become a concern in Japan, which has a rapidly aging population. Thus, this study aimed to evaluate how age-adjusted mortality rates (AMRs) for different types of cancer in Japan changed during the COVID-19 pandemic (2020-2022). Official statistics from Japan were used to compare observed annual and monthly AMRs with predicted rates based on pre-pandemic (2010-2019) figures using logistic regression analysis. No significant excess mortality was observed during the first year of the pandemic (2020). However, some excess cancer mortalities were observed in 2021 after mass vaccination with the first and second vaccine doses, and significant excess mortalities were observed for all cancers and some specific types of cancer (including ovarian cancer, leukemia, prostate cancer, lip/oral/pharyngeal cancer, pancreatic cancer, and breast cancer) after mass vaccination with the third dose in 2022. AMRs for the four cancers with the most deaths (lung, colorectal, stomach, and liver) showed a decreasing trend until the first year of the pandemic in 2020, but the rate of decrease slowed in 2021 and 2022. This study discusses possible explanations for these increases in age-adjusted cancer mortality rates.


Introduction


The COVID-19 pandemic began in December 2019 in Wuhan, China, and was first detected in Japan in January 2020. In response, a range of healthcare and socio-economic restrictions were implemented to curb the spread of the disease. Since February 2021, the mRNA-lipid nanoparticle (mRNA-LNP) vaccine has been available for emergency use and is recommended for all individuals aged six months and older, especially those at high risk. As of March 2023, 80% of the Japanese population had received their first and second doses, 68% had received their third dose, and 45% had received their fourth dose [1]. Despite these national measures, 33.8 million people had been infected, and 74,500 deaths had been attributed to COVID-19 in Japan by the end of April 2023. Additionally, excess deaths from causes other than COVID-19 have been reported in various countries [2-6], including deaths from cancer [7-10], and Japan is no exception [11,12]. Cancer is the leading cause of death in Japan, accounting for one-fourth of all deaths. Therefore, it is essential to understand the effects of the pandemic on mortality rates of cancer from 2020 to 2022. Age adjustment is necessary for accurate evaluation, especially in diseases such as cancer that tend to occur in elderly adults. Japan has several characteristics that make it ideal for analyzing the impact of the pandemic on cancer mortality rates, including its large population of 123 million, availability of official statistics, and the high 80% accuracy rate of death certificates according to autopsy studies [13].



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