National genotype prevalence and age distribution of human papillomavirus from infection to cervical cancer in Japanese women: a systematic review and meta-analysis protocol

Background: Despite prophylactic human papillomavirus (HPV) vaccination being a safe, effective and cost-effective public health intervention for the prevention of cervical cancer, the HPV vaccine is not actively recommended or promoted by the Ministry of Health Labour and Welfare in Japan. With already very low levels of cervical screening below 30%, and vaccination levels that are below levels that award any population effect at 0.3% of the eligible population, cervical cancer mortality is higher than other similar high-income countries at 4.4/100,000 (2900) deaths per year in 2015. There is limited population-based or nationally representative data for HPV genotype distribution in Japan, thus making an assessment of the burden of vaccine-preventable cervical cancer difficult. Therefore, this systematic review and meta-analysis aims to determine the HPV genotype prevalence and age distribution of HPV infection in women with a cytological or histological diagnosis of normal through cervical cancer in Japan. We anticipate this information will guide and enhance programme interventions to reduce vaccine-preventable cervical cancer mortality in Japan. Methods: PubMed, Embase and the Japan Medical Abstract Society Database will be searched from the date of establishment to March 2021 to identify original research articles that report the prevalence of HPV genotypes in Japanese women with normal cervical cytology, low grade, high grade and cancerous cervical lesions. No exclusion criteria relating to language or publication date will be applied. The quality of the studies will be assessed using the Joanna Briggs checklist for prevalence studies. Randomised control trials, cohort studies, cross-sectional and prevalence studies will be considered eligible. Study findings will be combined using a traditional random-effects or fixed-effects meta-analysis to summarise pooled prevalence and 95% confidence intervals depending on heterogeneity. Subgroup analyses and meta-regression will be used to investigate heterogeneity, and sensitivity analyses will be conducted to assess the robustness of the findings. Discussion: To our knowledge, this is the first systematic review protocol that includes both Japanese and English peer-reviewed articles for the determination of genotype-specific HPV prevalence in cytological or histological confirmed normal cervical specimens, low- and high-grade intraepithelial lesions and cervical cancers by age in Japan. We anticipate this information will guide and enhance programme interventions to reduce vaccine-preventable cervical cancer mortality in Japan. Systematic review registration: PROSPERO CRD42018117596