The association of HPV infection and vaginal microbiota of reproductive women in China: A multicenter cohort study protocol

Abstract Background: Cervical cancer is a global health concern. Persistent oncogenic human papillomavirus (HPV) infection is a prerequisite for the development of cervical cancer. Emerging research indicates that the vaginal microbiota may play both protective and harmful roles in the acquisition and persistence of HPV and the development of cervical intraepithelial neoplasia (CIN). So far, there is no large-scale longitudinal female vaginal microbiota (VM) study worldwide to reveal the association between vaginal microbiota and the outcome of HPV infection.Methods: This multicenter cohort study will recruit 50 research centers and enroll a total of about 10,000 female volunteers across the country. This study has developed a series of strict inclusion and exclusion criteria for the volunteers. Researchers will draw up a unified questionnaire generated by this protocol to obtain the sociodemographic information, clinical data and lifestyle of all volunteers. Specimens including vaginal secretions and cervical exfoliated cells will be collected at the first visit and follow-up after six months. All samples will be processed in the certified laboratory of the research centers. Twenty-one HPV genetypes and other sexually transmitted pathogens, including Neisseria gonorrhoeae, Chlamydia trachomatis, Ureaplasma urealyticum, Mycoplasma hominis, Mycoplasma genitalium and Herpes simplex virus type Ⅱ will be tested in the first visit and follow-up after six months. Strict quality control will be conducted among every research center, including training staffs and reviewing the qualifications of participating researchers responsible for acquiring data and processing samples.Discussion: The association of HPV infection and vaginal microbiota will be explored in the registry study. In addition, the core microbiota attributes to the persistent HPV infection will be analyzed. The present study aims to create a nationwide database of vaginal microbiota of women in reproductive age.Trial registration: This study has registered in ClinicalTrials.gov (ClinicalTrials.gov Identifier: NCT04694495). Registered: 5 January 2021 Retrospectively registered. https://clinicaltrials.gov/ct2/results?cond=&term=NCT04694495&cntry=&state=&city=&dist=