Natural history, dynamics, and ecology of human papillomaviruses in genital infections of young women: protocol of the PAPCLEAR cohort study

Introduction Human papillomaviruses (HPVs) are responsible for one-third of all cancers caused by infections. Most HPV studies focus on chronic infections and cancers, and we know little about the early stages of the infection. Our main objective is to better understand the course and natural history of cervical HPV infections in healthy, unvaccinated and vaccinated, young women, by characterising the dynamics of various infection-related populations (virus, epithelial cells, vaginal microbiota and immune effectors). Another objective is to analyse HPV diversity within hosts, and in the study population, in relation to co-factors (lifestyle characteristics, vaccination status, vaginal microbiota, human genetics). Methods and analysis The PAPCLEAR study is a single center longitudinal study following 150 women, aged 18–25 years, for up to 2 years. Visits occur every 2 or 4 months (depending on HPV status) during which several variables are measured, such as behaviours (via questionnaires), vaginal pH, HPV presence and viral load (via qPCR), local concentrations of cytokines (via MesoScale Discovery technology) and immune cells (via flow cytometry). Additional analyses are outsourced, such as titration of circulating anti-HPV antibodies, vaginal microbiota sequencing (16S and ITS1 loci) and human genotyping. To increase the statistical power of the epidemiological arm of the study, an additional 150 women are screened cross-sectionally. Finally, to maximise the resolution of the time series, participants are asked to perform weekly self-samples at home. Statistical analyses will involve classical tools in epidemiology, genomics and virus kinetics, and will be performed or coordinated by the Centre National de la Recherche Scientifique (CNRS) in Montpellier. Ethics and dissemination This study has been approved by the Comite de Protection des Personnes Sud Mediterranee I (reference number 2016-A00712-49); by the Comite Consultatif sur le Traitement de l’Information en matiere de Recherche dans le domaine de la Sante (reference number 16.504); by the Commission Nationale Informatique et Libertes (reference number MMS/ABD/AR1612278, decision number DR-2016–488) and by the Agence Nationale de Securite du Medicament et des Produits de Sante (reference 20160072000007). Results will be published in preprint servers, peer-reviewed journals and disseminated through conferences. Trial registration number NCT02946346; Pre-results.