Natural history, dynamics, and ecology of human papillomaviruses in genital infections of young women: protocol of the PAPCLEAR cohort study
Authors: Murall Carmen Lía , Rahmoun Massilva , Selinger Christian , Baldellou Monique , Bernat Claire , Bonneau Marine , Boué Vanina , Buisson Mathilde , Christophe Guillaume , D’Auria Giuseppe , Taroni Florence De , Foulongne Vincent , Froissart Rémy , Graf Christelle , Grasset Sophie , Groc Soraya , Hirtz Christophe , Jaussent Audrey , Lajoie Julie , Lorcy Frédérique , Picot Eric , Picot Marie-Christine , Ravel Jacques , Reynes Jacques , Rousset Thérèse , Seddiki Aziza , Teirlinck Martine , Tribout Vincent , Tuaillon Édouard , Waterboer Tim , Jacobs Nathalie , Bravo Ignacio G , Segondy Michel , Boulle Nathalie , Alizon Samuel 
Published: June 2019

IntroductionHuman 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 analysisThe 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 disseminationThis study has been approved by the Comité de Protection des Personnes Sud Méditerranée I (reference number 2016-A00712-49); by the Comité Consultatif sur le Traitement de l’Information en matière de Recherche dans le domaine de la Santé (reference number 16.504); by the Commission Nationale Informatique et Libertés (reference number MMS/ABD/AR1612278, decision number DR-2016–488) and by the Agence Nationale de Sécurité du Médicament et des Produits de Santé (reference 20160072000007). Results will be published in preprint servers, peer-reviewed journals and disseminated through conferences.Trial registration numberNCT02946346; Pre-results.