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BMJ Open. 2019 Jun 11;9(6):e025129. doi: 10.1136/bmjopen-2018-025129.

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

Author information

MIVEGEC (UMR 5290 CNRS, IRD, UM), CNRS, Montpellier, France.
Center for Free Information, Screening and Diagnosis (CGIDD), Centre Hospitalier Universitaire de Montpellier, Montpellier, France.
Department of Obstetrics and Gynaecology, Centre Hospitalier Universitaire de Montpellier, Montpellier, France.
Department of Research and Innovation (DRI), Centre Hospitalier Universitaire de Montpellier, Montpellier, France.
CIBER en Epidemiología y Salud Pública (CIBEResp), Madrid, Spain.
Sequencing and Bioinformatics Service, Fundaciónpara el Fomento de la Investigación Sanitaria y Biomédica de laComunidad Valenciana (FISABIO-Salud Pública), Valencia, Spain.
Pathogenesis and Control of Chronic Infections, INSERM, CHU, University of Montpellier, Montpellier, France.
Department of Virology, Centre Hospitalier Universitaire de Montpellier, Montpellier, France.
LBPC/PPC- IRMB, CHU de Montpellier and Université de Montpellier, Montpellier, France.
Department of Medical Information (DIM), Centre Hospitalier Universitaire de Montpellier, Montpellier, France.
Department of Medical microbiology, University of Manitoba, Winnipeg, Manitoba, Canada.
Department of pathology and oncobiology, Centre Hospitalier Universitaire de Montpellier, Montpellier, France.
Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Department of Infectious and Tropical Diseases, Centre Hospitalier Universitaire de Montpellier, Montpellier, France.
German Cancer Research Center (DKFZ), Infections and Cancer Epidemiology, Heidelberg, Germany.
GIGA-Research, Cellular and molecular immunology, University of Liège, Liège, Belgium.



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).


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.


This 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.


NCT02946346; Pre-results.


HPV; acute infection; immunity; microbiota; persistence; viral kinetics; virus load

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