Viral and immune dynamics of HPV genital infections in young women

Human papillomavirus (HPV) infections drive one in twenty new cancer cases. Despite the potential for improving treatment, screening, and vaccination strategies, little is known as to why most HPV infections clear spontaneously within two years. To untangle the dynamics of these non-persisting infections, we performed a combined quantitative analysis of virological, immunological, and clinical data from an original longitudinal cohort of 189 women with high temporal resolution. We find that HPV viral load reaches a plateau within two months, and clears within a median time of 14 months. Furthermore, we identify immune correlates associated with infection clearance, especially TCR-gamma-delta cells. Our results open new perspectives for understanding the frontier between acute and chronic infections and for controlling HPVassociated diseases. ### Competing Interest Statement T.W. serves on advisory boards for MSD (Merck Sharp and Dohme). J. R. reports personal fees from Gilead (consulting and payment or honoraria for lectures, presentations, speaker's bureaus, manuscript writing, or educational events), Janssen (payment or honoraria for lectures, presentations, speaker's bureaus, manuscript writing, or educational events), Merck (payment or honoraria for lectures, presentations, speaker's bureaus, manuscript writing, or educational events), Theratechnologies (payment or honoraria for lectures, presentations, speaker's bureaus, manuscript writing, or educational events), and ViiV Healthcare (consulting and payment or honoraria for lectures, presentations, speaker's bureaus, manuscript writing, or educational events) and support for attending meetings and/or travel from Gilead and Pfizer, outside of the submitted work. All the other authors do not report any conflict of interest. ### Funding Statement This project has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement No 648963, to SA). The authors acknowledge further support from the Centre National de la Recherche Scientifique, the Institut de Recherche pour le Développement, the Fédération Hospitalière Universitaire InCH of Montpellier, the Fondation pour la Recherche Médicale (to TK), the Ligue contre le Cancer (to TB), and the Agence Nationale de la Recherche contre le Sida (ANRS-MIE, to NT and OS). The authors acknowledge the ISO 9001 certified IRD i-Trop HPC (member of the South Green Platform) at IRD Montpellier for providing HPC resources that have contributed to the research results reported within this article (bioinfo.ird.fr and www.southgreen.fr) ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study has been approved by the Comité de Protection des Personnes (CPP) 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), by the Agence Nationale de Sécurité du Médicament et des Produits de Santé - (reference 20160072000007), and is registered at ClinicalTrials.gov under the ID [NCT02946346][1]. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The raw data and R scripts used will be deposited on the Zenodo server upon publication. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT02946346&atom=%2Fmedrxiv%2Fearly%2F2023%2F05%2F16%2F2023.05.11.23289843.atom