Viral and immune dynamics of genital human papillomavirus infections in young women with high temporal resolution
Authors: Tessandier Nicolas , Elie Baptiste , Boué Vanina , Selinger Christian , Rahmoun Massilva , Bernat Claire , Grasset Sophie , Groc Soraya , Bedin Anne-Sophie , Beneteau Thomas , Bonneau Marine , Graf Christelle , Jacobs Nathalie , Kamiya Tsukushi , Kerioui Marion , Lajoie Julie , Melki Imène , Prétet Jean-Luc , Reyné Bastien , Schlecht-Louf Géraldine , Sofonea Mircea T. , Supplisson Olivier , Wymant Chris , Foulongne Vincent , Guedj Jérémie , Hirtz Christophe , Picot Marie-Christine , Reynes Jacques , Tribout Vincent , Tuaillon Édouard , Waterboer Tim , Segondy Michel , Bravo Ignacio G. , Boulle Nathalie , Murall Carmen Lía , Alizon Samuel 
Published: January 2025

Human papillomavirus (HPV) infections drive one in 20 new cancer cases, exerting a particularly high burden on women. Most anogenital HPV infections are cleared in less than two years, but the underlying mechanisms that favour persistence in around 10% of women remain largely unknown. Notwithstanding, it is precisely this information that is crucial for improving treatment, screening, and vaccination strategies. To understand viral and immune dynamics in non-persisting HPV infections, we set up an observational longitudinal cohort study with frequent on-site visits for biological sample collection. We enrolled 189 women aged from 18 to 25 and living in the area of Montpellier (France) between 2016 and 2020. We performed 974 on-site visits for a total of 1,619 months of follow-up. We collected data on virus load, local immune cell populations, local concentrations of cytokines, and circulating antibody titres. Using hierarchical Bayesian statistical modelling to simultaneously analyse the data from 164 HPV infections from 76 participants, we show that in two months after infection, HPV viral load in non-persisting infections reaches a plateau that lasts on average for 13 to 20 months (95% credibility interval) and is then followed by a rapid clearance phase. This first description of the dynamics of HPV infections comes with the identification of immune correlates associated with infection clearance, especially gamma-delta T cells and CXCL10 concentration. A limitation of this study on HPV kinetics is that many infection follow-ups are censored. Furthermore, some immune cell populations are difficult to label because cervical immunity is less well characterised than systemic immunity. These results open new perspectives for understanding the frontier between acute and chronic infections, and for controlling HPV-associated diseases, as well as for research on human cancers of infectious origin.

Trial Registration: This trial was registered is registered at ClinicalTrials.gov under the ID NCT02946346. 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).