HPV detection patterns in young women from the PAPCLEAR longitudinal study: implications for HPV screening policies

Objectives HPV infections are ubiquitous. For most infections, we lose track of the presence of the virus in host in less than three years after the start of infection. The mechanisms regulating the persistence of HPV infection are still partially understood. In this work, we focus on incident HPV detection in young women and we characterise the dynamics of these infections and evaluate the effect of genotype and host socio-economic factors on the duration of HPV detection and time between detection. Methods We investigated human papillomavirus (HPV) genotype detection patterns in 182 young women in Montpellier, France. We relied on SPF10-LiPA25 screening assay for the simultaneous de-tection of 25 HPV genotypes. We used survival analysis tools with frailty effects to investigate the contribution of viral and host factors to variations in the time of HPV detectability, time of first incident detection, and time before re-detection. Results Women of the PAPCLEAR cohort experienced numerous positive HPV events, including frequent redetection of the same genotype. We retrieve classical results that HR-genotypes are detected for longer duration than LR-genotypes. HR-genotypes were also more liekly to be detected than LR-genotypes during the follow-up. The number of lifetime sexual partner was strongly associated with increased risk of new positive detection while vaccination was related to a lower risk of displaying incident infections. Covariates related to socio-economic difficulties were associated with longer duration of HPV positivity. Conclusions Young women display numerous event of HPV detection, with frequent codetections of multiple genotypes at the same time and redetection of the same type after periods of no detection. These new detection are almost certainly the result of new acquisition from sexual partners, with little evidence of re-emergence of latent infections. A better characterisation of transient infections might help unveil doubts and misconception on HPV physiopathology, favouring adherence to preventive policies. ### Competing Interest Statement 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 or personal relationships that could have appeared to influence the work reported in this paper. ### Funding Statement TB is funded by la Ligue contre le Cancer (grant No TAKX21133). This work was supported by the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement No 648963 to SA). The sponsor had no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication. ### 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: The PAPCLEAR trial was promoted by the Centre Hospitalier Universitaire de Montpellier and approved by the Comité de Protection des Personnes (CPP) Sud Méditerranée I on 11 May 2016 (CPP number 16 42, reference number ID RCB 2016A00712-49); by the Comité Consultatif sur le Traitement de l'Information en matière de Recherche dans le domaine de la Santé on 12 July 2016 (reference number 16.504); and by the Commission Nationale Informatique et Libertés on 16 December 2016 (reference number MMS/ABD/AR1612278, decision number DR-2016488). This trial was authorised by the Agence Nationale de Sécurité du Médicament et des Produits de Santé on 20 July 2016 (reference 20160072000007). The [ClinicalTrials.gov][1] identifier is [NCT02946346][2]. All participants provided written informed consent. 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][1]. 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]: http://ClinicalTrials.gov [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT02946346&atom=%2Fmedrxiv%2Fearly%2F2023%2F10%2F02%2F2023.09.30.23296382.atom