Cytokine response following perturbation of the cervicovaginal milieu during HPV genital infection

Human papillomaviruses (HPVs) are the most oncogenic viruses known to human, causing nearly all cervical cancers worldwide. Highly prevalent in young, sexually active women, most HPV infections are cleared within 3 years, and only a minority of those infections persist and lead to cancer later in life. To better characterize the immuno-modulatory impact of early HPV infection and more generally perturbations of the cervicovaginal milieu, we measured changes in a panel of 20 cytokines, known as highly dynamic effector molecules implicated in cell signaling. We analyzed 92 cervicovaginal samples collected from young, sexually active women who were tested for or diagnosed with HPV, chlamydia, and bacterial vaginosis. Also, symptoms associated with genital inflammation and infection were collected through self-reporting. Following a parsimonious multi-factor modeling approach, our statistical analyses revealed that increased IL-1Alpha and IL-12/IL-23p40 concentrations were associated with HPV infection. Cytokine network analysis further highlighted the role of IL-1Alpha and macrophage inflammatory proteins (MIP-3Alpha) in HPV-associated immuno-modulation. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program [grant agreement No 648963 to Samuel Alizon]. The sponsor had no role in 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 is promoted by the Centre Hospitalier Universitaire de Montpellier and has been approved by the Comite de Protection des Personnes (CPP) Sud Mediterranee I on 11 May 2016 (CPP number 16 42, reference number ID RCB 2016-A00712-49) by the Comite Consultatif sur le Traitement de l'Information en matiere de Recherche dans le domaine de la Sante on 12 July 2016 (reference number 16.504) and by the Commission Nationale Informatique et Libertes on 16 December 2016 (reference number MMS/ABD/AR1612278 decision number DR-2016-488). This trial was authorised by the Agence Nationale de Securite du Medicament et des Produits de Sante on 20 July 2016 (reference20160072000007). The ClinicalTrials.gov identifier is [NCT02946346][1]. All participants provided written informed consent. All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. 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 and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Scripts and data will be deposited in the Zenodo repository. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT02946346&atom=%2Fmedrxiv%2Fearly%2F2021%2F02%2F16%2F2021.02.10.21251486.atom