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
CIRB, CNRS, INSERM, Collège de France, Université PSL, Paris, France.
MIVEGEC, CNRS, IRD, Université de Montpellier, France.
PLoS Biol. 2025 Jan 21;23(1):e3002949. doi: 10.1371/journal.pbio.3002949. eCollection 2025 Jan.
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).
人乳头瘤病毒（HPV）感染导致每20例新增癌症病例中就有1例发病，给女性带来了特别沉重的负担。大多数肛门生殖器HPV感染在两年内会自行清除，但约10%的女性体内病毒持续存在的潜在机制仍 largely unknown。尽管如此，正是这些信息对于改进治疗、筛查和疫苗接种策略至关重要。为了解非持续性HPV感染中的病毒和免疫动态，我们开展了一项观察性纵向队列研究，频繁进行现场访视以收集生物样本。我们招募了189名年龄在18至25岁之间、于2016年至2020年居住在法国蒙彼利埃地区的女性。我们进行了974次现场访视，总计随访1619个月。我们收集了病毒载量、局部免疫细胞群体、细胞因子局部浓度和循环抗体滴度的数据。通过使用分层贝叶斯统计模型同时分析来自76名参与者的164次HPV感染数据，我们发现，在感染后的两个月内，非持续性感染中的HPV病毒载量达到一个平台期，平均持续13至20个月（95%可信区间），随后进入快速清除阶段。对HPV感染动态的这一首次描述还识别出了与感染清除相关的免疫关联因素，尤其是γδT细胞和CXCL10浓度。这项关于HPV动力学研究的一个局限性在于，许多感染随访被 censored。此外，一些免疫细胞群体难以标记，因为宫颈免疫的特征不如全身免疫那么明确。这些结果为理解急性和慢性感染之间的界限、控制HPV相关疾病以及开展感染源性人类癌症研究开辟了新的视角。试验注册：本试验已在ClinicalTrials.gov注册，注册号为NCT02946346。本研究已获得南地中海第一地区保护人类委员会（CPP Sud Méditerranée I，参考编号2016 - A00712 - 49）、健康研究领域信息处理咨询委员会（参考编号16.504）、国家信息与自由委员会（参考编号MMS/ABD/ AR1612278，决定编号DR - 2016 - 488）以及国家药品与健康产品安全局（参考编号20160072000007）的批准。
