Division of Adolescent and Young Adult Medicine, Department of Pediatrics, University of California, Los Angeles, Los Angeles, CA, United States.
Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, Crump Institute for Molecular Imaging, University of California, Los Angeles, Los Angeles, CA, United States.
Front Cell Infect Microbiol. 2020 Sep 25;10:569022. doi: 10.3389/fcimb.2020.569022. eCollection 2020.
Persistent human papillomavirus (HPV) infections is necessary for the development of cervical cancers. Consequently, understanding the biologic mechanisms resulting in clearance is key in cancer prevention. Similar to other mucosal sites, it is expected that the local microbiome plays a significant role in shaping the immune response responsible for HPV clearance. Using cervical wash repository samples from a prospective study of HPV in women, this study investigates the microbiome and its associated inflammatory milieu during HPV 16 pre-acquisition, persistence and clearance states. For comparison, samples from women with no history of HPV ever during the study period were selected. We showed that 9 of 13 inflammatory cytokines were found to be significantly increased in the immediate post-clearance visit compared to the pre-acquisition or infection visits. was associated with higher levels of inflammatory cytokines. Women with no history of HPV infection had similar cytokine profiles as those with HPV 16 post-clearance. This study documented an immune response shortly after HPV 16 clearance. appeared to be involved in shaping this immune response. The appearance of may have resulted from a shift from anti-microbial to anti-viral immune response with loss of bacterial control. The similar high levels of cytokines seen in women with no history of HPV suggest that a certain level of inflammatory surveillance is required to maintain an HPV negative state. This data may inform therapies such as probiotics or pro-inflammatory agents for treatment of persistent HPV.
持续的人乳头瘤病毒 (HPV) 感染是宫颈癌发展的必要条件。因此，了解导致清除的生物学机制是癌症预防的关键。类似于其他粘膜部位，预计局部微生物组在塑造负责 HPV 清除的免疫反应方面发挥着重要作用。本研究使用来自 HPV 女性前瞻性研究的宫颈洗液库样本，研究了 HPV 16 前获得、持续和清除状态期间的微生物组及其相关炎症环境。为了进行比较，选择了在研究期间从未有过 HPV 史的女性的样本。我们发现，与前获得或感染就诊相比，13 种炎症细胞因子中有 9 种在清除后立即就诊时明显升高。 与更高水平的炎症细胞因子相关。没有 HPV 感染史的女性与 HPV 16 清除后的女性具有相似的细胞因子谱。本研究记录了 HPV 16 清除后不久的免疫反应。 似乎参与了这种免疫反应的形成。 的出现可能是由于抗微生物免疫反应向抗病毒免疫反应的转变，导致细菌失去控制。没有 HPV 感染史的女性中看到的细胞因子水平相似，这表明需要一定水平的炎症监测来维持 HPV 阴性状态。这些数据可能为治疗持续性 HPV 的治疗方法（如益生菌或促炎剂）提供信息。
