Department of Laboratory Medicine, Qingdao Central Hospital, Qingdao, China.
Department of Laboratory Medicine, Qingdao Central Hospital, Qingdao, China.
Microb Pathog. 2021 Mar;152:104617. doi: 10.1016/j.micpath.2020.104617. Epub 2020 Nov 15.
HPV persistent infection is a main event leading to the development of cervical intraepithelial neoplasia and cervical cancer. Earlier to distinguish HPV persistent and transient infection is meaningful but the methods are limited. This study used 16S rDNA sequencing to determine the cervicovaginal microbiota of HPV persistent infection, transient infection and health women. Sequences analysis was performed and according to subsequent statistical analysis, the structure of cervicovaginal microbiota of healthy and transient infection individuals is relatively single, Firmicutes occupy the main composition. However, that of the HPV persistent infection presented a complicated trend and the abundance of Proteobacteria, Actinobacteria, Bacteroidetes and Fusobacteria was higher. The significance p-values of the average species abundance of Firmicutes, Proteobacteria and Bacteroides between HPV persistent and transient infection groups were 0.003, 0.018 and 0.005, respectively. The study also found 36 biomarkers of cervicovaginal microbiota dysbiosis for LDA score>4 among different groups. At genus level, Prevotella, Sphingomonas and Anaerococcus correlated with HPV persistent infection. At species level, Lactobacillus iners correlated with HPV transient infection. Besides, local immune microenvironment was changed with cervicovaginal microbiota dysbiosis. Interleukin-6 and TNF-α were significantly upregulated in cervical secretions from HPV persistent infection compared with those from transient infection and healthy women. Peripheral blood Regulatory T cells and myeloid-derived suppressor cells in patients with HPV persistent infection were also significantly increased. In conclusion, this study identified cervicovaginal microbiota dysbiosis closely related to HPV persistent infection, which provided a new idea and method for the prevention of cervical cancer.
HPV 持续感染是导致宫颈上皮内瘤变和宫颈癌发展的主要事件。早期区分 HPV 持续感染和一过性感染具有重要意义，但方法有限。本研究采用 16S rDNA 测序技术，确定 HPV 持续感染、一过性感染和健康女性的宫颈阴道微生物群。进行序列分析，根据后续统计分析，健康和一过性感染个体的宫颈阴道微生物群结构相对单一，厚壁菌门占主要成分。然而，HPV 持续感染的结构则呈现复杂趋势，变形菌门、放线菌门、拟杆菌门和梭杆菌门的丰度较高。HPV 持续感染和一过性感染组中厚壁菌门、变形菌门和拟杆菌门的平均物种丰度的显著性 p 值分别为 0.003、0.018 和 0.005。本研究还发现，HPV 持续感染和一过性感染组间 LDA 评分>4 的宫颈阴道微生物群失调的 36 种生物标志物。在属水平上，普雷沃氏菌属、鞘氨醇单胞菌属和厌氧球菌属与 HPV 持续感染相关。在种水平上，阴道加德纳菌与 HPV 一过性感染相关。此外，随着宫颈阴道微生物群失调，局部免疫微环境发生改变。与 HPV 一过性感染和健康女性相比，HPV 持续感染患者宫颈分泌物中的白细胞介素-6 和肿瘤坏死因子-α明显上调。HPV 持续感染患者外周血调节性 T 细胞和髓源抑制细胞也明显增加。综上所述，本研究确定了与 HPV 持续感染密切相关的宫颈阴道微生物群失调，为宫颈癌的预防提供了新的思路和方法。
