Objective: To understand characteristics of vaginal cervical microbiota in high-risk HPV (hrHPV) infected women and to uncover the relationship between hrHPV infection and vaginal cervical microbiota. Methods: All participants were randomly selected from Peking University First Hospital from September to October of 2017, including 5 subjects of control group, 5 cases of HPV16/18 group, 5 cases of other hrHPV infected group and 3 cases of cervical squamous carcinoma group. All subjects were required to fill in a questionnaire, and cervical and vaginal discharges were separately collected for microscopic examination and new generation sequencing targeting the variable region (V3-V4) of bacterial 16S rRNA gene. Results: Vaginal microbiota analysis: (1) 6 major phylum were found in vaginal microbiota:Firmicutes, Bacteroidetes, Fusobacteria, Actinobacteria, Tenericutes and Proteobacteria. Firmicutes contributed to the majority of normal vaginal flora, Bacteroidetes and Fusobacteria increased in hrHPV infected ones, while Fusobacteria showed significant difference in cervical carcinoma group. (2) Lactobacillus occupied most of normal vaginal flora while genus like Gardnella, Prevotella, Atopobium, Megasphaera and Sneathia increased in hrHPV infected subjects, Sneathia showed significant difference in cervical carcinoma group. (3) No significant difference had been calculated in Alpha diversity of four groups (P=0.073) . Cervical microbiota analysis: (1) Microbial diversity of cervical microbiota was higher than that of vaginal microbiota. (2) Significant difference had been found in Alpha diversity of four groups (P=0.046) . (3) Proteobacteria in normal cervical flora was much more than that in vagina, and Proteobacteria increased significantly in hrHPV infected cervical discharge. (3) Chlamydia increased significantly in cervical carcinoma group. Conclusions: The diversity of cervical microbiota is higher than that of vaginal microbiota. Change in cervical microbiota is more obvious than that of vagina in hrHPV infected subjects. Fusobacteria-Sneathia and Chlamydia significantly increase in cervical carcinoma group. Proteobacteria might relate to hrHPV infection.
目的： 了解高危型HPV感染妇女阴道菌群及子宫颈菌群的情况，探讨高危型HPV感染与阴道菌群及子宫颈菌群的关系。 方法： 选取2017年9月至10月北京大学第一医院妇产科就诊的患者（对照组5例，HPV16/18组5例，HPV其他高危型组5例，子宫颈癌组3例），填写调查问卷、行阴道及子宫颈分泌物微生态检测，同时使用新一代测序技术扩增细菌16S rRNA基因V3~V4高变区行菌群分析。 结果： 阴道菌群分析结果：（1）阴道菌群主要有6个菌门：厚壁菌门、放线菌门、拟杆菌门、变形菌门、梭菌门及软壁菌门，正常阴道菌群以厚壁菌门为主，高危型HPV感染者拟杆菌门、梭菌门增多，子宫颈癌组梭菌门显著增多；（2）正常阴道菌群在属水平以乳杆菌属为主，高危型HPV感染者乳杆菌减少，加德纳菌属、普雷沃菌属、阿托波菌属、巨球菌属及纤毛菌属增多，子宫颈癌组纤毛菌属显著增多；（3）高危型HPV感染后阴道菌群多样性增加，但4组阴道菌群Alpha多样性无显著性差异（P=0.073）。子宫颈菌群分析结果：（1）子宫颈菌群多样性高于阴道菌群；（2）高危型HPV感染者子宫颈菌群多样性明显增加，4组子宫颈菌群Alpha多样性有显著性差异（P=0.046）；（3）对照组子宫颈菌群较阴道菌群变形菌门增加，HPV感染后子宫颈变形菌门明显增加；（4）衣原体感染在子宫颈癌组明显增加。 结论： 子宫颈菌群多样性高于阴道菌群；高危型HPV感染者子宫颈菌群变化较阴道菌群更明显；梭菌门-纤毛菌属及衣原体与子宫颈癌相关，子宫颈变形菌门可能与高危型HPV感染相关。.
Keywords: Cervix uteri; High-throughput nucleotide sequencing; Microbiota; Papillomavirus infections; Vagina.