研究目的：分析高危型HPV感染与阴道微生态失调之间的相关性，探讨高危型HPV感染、宫颈上皮内病变、宫颈癌患者的阴道菌群特征。研究方法：（1）回顾性分析2015年5月至2018年12月于北京清华长庚医院妇产科门诊就诊，同时行阴道微生态、高危型HPV检测患者的临床资料，分析HPV感染与阴道微生态失调的相关性；（2）采用16S rRNA高通量测序技术检测高危型HPV感染、宫颈上皮内病变、宫颈癌患者的阴道分泌物样本，并通过生物信息分析探讨其菌群特征。研究结果：（1）共纳入12281例患者临床资料进行回顾性分析，经阴道微生态检测诊断为各种阴道炎者3517例，HPV感染者1775例；经单因素logistc回归分析显示，阴道炎可增加高危型HPV感染风险，OR值1.277，95%CI[1.147，1.422]；其中需氧菌性阴道炎、细菌性阴道病及二者的混合感染均可增加 HPV感染风险，OR值及95%CI分别为1.332 [1.169，1.518]、1.845 [1.603，2.123]和1.915 [1.587，2.310]。而VVC、TV及其他类型混合感染时高危型 HPV感染风险无明显增加。（2）本研究第二部分共纳入103例患者进行阴道菌群特征分析，其中高危型HPV阴性者29例， HPV阳性者74例；经组织病理学结果证实为LSIL者17例；HSIL者15例；宫颈癌19例。高通量测序结果提示：HPV阴性者的阴道菌群以乳杆菌属表达为主，高危型HPV感染者较HPV阴性者相比，乳杆菌属表达减少，菌群多样性增加，细菌性阴道病相关菌群如阿托波菌属、普雷沃菌属、纤毛菌属、韦荣菌属、加德纳菌属等表达增加，需氧菌性阴道炎相关链球菌主要有无乳链球菌、咽峡炎链球菌表达增加；在HPV16、18型感染者中惰性乳杆菌的表达较非16、18型的HPV感染者明显增加；在宫颈癌患者中，乳杆菌表达进一步减少，菌群多样性进一步增加。综上，本研究结果提示，阴道炎与高危型HPV感染之间存在一定的相关性，尤其是需氧菌性阴道炎、细菌性阴道病及两者的混合感染；在高危型HPV感染者中，乳杆菌表达减少，菌群多样性增加，需氧菌性阴道炎、细菌性阴道病相关菌群表达增加。因此，建议临床中对高危型HPV感染者同时行阴道微生态检测，重视需氧菌性阴道炎、细菌性阴道病及混合性阴道炎的诊治；关于阴道菌群变化与高危型HPV感染及宫颈癌发生的相关作用机制仍需进一步的研究与探讨。

Objective: To analyze the correlation between high-risk HPV infection and vaginal microbiota disorder, and to explore the characteristics of vaginal flora in patients with high-risk HPV infection, cervical intraepithelial lesions and cervical cancer. Methods: (1)Retrospective analysis was made on the clinical data of patients with vaginal microecology and high-risk HPV detected in the outpatient department of gynecology and obstetrics of Beijing Tsinghua Changgung hospital from May 2015 to December 2018, and the correlation between HPV infection and vaginal microbiota disorder was analyzed; (2) 16S rRNA High throughput sequencing was used to detect vaginal flora of patients with high-risk HPV infection, cervical intraepithelial lesions, and cervical cancer. Results: (1) The clinical data of 12281 cases were enrolled. 3517 cases of vaginitis and 1775 cases of HPV infection were diagnosed by transvaginal microecological test. The single factor Logistic regression analysis showed that vaginitis could increase the risk of high-risk HPV infection,OR value was 1.277, 95% CI [1.147, 1.422]; including aerobic vaginitis, bacterial vaginosis and their Combined infection increased the risk of HPV infection,OR and 95% CI were 1.332 [1.169, 1.518], 1.845 [1.603, 2.123] and 1.915 [1.587, 2.310], respectively. However, there was no significant increase in the risk of high-risk HPV infection among VVC, TV and other types of mixed infection. (2) In the second part of this study, 103 patients were included to analyze the characteristics of vaginal flora, including 29 cases of high-risk HPV negative, 74 cases of HPV positive; 17 cases of LSIL confirmed by histopathological results; 15 cases of HSIL; 19 cases of cervical cancer. The results of high-throughput sequencing showed that in HPV negative patients, Lactobacillus is the documented microbiome, and compared to HPV negative ones, expression of the expression of Lactobacillus decreased, the microbial diversity increased, the expression of bacteria related to bacterial vaginosis increased, such as Atopobium, Prevotella, Sneathia, Veillonella, Gardnerella etc., and the expression of Streptococcus related to aerobic vaginitis mainly increased in HPV positive patients, especially Streptococcus anginosus and Streptococcus agalactiae . The expression of Lactobacilli inners was significantly higher in patients with HPV16、18 infection than that in patients with non type 16 and type 18 HPV infection.In patients with cervical cancer, the expression of Lactobacillus was further reduced, and the microbial diversity was further increased.To sum up, the results of this study suggest that there is a certain correlation between vaginitis and high-risk HPV infection, especially aerobic vaginitis, bacterial vaginosis and their mixed infection; In high-risk HPV infection, the expression of Lactobacillus decreased, the microbial diversity increased, and the expression of bacteria related to aerobic vaginitis and bacterial vaginosis increased. Therefore, it is suggested that the patients with high-risk HPV infection should be tested for vaginal microecology at the same time, and the clinicians have to pay attention to the diagnosis and treatment of aerobic vaginitis, bacterial vaginosis and mixed vaginitis. The mechanism of the correlation between the changes of vaginal flora and the high-risk HPV infection and cervical cancer still needs further study and discussion.