Associations of Cervical Vaginal Microflora with HPV Infection, Cervical Intraepithelial Neoplasia and Cancer: A Systematic Review and Network Meta-Analysis
目的：系统评价宫颈阴道微生物群与人乳头瘤病毒(human papillomavirus, HPV)感染、宫颈上皮内瘤变(cervical intraepithelial neoplasias, CIN)和宫颈癌之间的关系。方法：用计算机检索PUBMED、EMBASE、COCHRANE LIBRARY等数据库2010年以来关于宫颈阴道微生物群与HPV感染、宫颈上皮内瘤变和宫颈癌之间的关系的研究，经过筛选后进行系统评价，采用Stata/MP 16.0软件对文献进行网络荟萃分析(network meta-analysis, NMA)。结果：经筛选后共纳入12个研究，共涉及1449例受试者。12项研究中最常见的阴道微生物群落状态类型(community state type, CST)为CST I：卷曲乳杆菌优势的CST、CST III：惰性乳杆菌优势的CST和CST IV：乳酸杆菌缺乏的CST。Meta分析结果证实，阴道菌群以非乳酸杆菌为优势的女性更可能与HPV感染、高危HPV感染、宫颈病变或宫颈癌相关，其中发生HPV感染的合并优势比(odds ratio, OR)为1.78，95%CI (1.29, 2.47)，发生高危HPV感染OR = 1.36，95%CI (0.97, 1.88)，发生任何宫颈病变或癌症：OR = 2.10，95%CI (1.03, 4.27)；对于高危HPV感染的清除或CIN2的消退，非乳酸杆菌优势的CST优势比为0.39，95%CI (0.23, 0.66)；而卷曲乳杆菌优势的CST优势比为2.36，95%CI (1.23, 4.52)。任何HPV阳性组、高危HPV阳性组中低乳酸杆菌CST所占加权合并比例均为最高，分别为52%，95%CI (46%, 59%)和49%，95%CI (38%, 60%)。结论：女性宫颈阴道微生物群与人乳头瘤病毒(HPV)感染、宫颈上皮内瘤变和宫颈癌的发生发展密切相关，缺乏乳酸杆菌的CST是HPV感染和宫颈疾病、癌症发生的危险因素，而卷曲乳杆菌优势的CST可能促进高危HPV感染的清除并有利于宫颈上皮内瘤变的自然消退。 Objective: To systematically evaluate the associations of cervical vaginal microbiota with human papillomavirus (HPV) infection, cervical intraepithelial neoplasias (CIN), and cervical cancer (CC). Methods: Studies on the associations of cervical vaginal microbiota of HPV infection, cervical intraepithelial neoplasias and cervical cancer since 2010 were searched in PUBMED, EMBASE, COCRANE LIBRARY and other databases by computer. After screening, systematic evaluation was conducted. Stata/MP 16.0 software was used for network meta-analysis of literatures. Results: After screening, 12 studies were included, involving a total of 1449 subjects. The most common vaginal community State types (CSTs) in the 12 studies were CST I: L. crispatus-dominant CST, CST III: L. iners-dominant CST, and CST IV: non-Lactobacillus-dominated CST. Meta analysis results confirmed that the women with non-Lactobacillus-dominant CST are more likely to HPV infection, high-risk HPV infection, cervical lesion and cervical cancer, including the consolidation odds ratio of HPV infection, OR = 1.78, 95%CI (1.29, 2.47), odds ratio of high risk HPV infection, OR = 1.36, 95%CI (0.97, 1.88), odds ratio of any cervical intraepithelial lesion or cancer, OR = 2.10, 95%CI (1.03, 4.27); for the elimination of high-risk HPV infection and regression of CIN2, the non-lactobacilli- dominant CST shows odds ratio with OR = 0.39, 95%CI (0.23, 0.66). The L. crispatus-dominant CST shows odds ratio with OR = 2.36, 95%CI (1.23, 4.52). The weighted pooled proportion of LOW lactobacillus CST in any HPV-positive group and high-risk HPV-positive group was the highest, with 52%, 95%CI (46%, 59%) and 49%, 95%CI (38%, 60%), respectively. Conclusion: Cervical vaginal microbiota and human papilloma virus (HPV) infection, cervical intraepithelial neoplasia is closely related to the occurrence of cervical cancer development, low number of lactobacilli CST is HPV infection and cervical disease, cancer risk factors, and lactobacillus crispatus can promote high-risk HPV infection of the advantages of the removal and help the natural regression of cervical intraepithelial neoplasia.