Associations of Cervicovaginal Lactobacilli With High-Risk Human Papillomavirus Infection, Cervical Intraepithelial Neoplasia, and Cancer: A Systematic Review and Meta-Analysis

Background. Vaginal dysbiosis characterized by depleted lactobacilli is usually correlated with human papillomavirus (HPV) infection and cervical carcinogenesis, but the effect of the Lactobacillus genus and represented species on this process remains unclear. Methods. PubMed, EMBASE, and CENTRAL databases were searched up to February 15, 2019. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a fixed-effect model and Review Manager (version 5.3) for Mac. Results. Eleven studies comprising 1230 cases were included. Lactobacillus spp. was associated with the decreased detection of high-risk subtype (hr)HPV infection (OR = 0.64, 95% CI = 0.48-0.87, I-2 = 6%), cervical intraepithelial neoplasia (CIN) (OR = 0.53, 95% CI = 0.34-0.83, I-2 = 0%), and cervical cancer (CC) (OR = 0.12, 95% CI = 0.04-0.36, I-2 = 0%). At the level of Lactobacillus species, Lactobacillus crispatus, but not Lactobacillus iners, was correlated with the decreased detection of hrHPV infection (OR = 0.49, 95% CI = 0.31-0.79, I-2 = 10%) and CIN (OR = 0.50, 95% CI = 0.29-0.88, I-2 = 0%). Conclusions. Cervicovaginal Lactobacillus spp. is associated with the decreased detection of hrHPV infection, CIN, and CC; L. crispatus may be the critical protective factor.