Vaginal dysbiosis and the risk of human papillomavirus and cervical cancer: systematic review and meta-analysis

OBJECTIVE: The vaginal microbiota proposedly influence the association between human papillomavirus and cervical cancer. Our aim was to assess whether vaginal dysbiosis affects human papilloma virus acquisition, persistence, and progression to related cervical premalignancy. DATA SORUCES: MEDLINE, Embase, CINAHL, Cochrane Library, and Web of Science (inception until June 2018) were used for this study. The study protocol was registered at PROSPERO (CRD42016035620). STUDY ELIGIBILITY CRITERIA: This systematic review included all observational studies reporting on incident human papilloma virus, persistent human papilloma virus, and/or related cervical disease in women with or without vaginal dysbiosis prior to outcome assessment. STUDY APPRAISAL AND SYNTHESIS METHODS: We used random- effects models for meta- analyses and report pooled relative risks with 95% confidence intervals. The risk for incident and/or persistent human papilloma virus or related cervical disease based on longitudinal results was determined. RESULTS: Of 1645 unique articles, 15 mainly prospective cohort studies were included, published between 2003 and 2017, including a total of 101,049 women. Vaginal dysbiosis was associated with an increased risk of incident human papilloma virus (overall relative risk, 1.33, 1.18-1.50, I-2 = 0%; among young women relative risk, 1.43, 1.10-1.85, I-2 = 0%), human papilloma virus persistence (overall relative risk, 1.14, 1.01-1.28, I-2 = 44.2%; for oncogenic types relative risk, 1.18, 1.01-1.38, I-2 = 0%), and high- grade lesions and cancer (relative risk, 2.01, 1.40-3.01, I-2 = 0%), but women with lesions/cancer were compared with those without, regardless of their oncogenic human papilloma virus status. Overall, comparable results were found in the molecular vaginal microbiota studies. CONCLUSION: This study supports a causal link between vaginal dysbiosis and cervical cancer along the oncogenic human papillomavirus acquisition, persistence, and cervicovaginal dysplasia development pathway.