Vaginal Microbiota and Human Papillomavirus in Cervical Precancer and Cancer

Low and middle-income countries are confronting a significant public health challenge in the form of cervical cancer (CC). Disruptions in the cervicovaginal microbial community, especially reduced Lactobacillus dominance, have been linked with persistent human papillomavirus infection and heightened CC risk. Aim of our review is to systematically evaluate the association between the cervicovaginal microbiome, human papillomavirus persistence, and cervical neoplasia from existing systematic reviews and meta-analyses, while critically appraising their methodological quality. We conducted an overview of systematic reviews and meta-analyses examining associations between the cervicovaginal microbiome, HPV infection, and cervical neoplasia. Literature search was conducted across various databases, including Scopus, Clarivate, PubMed, and Google Scholar, systematically spanning the period from June 2010 to June 2025, to identify eligible systematic reviews and meta-analyses. The study protocol was prospectively registered in PROSPERO (CRD420250533647). The study included 23 systematic reviews and meta-analyses. According to the AMSTAR-2 assessment, most reviews had low methodological quality; 5 were rated critically low, the majority were low, while 2 were rated moderate. Heterogeneity in study design, sequencing platforms, population characteristics, and analytical methods limited comparability and precluded causal inference. Current evidence suggests a consistent association between cervicovaginal dysbiosis and HPV persistence or cervical lesion progression; however, the predominance of low-quality reviews and substantial methodological heterogeneity reduces confidence in the strength and direction of these associations. This study is the first comprehensive overview of systematic reviews and meta-analyses, guiding future priorities in microbiome research on cervical carcinogenesis. Well-designed longitudinal studies and standardized methodologies for the microbiome are needed to clarify temporality.