The Interplay Between Cervicovaginal Microbiota Diversity, Lactobacillus Profiles and Human Papillomavirus in Cervical Cancer: A Systematic Review.

Background and Objectives: Interest in defining the characteristics of the cervicovaginal microbiota (CVM) in invasive cervical cancer (ICC) is growing, particularly concerning Lactobacillus species, as evidence suggests that these may differ in affected women and potentially interact with Human Papillomavirus (HPV) infection. Understanding these features could have important implications for disease management. Thus, this study aims to systematically review the main characteristics of available literature exploring the relationship between CVM diversity, Lactobacillus profiles, and HPV in ICC; Methods: A comprehensive bibliographic search was conducted across databases, including Medline, Embase, Scopus, the Cochrane Database of Systematic Reviews, and ClinicalTrials.gov, in accordance with the to the PRISMA guidelines. The review included studies that met the following inclusion criteria: studies comparing CVM in women with ICC to controls, focusing on Community State Types (CSTs), Lactobacillus profiles, and microbial diversity. Exclusion criteria included commentaries, letters, reviews, and studies without control groups. Variables were analyzed using the Kruskal-Wallis and Fisher's exact tests, with statistical significance level set at 0.05. Data analysis was conducted and reviewed in a blinded manner. Results: A total of 28 studies published between 2015 and 2024 met the inclusion criteria. A total of 2082 patients were included, with 323 (41.9%) of the 770 cases testing positive for HPV and 327 (24.9%) of the 1312 controls testing positive for HPV. A total of 18 studies specifically examined HPV genotypes. Cervical swabs were employed in 19 out of 28 studies (67.9%), while vaginal swabs were used in 17 studies (60.7%). Additionally, two studies included samples collected via cervical biopsy (7.1%), four studies utilized cervicovaginal lavage (14.3%), and one study used a cervical brush for sample collection (3.6%). Regarding microbiota profiling, 26 studies (92.9%) employed 16S rRNA analysis, while one study (3.6%) utilized whole-genome sequencing (WGS), and another (3.6%) used 16s rDNA. A total of 10 studies (35.7%) examined the distribution of CSTs. Five studies (17.9%) reported on Lactobacillus profiles. Different levels of Lactobacillus crispatus and Lactobacillus iners were observed, along with variations between Lactobacillus-dominant and Lactobacillus-depleted communities. A total of 22 studies (78.6%) assessed α-diversity, and 17 studies (60.7%) examined β-diversity; Conclusions: This study emphasizes the heterogeneous features of the studies exploring the association between alterations in the CVM, HPV, and the development of ICC, suggesting the need for further research to better understand this relationship. These findings could inform new strategies for prevention and treatment.