Exploring the Vaginal Microbiome's Role in HPV Infection Dynamics: A Prospective Cohort Study

Abstract Background The incidence of cervical cancer is often associated with the persistent infection of Human Papillomavirus (HPV). Identifying biomarkers that can monitor the progression of HPV infection and predict the likelihood of developing high-risk disease states in the early stages of HPV infection is crucial. We hypothesize that the composition of the vaginal microbiome plays a key role in the dynamic changes associated with HPV infection. Thus, the aim of this study is to explore the dynamic changes in microbiome characteristics across different HPV infection outcomes. Methods In this prospective observational cohort study, high-throughput 16S ribosomal RNA (16S rRNA) sequencing technology was employed to comprehensively analyze the characteristics and community composition of the vaginal microbiome (VMB) among 96 Chinese women. Participants were divided into three groups: 1. The persistent infection cohort, consisting of 22 patients with ongoing HPV infections; 2. The transient infection cohort, including 31 patients who had successfully cleared high-risk human papillomavirus (HR-HPV) infections; and 3. The control group, comprising 43 healthy females. Results At the onset of HPV infection, compared to the control group（CG）, the infected group exhibited a lower abundance of Lactobacillus and a significantly higher abundance of Pseudomonas, Bifidobacterium, Limosilactobacillus, Peptostreptococcus, Gardnerella, Prevotella, and Dialister. At the study's endpoint, the abundance of Prevotella in the HPV clearance group（HCG）was significantly higher than the control group, whereas the abundances of Bifidobacterium, Limosilactobacillus, and Peptostreptococcus in the persistent HPV infection group（PHIG） were significantly higher than those in both HC group and control group. Both PHI group and HC group exhibited distinct vaginal microbiome characteristics. The PHI group was characterized by a decrease in Lactobacillus and a significant increase in Bifidobacterium, Limosilactobacillus, and Peptostreptococcus over time. Conversely, the HC group showed an increase in Pseudomonas and a decrease in Prevotella and Peptostreptococcus. Furthermore, KEGG pathway enrichment analysis reveals significant variations in gene functions and metabolic processes, especially in lipid biosynthesis, as HPV infection persists. This increased lipid metabolism suggests that interactions between the virus and host could drive the pathological development and persistence of HPV by altering pathways of lipid synthesis and degradation. Conclusion The observed interplay and mutual regulation between microbial communities suggest that a delicate balance is essential for maintaining cervical health. Disruption of this microbial equilibrium can lead to cervical lesions and potentially result in carcinogenesis. These insights underscore the importance of understanding the microbial ecology within the vaginal environment, as they have profound implications for developing targeted prevention strategies and personalized medical interventions, particularly for high-risk populations. Therefore, maintaining or restoring the microbial balance could be pivotal in preventing cervical pathologies, indicating a promising avenue for future research and clinical applications in the field of gynecological health. Retrospectively registered This study was approved by the Ethics Committee of the Beijing Chaoyang Hospital affiliated with the Capital Medical University (NO.2023-S-415).