Cervicovaginal Microbiota and Biogenic Amine Metabolic Shifts in HPV-Associated Cervical Disease

Background: Cervical cancer is primarily caused by the human papillomavirus (HPV), with persistent infections progressing to low- (LGSIL) and high-grade (HGSIL) lesions. Emerging evidence indicates that the cervicovaginal microbiota influences HPV persistence and disease progression, although the underlying metabolic mechanisms remain unclear. Therefore, we assessed the relationship between the cervicovaginal microbiota and the metabolic milieu in women with cervical dysplasia and HPV infections. Methods: We recruited 36 non-menopausal, non-pregnant women who were classified as negative, LGSIL, or HGSIL based on pathology and HPV results. Cervical swabs were collected for genomic DNA extraction to characterize bacterial communities using 16S rRNA sequencing and to perform HPV genotyping. Cervical lavages were collected for untargeted metabolomic profiling using Gas Chromatography-Mass Spectrometry. Integrative multiomic analysis was performed using the MIMOSA2 pipeline. Results: Although bacterial community structure was not different between groups, women with HGSIL had higher richness and exhibited a higher abundance of Prevotella bivia, Prevotella buccalis, and Lachnospiraceae G-9 oral taxon 924. Lesion-positive samples had shifts in tyramine and putrescine, biogenic amines linked to cancer development. Specifically, Pseudomonas was identified as a potential contributor to tyramine oxidation. Conclusions: Cervical lesions and HPV risk are associated with shifts in the cervicovaginal microbial metabolic milieu, highlighting the role of low-abundant anaerobic bacteria. Despite the small sample size, biogenic amines were associated with anaerobic taxa and microbial dysbiosis. These findings warrant further assessment of microbial-derived metabolites and their potential to promote tumor progression by driving a pro-inflammatory, metabolically altered microenvironment.