Abstract B139: Body mass index modulates vaginal microbial diversity and pathogenic signatures in HPV-related cervical disease

Abstract Background: The cervicovaginal tract is the least diverse niche of the human body. Its bacterial community is dependent upon the relative abundance of lactobacilli, which is simplified into five community state types (CSTs) depending on core species dominance. Various exogenous and endogenous factors—including genetics, Body Mass Index (BMI), sexual behavior, and human papillomavirus (HPV) infection—can alter the vaginal microbiota. Given that BMI has been shown to influence systemic inflammation and hormone levels—which can affect mucosal environments—we examined its impact on the vaginal microbiota in Hispanic women across different levels of HPV infection risk and cervical dysplasia. Methods: Cervicovaginal swabs were collected from 339 women as per IRB Streamlyne #2290033153. Samples underwent genomic DNA extraction for microbial assessment using 16S rRNA gene sequencing and for HPV genotyping using SPF10-LiPA. Following bioinformatic universal pipelines in QIITA, QIIME2, and RStudio, the cohort was rarefied at a sequencing depth of 1,521 reads and classified with the Greengenes2 extended library. Participants were characterized for BMI and their cervical phenotype corresponding to a clinical interpretation of cervical cytology in combination with HPV risk genotyping. Results: Participants in this cohort were between 21 and 60 years of age. Among underweight women who were negative for intraepithelial lesions but positive for high-risk HPV (NILMhrHPV+), microbial diversity was notably lower. Conversely, overweight women with low-grade squamous intraepithelial lesions (LGSIL) exhibited the highest microbial diversity. Overweight women with high-grade lesions (HGSIL) had elevated levels of Gardnerella. In women of normal weight diagnosed with HGSIL, the vaginal microbiota showed the lowest abundance of Lactobacillus crispatus and was significantly different from that of obese women with NILM (p=0.025), suggesting that shifts in microbial composition related to disease may occur independently of BMI. In contrast, obese women with HGSIL displayed the highest levels of Gardnerella vaginalis, the lowest levels of L. crispatus, and significantly reduced microbial richness compared to their NILM counterparts (p=0.0286), indicating a marked loss of diversity associated with disease progression. Conclusions/Future Directions: While BMI appears to influence microbial diversity and specific taxa such as Gardnerella vaginalis and Lactobacillus crispatus, our data suggests that disease-associated microbial shifts can occur independently of body weight. Notably, the loss of protective Lactobacillus species and increase of potentially pathogenic bacteria were most pronounced in women with high-grade lesions, particularly among those who were obese. This underscores the importance of considering host metabolic status and microbial profiles in the context of HPV persistence and cervical disease progression. Further studies are warranted to explore the mechanistic links between host factors, microbiome dynamics, and cervical carcinogenesis. Citation Format: Saadia Jiménez-Ñeco, Natalie M. Meléndez-Vázquez, Jemilly Salas-Cruz, Kvrismar González Castillo, Desiré Vázquez Ortiz, Josefina Romaguera Agrait, Filipa Godoy-Vitorino. Body mass index modulates vaginal microbial diversity and pathogenic signatures in HPV-related cervical disease [abstract]. In: Proceedings of the 18th AACR Conference on the Science of Cancer Health Disparities; 2025 Sep 18-21; Baltimore, MD. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(9 Suppl):Abstract nr B139.