Abstract IA049: Genomic diversity, sociomicrobiome determinants, and immunomodulatory role of fannyhessea in HPV, dysplasia, and cervical cancer among Arizona cohorts

Abstract

While the emerging sociomicrobiome framework explains how lived experiences and social conditions shape microbial ecosystems and influence disease risk, the direct causal contributions of specific cervicovaginal bacteria, such as Gardnerella, Fannyhessea, and Sneathia, to HPV persistence and cervical carcinogenesis remain unclear. Further, higher rates of cervical cancer (CC) disproportionately affect Hispanic and Native American women with persistent human papillomavirus (HPV) infection, with cervicovaginal microbiome being an underrecognized contributing factor in addition to broader structural determinants of health. Fannyhessea species are key bacteria linked to bacterial vaginosis (BV), HPV persistence, and progression to CC. We hypothesized that social determinants influence Fannyhessea carriage and that genomic diversity within Fannyhessea drives distinct pathogenicity and host immune responses that contribute to HPV persistence and progression to CC. Thus, we utilized clinical, genomic, and in vitro studies to decipher role of Fannyhessea species in HPV infection and CC. The study analyzed two Arizona-based patient cohorts, comparing individuals with cervical pathology, diagnosed HPV infection, and patients undergoing routine annual woman’s exams. We analyzed 16S rRNA microbiome, immunoproteome, and HPV genotyping data from these patients' cervicovaginal samples and assessed clinical and sociodemographic associations. We also infected 3D human cervical epithelial cell models with representatives of three Fannyhessea species to assess epithelial-derived immune responses and performed comparative genomic analyses of Fannyhessea genomes. Fannyhessea vaginae was the most prevalent species in both cohorts, with an average of 50%, followed by Fannyhessea species type 2 (21%) and then Fannyhessea massiliense (20%). Integrating sociomicrobiome factors revealed that high parity, increased household size, and no higher education background were associated with Fannyhessea carriage, cervicovaginal dysbiosis, and HPV status. Native American and Hispanic patients had higher Fannyhessea carriage compared to White and non-Hispanic counterparts. Fannyhessea carriage correlated with elevated vaginal pH and increased species richness. In a clinical cohort, Fannyhessea were associated with elevated levels of proinflammatory, immune checkpoint, and cancer-associated immune markers. In vitro analyses revealed similar epithelial-derived immune profiles among the three Fannyhessea species. Genomic analyses identified species-specific protein families related to antibiotic resistance, potential barrier disruption, virulence, and niche adaptation. Clinical and laboratory studies determined that Fannyhessea act as emerging cervicovaginal pathogens, triggering inflammation and oxidative stress that can advance CC. This work highlights how social determinants shape microbial risk factors and underscores the potential of targeted, microbiome-based interventions to reduce CC disparities among high-risk and underserved populations. Nicole Jimenez, Pawel Laniewski, Melissa Herbst-Kralovetz. Genomic diversity, sociomicrobiome determinants, and immunomodulatory role of fannyhessea in HPV, dysplasia, and cervical cancer among Arizona cohorts [abstract]. In: Proceedings of the 19th AACR Conference on the Science of Cancer Health Disparities; 2026 Oct 18-21; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2026;35(10 Suppl):Abstract nr IA049.