Abstract

Abstract The vaginal microbiome can impact gynecologic health and disease. It is still unclear the extent to which the microbiome plays in the progression and development of gynecologic cancers. Fannyhessea vaginae is a key vaginal bacterium linked to bacterial vaginosis, HPV acquisition, and cervical cancer. F. vaginae was recently proposed for reclassification as three species: F.vaginae, Fannyhessea massiliense, and Fannyhessea species type 2. We hypothesize that these Fannyhessea species vary in terms of their host-microbe interactions which contribute to cancer progression/severity. We investigated the prevalence of Fannyhessea species in two of our Arizona-based HPV and cervical cancer cohorts recruited in Phoenix or Flagstaff area. The Phoenix (Phx) cohort included: women diagnosed with invasive cervical cancer (ICC=9), high-grade squamous intraepithelial lesion (HSIL=27), and low-grade squamous intraepithelial lesion (LSIL=11), as well as controls who were either HPV-positive=20 or HPV-negative without dysplasia=31. While the Flagstaff cohort (Flg) consisted of 31 women that were HPV-positive=7 or HPV-negative=24. The 16S rDNA sequencing information was analyzed with DADA2 and QIIME2 to identify the microbial composition of the cervicovaginal profiles of these patients. Statistical analyses are ongoing, utilizing survey data on these species to decipher their clinical associations with factors such as HPV status and genotype. The cohorts had a prevalence of 59.2% of Atopobiaceae bacteria in Phx and 38.7% prevalence in Flg cohort. We observed F. vaginae (50% and 38.7%, respectively), Fannyhessea species type 2 (16.4% and 25.0%, respectively), F. massiliense (21.0% and 18.8%, respectively) in these cohorts. Interestingly, in both dysplasia groups of the Phx cohort these species had an increased abundance, but it did not reach significance. Other clinical and demographic factors in both cohorts, vaginal pH (p = 0.0005 and 0.47, respectively), Native American race (p=0.002) and Hispanic ethnicity (p= 0.013 and 0.63, respectively), indicated significant species-specific differences in the prevalence of Atopobiaceae. Additionally, genital inflammation scores were higher in profiles that contained Atopobiaceae species (p= 0.05) in Phoenix cohort. In addition, microbial co-occurrence analysis identified that Fannyhessea species highly co-occurred with one another. Sneathia amnii, Sneathia sanguinegens, and other BV-associated bacteria also co-occurred with Fannyhessea species, indicating an association between multiple Fannyhessea species and a potential link to cancer that requires further investigation. This research highlights potential associations of BV-associated bacteria and their role in HPV infection and cervical cancer and investigates the relationship of underexplored Fannyhessea species in historically understudied populations that have the highest disease burden. The overall data from our study provide foundational knowledge on putative oncogenic bacteria that could be exploited to modulate the microbiome and improve cancer outcomes. Citation Format: Nicole R. Jimenez, Paweł Łaniewski, Naomi R. Lee, J. Gregory Caporaso, Melissa M. Herbst-Kralovetz. Newly identified Fannyhessea species contributions in HPV infection, cervical dysplasia, and cancer in two Arizonan cohorts [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C091.

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