Abstract PR016: Viewing Native American cervical cancer disparities through the lens of the vaginal microbiome: A pilot study
Authors: Laniewski Pawel , Joe Tawnjerae R. , Eddie Tristen L. , Bordeaux Skyler J. , Quiroz Verity , Peace Donna J. , Caporaso J. Gregory , Lee Naomi R. , Herbst-Kralovetz Melissa M. 
Published: December 2023

Abstract
Cervical cancer disproportionally affects Native American (NA) women who have higher rates of cervical cancer, are often diagnosed at later stages and are more likely to die from the disease compared to White women. This cancer disparity is primarily attributed to a lack of screening and unequal access to healthcare; however, other factors in NA women might contribute. Vaginal dysbiosis has been implicated in persistent HPV infection and cervical cancer. Yet, there is a paucity of data on the HPV infection patterns and the vaginal microbiota composition in NA communities. Here, we aimed to elucidate the relationships between HPV, microbiome, and genital inflammation to better understand how these factors relate to increased cervical cancer risk in NA women. In this cross-sectional study, we enrolled 31 women at the Native American for Community Action clinic (Flagstaff, AZ). Participants provided two self- or physician-collected vaginal swabs. Vaginal pH was also measured. One vaginal swab was used for DNA extraction and subsequent HPV genotyping and 16S rRNA gene sequencing. The microbiome analysis was conducted using QIIME 2. Levels of 48 immune mediators in the second vaginal swab were quantified by Bio-Plex. Most participants identified as American Indian or Alaska Native (n=16), White (n=11) or Hispanic (n=5). The average age was 29 years old (ranging from 18 to 46). High-risk HPV genotypes (HPV 39, 45, 52, 53, 58, 59) were detected in 23% of women (5 NA and 2 non-NA). Intriguingly, the current nonavalent HPV vaccine does not target half of genotypes detected in this cohort. Vaginal microbiota profiles were dominated by Lactobacillus in 56% of NA women, which was similar to levels observed in non-NA participants but overall lower than in previously reported non-Hispanic White cohorts. The most prevalent Lactobacillus species included L. crispatus (associated with optimal health) and L. iners (considered non-optimal). Lactobacillus-depleted profiles consisted of typical communities of anaerobes associated with bacterial vaginosis: Gardnerella, Fannyhessea, Prevotella, and Sneathia. Lactobacillus dominance was highly associated with low (≤4.5) vaginal pH (p=0.0017). Moreover, HPV-positive women tended to have lower Lactobacillus abundance compared to HPV-negative women, though this relationship was not statistically significant (p=0.07). Immune marker profiles also related to the vaginal microbiota composition with proinflammatory cytokines (IL-1beta, IL-12, IL-15 and TNFalpha) being significantly elevated (p&lt;0.05) in women with Lactobacillus depletion. In addition, GM-CSF levels were decreased in women with Lactobacillus depletion, as well as in HPV-positive women. In conclusion, our pilot study suggests an interplay between HPV, vaginal microbiota and host defense may play a role in cervical cancer health disparity among NA women. Future longitudinal studies are ongoing to determine the mechanistic role of vaginal microbiota in HPV persistence, toward the long-term goal of reducing health disparities between White and NA populations.
Citation Format: Pawel Laniewski, Tawnjerae R. Joe, Tristen L. Eddie, Skyler J. Bordeaux, Verity Quiroz, Donna J. Peace, J. Gregory Caporaso, Naomi R. Lee, Melissa M. Herbst-Kralovetz. Viewing Native American cervical cancer disparities through the lens of the vaginal microbiome: A pilot study [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 PR016.