Abstract 6617: Oral microbiome and subsequent risk for head and neck squamous cell cancer development
Authors: Kwak Soyoung , Usyk Mykhaylo , Wu Feng , Freedman Neal D. , Huang Wen-Yi , Mccullough Marji L. , Um Caroline Y. , Shrubsole Martha J. , Cai Qiuyin , Wang Chan , Li Huilin , Ahn Jiyoung , Hayes Richard B. 
Published: March 2024

Abstract
Background: The oral microbiota may be involved in head and neck squamous cell cancer (HNSCC) etiology, yet current evidence is largely limited to bacterial 16S amplicon sequencing or small retrospective case-control studies. We tested whether any oral bacteria and/or fungi influence the subsequent risk of HNSCC development.
Methods: We conducted a prospective case-control study nested within three epidemiological cohorts: the ACS-Cancer Prevention Study-II Nutrition Cohort (ACS-CPS-II), the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO), and the Southern Community Cohort Study (SCCS). Among 159,840 cohort participants, 236 individuals developed HNSCC during an average of 5.1 years of follow-up, and 485 controls who remained HNSCC-free were selected by 2:1 frequency matching, by cohort, age, sex, race/ethnicity, and time since mouthwash collection. All participants provided mouthwash samples and were cancer-free at baseline. We characterized the oral bacterial microbiome, using whole-genome shotgun sequencing, and the oral fungal microbiome, using ITS sequencing. We assessed relative abundance of microbiome-wide bacterial and fungal taxa for association with HNSCC by ANCOM-BC analysis. We also evaluated selected oral pathogen complexes for association with HNSCC by logistic regression. A microbial risk score (MRS) for HNSCC risk was calculated from all risk-associated microbes.
Results: Overall microbiome diversity at baseline was not related to the subsequent risk of HNSCC; however, we found that 13 oral bacterial species were differentially associated with development of this disease (P&lt;0.05), including newly identified Prevotella salivae, Streptococcus sanguinis, Leptotrichia sp, and several species belonging to Beta- and Gamma-proteobacteria. Furthermore, a priori periodontal pathogen complexes were associated with a higher risk of HNSCC (“red/orange” complex, OR=1.06, 95% CI=1.00-1.12). We did not identify any fungal taxa associated with HNSCC risk. Together, an MRS constructed for risk-associated bacteria and bacterial periodontal complexes conferred a 50% increase in HNSCC risk, per standard deviation increase in the MRS (multivariate OR=1.50, 95% CI=1.21-1.85).
Conclusions: Our research yields compelling evidence that oral bacteria are a risk factor for the development of HNSCC. The identified bacteria and bacterial complexes hold promise for identifying high-risk individuals and may further lead to personalized prevention approaches for HNSCC.
Citation Format: Soyoung Kwak, Mykhaylo Usyk, Feng Wu, Neal D. Freedman, Wen-Yi Huang, Marji L. Mccullough, Caroline Y. Um, Martha J. Shrubsole, Qiuyin Cai, Chan Wang, Huilin Li, Jiyoung Ahn, Richard B. Hayes. Oral microbiome and subsequent risk for head and neck squamous cell cancer development [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6617.