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Original Investigation
January 11, 2018

Association of Oral Microbiome With Risk for Incident Head and Neck Squamous Cell Cancer

Author Affiliations
  • 1Department of Population Health, New York University School of Medicine, New York
  • 2NYU Perlmutter Cancer Center, New York University School of Medicine, New York
  • 3Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China
  • 4Department of Medicine, New York University School of Medicine, New York
  • 5Department of Epidemiology and Population Health, Albert Einstein College of Medicine, New York, New York
  • 6Departments of Pediatrics; Microbiology & Immunology; Obstetrics, Gynecology & Women’s Health, Albert Einstein College of Medicine, New York, New York
  • 7Department of Surgery, Memorial Sloan Kettering Cancer Center, New York
  • 8Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
  • 9Epidemiology Research Program, American Cancer Society, Atlanta, Georgia
  • 10Department of Pathology, New York University School of Medicine, New York
  • 11Department of Veterans Affairs New York Harbor Healthcare System, New York
JAMA Oncol. Published online January 11, 2018. doi:10.1001/jamaoncol.2017.4777
Key Points

Question  Is the prediagnostic oral microbiome associated with subsequent risk of head and neck squamous cell cancer (HNSCC)?

Findings  In this prospective study in 2 large well-established cohorts, oral commensal bacterial genera Corynebacterium and Kingella were associated with decreased risk for HNSCC.

Meaning  This first prospective study provides evidence that the commensal oral microbiome influences HNSCC risk, with potential implications for cancer prevention.

Abstract

Importance  Case-control studies show a possible relationship between oral bacteria and head and neck squamous cell cancer (HNSCC). Prospective studies are needed to examine the temporal relationship between oral microbiome and subsequent risk of HNSCC.

Objective  To prospectively examine associations between the oral microbiome and incident HNSCC.

Design, Setting, and Participants  This nested case-control study was carried out in 2 prospective cohort studies: the American Cancer Society Cancer Prevention Study II Nutrition Cohort (CPS-II) and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO). Among 122 004 participants, 129 incident patient cases of HNSCC were identified during an average 3.9 years of follow-up. Two controls per patient case (n = 254) were selected through incidence density sampling, matched on age, sex, race/ethnicity, and time since mouthwash collection. All participants provided mouthwash samples and were cancer-free at baseline.

Exposures  Oral microbiome composition and specific bacterial abundances were determined through bacterial 16S rRNA gene sequencing. Overall oral microbiome composition and specific taxa abundances were compared for the case group and the control group, using PERMANOVA and negative binomial generalized linear models, respectively, controlling for age, sex, race, cohort, smoking, alcohol, and oral human papillomavirus-16 status. Taxa with a 2-sided false discovery rate (FDR)-adjusted P-value (q-value) <.10 were considered significant.

Main Outcomes and Measures  Incident HNSCC.

Results  The study included 58 patient cases from CPS-II (mean [SD] age, 71.0 [6.4] years; 16 [27.6%] women) and 71 patient cases from PLCO (mean [SD] age, 62.7 [4.8] years; 13 [18.3%] women). Two controls per patient case (n = 254) were selected through incidence density sampling, matched on age, sex, race/ethnicity, and time since mouthwash collection. Head and neck squamous cell cancer cases and controls were similar with respect to age, sex, and race. Patients in the case group were more often current tobacco smokers, tended to have greater alcohol consumption (among drinkers), and to be positive for oral carriage of papillomavirus-16. Overall microbiome composition was not associated with risk of HNSCC. Greater abundance of genera Corynebacterium (fold change [FC], 0.58; 95% confidence interval [CI], 0.41-0.80; q = .06) and Kingella (FC, 0.63; 95% CI, 0.46-0.86; q = .08) were associated with decreased risk of HNSCC, potentially owing to carcinogen metabolism capacity. These findings were consistent for both cohorts and by cohort follow-up time. The observed relationships tended to be stronger for larynx cancer and for individuals with a history of tobacco use.

Conclusions and Relevance  This study demonstrates that greater oral abundance of commensal Corynebacterium and Kingella is associated with decreased risk of HNSCC, with potential implications for cancer prevention.

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