Oral Microbiome and Subsequent Risk of Head and Neck Squamous Cell Cancer

Study information

Needs review

study design

case-control

Citation

PMID PubMed identifier for scientific articles.

39325441

DOI Digital object identifier for electronic documents.

10.1001/jamaoncol.2024.4006

URI

Authors

Kwak S, Wang C, Usyk M, Wu F, Freedman ND, Huang WY, McCullough ML, Um CY, Shrubsole MJ, Cai Q, Li H, Ahn J, Hayes RB

Journal

JAMA oncology

Year

2024

IMPORTANCE: The oral microbiota may be involved in development of head and neck squamous cell cancer (HNSCC), yet current evidence is largely limited to bacterial 16S amplicon sequencing or small retrospective case-control studies. OBJECTIVE: To test whether oral bacterial and fungal microbiomes are associated with subsequent risk of HNSCC development. DESIGN, SETTING, AND PARTICIPANTS: Prospective nested case-control study among participants providing oral samples in 3 epidemiological cohorts, the American Cancer Society Cancer Prevention Study II Nutrition Cohort, the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, and the Southern Community Cohort Study. Two hundred thirty-six patients who prospectively developed HNSCC were identified during a mean (SD) of 5.1 (3.6) years of follow-up. Control participants who remained HNSCC free were selected by 2:1 frequency matching on cohort, age, sex, race and ethnicity, and time since oral sample collection. Data analysis was conducted in 2023. EXPOSURES: Characterization of the oral bacterial microbiome using whole-genome shotgun sequencing and the oral fungal microbiome using internal transcribed spacer sequencing. Association of bacterial and fungal taxa with HNSCC was assessed by analysis of compositions of microbiomes with bias correction. Association with red and orange oral pathogen complexes was tested by logistic regression. A microbial risk score for HNSCC risk was calculated from risk-associated microbiota. MAIN OUTCOMES AND MEASURES: The primary outcome was HNSCC incidence. RESULTS: The study included 236 HNSCC case participants with a mean (SD) age of 60.9 (9.5) years and 24.6% women during a mean of 5.1 (3.6) years of follow-up, and 485 matched control participants. Overall microbiome diversity at baseline was not related to subsequent HNSCC risk; however 13 oral bacterial species were found to be differentially associated with development of HNSCC. The species included the newly identified Prevotella salivae, Streptococcus sanguinis, and Leptotrichia species, as well as several species belonging to beta and gamma Proteobacteria. The red/orange periodontal pathogen complex was moderately associated with HNSCC risk (odds ratio, 1.06 per 1 SD; 95% CI, 1.00-1.12). A 1-SD increase in microbial risk score (created based on 22 bacteria) was associated with a 50% increase in HNSCC risk (multivariate odds ratio, 1.50; 95% CI, 1.21-1.85). No fungal taxa associated with HNSCC risk were identified. CONCLUSIONS AND RELEVANCE: This case-control study yielded compelling evidence that oral bacteria are a risk factor for HNSCC development. The identified bacteria and bacterial complexes hold promise, along with other risk factors, to identify high-risk individuals for personalized prevention of HNSCC.

Experiment 1

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Needs review

Curated date: 2024/12/05

Curator: Tosin

Revision editor(s): Tosin

Subjects

Location of subjects: United States of America

Host species Species from which microbiome was sampled. Contact us to have more species added.: Homo sapiens

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology: Saliva Sailva normalis,Saliva atomaris,Saliva molecularis,Salivary gland secretion,Saliva,saliva

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: Head and neck squamous cell carcinoma carcinoma of the head and neck,craniocervical region squamous cell carcinoma,head and neck squamous cell carcinoma,HNSCC,SCCHN,squamous cell carcinoma of head and neck,squamous cell carcinoma of the head and neck,squamous cell carcinoma, head and neck,squamous cell carcinomas of head and neck,Head and neck squamous cell carcinoma

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Healthy Controls

Group 1 name Corresponds to the case (exposed) group for case-control studies: ACS-CPS-II (American Cancer Society Cancer Prevention Study II)

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Participants from American Cancer Society cancer prevention Study II Nutrition Cohort.

Group 0 sample size Number of subjects in the control (unexposed) group: 106

Group 1 sample size Number of subjects in the case (exposed) group: 55

Lab analysis

Sequencing type: WMS

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: Not specified

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: Illumina

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).: relative abundances

MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?: Yes

Matched on Factors on which subjects have been matched on in a case-control study: age, ethnic group, time, race, sex, Matched on: "cohort" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.cohort

Alpha Diversity

Pielou Quantifies how equal the community is numerically: unchanged

Shannon Estimator of species richness and species evenness: more weight on species richness: unchanged

Richness Number of species: decreased