Oral bacteria a risk factor for HNSCC development

A prospective nested case-control study yields compelling evidence that oral bacteria are a risk factor for the development of head and neck squamous cell carcinoma (HNSCC), which comprises cancers of the oral cavity, pharynx, and larynx.

“In three large prospective cohorts including 159,840 individuals, we identified novel oral bacterial species, including both commensals and periodontal pathogenic bacterial complexes that together conferred a 50-percent increased risk of HNSCC,” said the researchers.

This study comprised participants who provided oral samples from 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. A total of 236 HNSCC case participants (mean age 60.9 years, 24.6 percent women) were identified during a mean follow-up of 5.1 years and 485 matched control participants. [JAMA Oncol 2024;10:1537-1547]

The overall microbiome diversity at baseline was not tied to subsequent HNSCC risk. However, 13 oral bacterial species were found to be associated with subsequent HNSCC risk. The species included the newly identified Prevotella salivae, Streptococcus sanguinis, and Leptotrichia species, and several species belonging to beta and gamma Proteobacteria.

According to the researchers, these results correlate with their earlier observations using 16S ribosomal RNA amplicon gene sequencing that, at the genera and class levels, Proteobacteria may be related to oral carcinogen metabolism. [JAMA Oncol 2018;4:358-365; ISME J 2016;10:2435-2446]

The red/orange periodontal pathogen complex was moderately associated with HNSCC risk (odds ratio [OR], 1.06 per 1 SD). A 1-SD increase in microbial risk score (created based on 22 bacteria) was associated with a 50-percent increase in HNSCC risk (multivariate OR, 1.50).

The red/orange oral pathogen complexes are associated with periodontal disease, which is a putative risk factor for head and neck cancer. [J Clin Periodontol 1998;25:134-144; Cancers (Basel) 2020;12:1893] “[Our findings strengthen] the hypothesis that oral health status is causally related to HNSCC development and, furthermore, indicates that well-characterized red/orange oral bacterial complexes may be involved early in head and neck carcinogenesis before HNSCC is overt,” the researchers explained.

There were no significant associations found between oral fungi and HNSCC risk. “It is plausible that oral fungi, as opportunistic pathogens, may influence … head and neck cancer development beyond the time frame of our prediagnostic sample collections,” they noted.

Hold promise as potential biomarkers

Recent studies have explored the role of other microbiota in HNSCC development. [Int J Mol Sci 2022;23:8323; Int J Cancer 2019;145:775-784; Oral Oncol 2023;137:106305] “Recognizing this, there is a critical need to more comprehensively identify novel microbial risk factors that could be used to help prevent HNSCC,” the researchers said.

“Our findings potentially reflect a subtle dysbiosis, years before clinical diagnosis in the oral microbiome, marked by the depletion of commensal organisms and enrichment of oral pathogens, leading to significant increases in HNSCC risk,” said the researchers.

The study may have been observational in nature, but the substantial sample size allowed for the evaluation of HNSCC subsites and association with alcohol intake and smoking.

“The identified bacteria and bacterial complexes and the associated microbial risk score hold promise as potential biomarkers, along with other risk factors, to identify high-risk individuals for personalized prevention of HNSCC,” they concluded.