Oral squamous cell carcinomas are a major cause of morbidity and mortality, and tobacco usage, alcohol consumption, and poor
oral hygiene are established risk factors. To date, no large-scale case-control studies have considered the effects of these risk factors on the composition of the oral microbiome, nor microbial community associations with
oral cancer. We compared the composition, diversity, and function of the oral microbiomes of 121
oral cancer patients to 242 age- and gender-matched controls using a metagenomic multivariate analysis pipeline. Significant shifts in composition and function of the oral microbiome were observed with poor
oral hygiene, tobacco smoking, and
oral cancer. Specifically, we observed dramatically altered community composition and function after
tooth loss, with smaller alterations in current tobacco smokers, increased production of
antioxidants in individuals with
periodontitis, and significantly decreased
glutamate metabolism
metal transport in
oral cancer patients. Although the alterations in the oral microbiome of
oral cancer patients were significant, they were of substantially lower effect size relative to microbiome shifts after
tooth loss. Alterations following
tooth loss, itself a major risk factor for
oral cancer, are likely a result of severe ecological disruption due to habitat loss but may also contribute to the development of the disease.