Poor oral hygiene is an established risk factor of oral cancer. The current study investigated the role of oral microbiome in the development of oral cancer by sequencing the microbial 16S ribosomal RNA gene of salivary DNA of 139 oral cancer cases and 151 controls. Three periodontopathogenic (PPG) bacteria were associated with an increased oral cancer risk. Alcohol, betel quid, cigarette and poor oral hygiene were associated with a higher percentage of salivary PPG bacteria. The positive association between alcohol use and the percentage of salivary PPG bacteria was influenced by ALDH2 polymorphism, with a stronger association observed among ALDH2-deficient individuals. There is a significant positive correlation between the percentage of PPG bacteria and the inflammatory cytokine IL1b in the saliva. In conclusion, PPG bacteria may independently increase oral cancer risk. Alcohol, betel quid, and cigarette may increase oral cancer risk partly by increasing PPG bacteria. PPG bacteria may increase oral cancer risk by enhancing the production of inflammatory cytokine IL1b. Improving oral hygiene to reduce PPG bacteria may reduce oral cancer risk.
