Acetaldehyde-Producing Oral Microorganisms as Emerging Potential Contributors of Upper Aerodigestive Tract Carcinogenesis

This narrative review explores the potential role of the oral microbiota and dysbiosis in upper aerodigestive tract (UADT) carcinogenesis. The localized accumulation of acetaldehyde (ACH) derived from microbial ethanol metabolism has emerged as a notable, modifiable risk factor under investigation. Specific resident microorganisms, including Neisseria subflava, Streptococcus mitis, Rothia spp., and Candida albicans, exhibit alcohol dehydrogenase activity in vitro, combined with a near-complete lack of local detoxification capacity. This biochemical imbalance turns saliva into a potential reservoir for mutagenic metabolites that could theoretically promote DNA damage. However, robust clinical evidence supporting a definitive connection between these in vitro findings and human carcinogenesis remains limited. Current data are largely observational and prone to confounding from lifestyle factors like tobacco and alcohol use. Similarly, emerging concepts regarding endogenous ACH production through carbohydrate fermentation lack strong clinical confirmation. Nevertheless, these findings open promising new avenues for research. The accessibility of the oral cavity positions the microbiota as a compelling candidate for non-invasive biomarker development and targeted preventive strategies. While longitudinal trials are required to establish definitive causality, exploring these microbiome-mediated pathways offers an encouraging framework to enhance future personalized risk assessment in UADT oncology.