Oral cancers (OC) are cancers that arise in several regions within the oral cavity such as the lips, gums, tongue, lining of the cheeks, and the floor or roof of the mouth. Approximately 400,000 cases were diagnosed worldwide in 2020, with almost 50% of these resulting in the death of the patient. Despite efforts to improve diagnostic and therapeutic methods available, most OC is detected at a late stage and the mortality rate remains high. The five-year survival rate for individuals diagnosed with OC is 68.5%, according to data from 2013-2019 from the National Cancer Institute. OC can be preceded by premalignant disorders of the oral cavity, including oral leukoplakia, which is categorised by the degree of dysplasia and transformation rates. Epithelial dysplasia can be indicative of an early neoplastic process, with severe or high-grade dysplasia having a higher chance of malignant transformation and worse overall prognosis. Due to the late diagnosis of most OC and the dense lymphatic network found in the oral cavity, metastasis is very common. Cervical lymph node metastasis is the prognostic factor most associated with morbidity and poor patient outcomes for OC.

The most important aetiological factors in the development of OC are alcohol and tobacco consumption, and more recently there has been increasing interest in the oral microbiome and its role in OC development. The exact mechanisms by which alcohol consumption influences oral carcinogenesis remain unclear, but it has been postulated to act via multiple pathways including direct DNA damage, inflammation, carcinogenic metabolites, acting as a co-carcinogen, altering hormone regulation and metabolic reprogramming of oral cells and tumours. When alcohol enters the body, it is metabolised by alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) enzymes. The ALDH enzymes have important roles as cancer stem cell (CSC) markers in several types of cancers, including OC, as well as contributing to tumour growth, metastasis, and therapeutic resistance. Additionally, there is evidence in other cancers of bacteria having a direct causal relationship with carcinogenesis. However, no distinct relationship between the oral microbiome and OC has been defined. Exogenous factors, such as alcohol consumption, can alter the composition of the microbiome, increase host susceptibility to oral dysbiosis, as well as affect immune responses of the oral cavity. Therefore, the overall aim of this research was to investigate the multiple pathways by which alcohol consumption promotes malignant transformation and progression of OC, using oral cell lines, in vitro ethanol exposure and commensal oral microbiota as a model of these processes.