Head and neck cancer (HNC), a complex and aggressive group of malignancies that affect the larynx, oropharynx, hypopharynx, nasopharynx, paranasal sinuses, oral cavity, and salivary glands, is the sixth most prevalent cancer globally. In 2018, it was responsible for 890,000 new cases and led to 450,000 fatalities (Bray et al., 2018, Ferlay et al., 2019). The number of HNC cases is on an upward trend and is expected to increase by 30 % (resulting in 1.08 million new cases annually) by the year 2030 (Bray et al., 2018, Ferlay et al., 2019). Squamous cell carcinomas make up about 90 % of all NHCs (Bhat, Hyole, & Li, 2021). These cancers pose a significant challenge in terms of treatment due to their heterogeneity and genetic complexity (Anderson et al., 2021). Patients with oral lichen planus, oral lichenoid lesions, and oral lichenoid reactions have an elevated risk of developing oral cancers .

The primary risk factors for HNC are tobacco consumption, excessive alcohol intake, and exposure to oncogenic viruses such as human papillomavirus and Epstein-Barr virus (Argiris et al., 2008, Auguste et al., 2020, Mody et al., 2021). Recent research has identified several polymorphisms and biomarkers that are linked to the risk of HNCs (Garajei et al., 2023, Garajei et al., 2022, Mohammadi et al., 2022, Mohammadi et al., 2021, Ramezani et al., 2021, Ramezani et al., 2021). Recent analyses have consistently found across both genders that the intensity of alcohol consumption is the primary alcohol-related factor influencing the risk of HNCs, whereas, the duration of alcohol consumption has a modest effect when the intensity of alcohol consumption is constant (Di Credico et al., 2020). Alcohol consumption becomes a significant risk factor for HNCs when combined with tobacco use, contributing to 75 % of oral cancers (Marziliano, Teckie, & Diefenbach, 2020).

Alcohol dehydrogenases (ADHs) are a set of enzymes found in many organisms. They play a crucial role in the conversion process between alcohols and aldehydes or ketones, which involves the reduction of nicotinamide adenine dinucleotide (NAD+) to NADH (An, Nie, & Xu, 2019). These enzymes are particularly recognized for their function in the oxidation and removal of ethanol (Di, Balesano, Jordan, & Shi, 2021). ADHs are cytosolic enzymes that are predominantly located in the liver, but they can also be found in other tissues such as the gastrointestinal tract and adipose tissue (Di et al., 2021, Gyaneshwari et al., 2024). There are several ADH enzymes, each encoded by a different gene. Some of these genes have multiple variants, and the enzymes produced by these variants can vary in their efficiency at metabolizing ethanol (Edenberg, 2007).

Based on our knowledge in English literature, there were just four meta-analyses (Chang et al., 2012, Chuang et al., 2011, Tan and Ning, 2019, Zhang et al., 2015) reporting the association between ADH1B rs1229984 polymorphisms and the risk of oral cancer with different results and fewer studies compared the present meta-analysis. Herein, we aimed to evaluate the association between ADH polymorphisms including ADH1B rs1229984, ADH7 rs1573496, ADH7 rs1154460, and ADH7 rs284787 and susceptibility to HNCs, as well as finding effective factors in the association with more studies and adding other analyses such as trial sequential analysis (TSA), and outlier analysis, meta-regression analysis, and network analysis for increasing the power and accuracy of data.