Translational aspects of the modern genetics in head and neck cancers FRANCESCO PADUANO 1,2, *;EMANUELA ALTOMARE 2,3 ;BENEDETTA MARRELLI 1 ;VINCENZO DATTILO 4 ; HAIZAL MOHD HUSSAINI 5 ;PAUL ROY COOPER 5 ;MARCO TATULLO 6 1 Marrelli Health-Tecnologica Research Institute, Biomedical Section, Stem Cells and Medical Genetics Units, Crotone, 88900, Italy 2 University “Magna Graecia” of Catanzaro, Catanzaro, 88600, Italy 3 Fondazione “Massimo Marrelli”, Crotone, 88900, Italy 4 Genetics Unit, IRCCS Centro San Giovanni di Dio Fatebenefratelli, Brescia, 20125, Italy 5 Sir John Walsh Research Institute, Faculty of Dentistry, University of Otago, Dunedin, 9054, New Zealand 6 Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari Aldo Moro, Bari, 70124, Italy Key words: Genome-wide association studies (GWAS), Oral cancer (OC), Oral squamous cell carcinoma (OSCC), OSCC of the head and neck (SCCHN), Oral and pharyngeal cancer (OPC) Abstract: Oral Cancer (OC) is one of the most recurrent cancers in the head and neck squamous cancer (SCCHN) category. Recently, the genome-wide association studies (GWAS) have gained growing interest in the scientific community. GWAS have identified several pathways involved in the interactions among general risk factors and genomic variants affecting SCCHN. This systematic overview aims to critically evaluate the latest data reported within the scientific literature. The aim was to investigate the impact of genetic aspects on SCCHN onset and prognosis, involving other clinical and systemic co-factors. PubMed, Google Scholar, and Cancer Genetics Web databases have been systematically investigated for original articles published in the last two years, reporting studies on the main queries addressed in this work. This review also comparatively describes the impact of environmental and pathological co-factors in different types of cancers, clarifying and updating the role of genetic factors in SCCHN onset and development. The main outcomes reported may be helpful to drive clinicians towards their clinical evaluations for the most appropriate therapeutic approach in SCCHN. Introduction Many genetic and environmental factors play specific role in increasing the risk of developing cancer. Nevertheless, not all people who are exposed to carcinogens or who have other risk factors will develop cancer. In fact, there are numerous pathways that work in the early stages, before the clinical onset. It is well known that genetics has a strong impact on several human diseases; however, several other factors influence the risk in developing oral cancers: tobacco smoke contains carcinogens that substantially increase the risk of developing cancer of the mouth. Furthermore, foods and other substances introduced with the diet can increase the risk of oral cancer: alcohol consumption is correlated with a higher risk of developing head and neck cancer (Huber and Tantiwongkosi, 2014; Kumar et al., 2016; Siegel et al., 2016). Cancers that develop in the oral cavity encompass multiple anatomic sites, including the tongue, the gums, the lips, the mouth floor, hard palate, and retromolar trigone. Cancer of the oropharyngeal space located between the hyoid bone and the soft palate includes the tonsillar region, base of the tongue, soft palate and uvula and the posterior and lateral pharyngeal walls. All of these sites are considered at risk of developing OSCC of the head and neck (SCCHN) (Huber and Tantiwongkosi, 2014). Although oral cancer (OC) and oral and oropharyngeal cancer (OPC) possess different behaviour and prognosis, both of them are characterised by atypical squamous epithelial cells, and are termed oral squamous cells carcinoma (OSCC) (Kumar et al., 2016; Siegel et al., 2016). The worldwide incidence of OC increases with age and depends on the patient’s gender; it has been determined that the average age for OC diagnosis is 64 years old, while 95 percent of OC diagnoses occur after 40 years (Mignogna et al., 2004; Abram et al., 2012; Bray et al., 2018). More than 600,000 new oral cavity cancer cases have been estimated to occur each year, and the majority of cases are typically recorded in south-central Asian countries (Conway et al., 2018). *Address correspondence to: Francesco Paduano, francesco.paduano@tecnologicasrl.com Received: 24 November 2021; Accepted: 22 December 2021 BIOCELL ech T Press Science 2022 Doi: 10.32604/biocell.2022.020462 www.techscience.com/journal/biocell This work is licensed under a Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Published Online: 17 February 2022