Etiology, Epidemiology and Pathophysiology of Oral Squamous Cell Carcinoma: A Review Article

Oral squamous cell carcinoma (OSCC) is the most common malignancy of the oral cavity. It accounts for more than 90% of oral cancers and is ranked as the sixth most prevalent cancer when considered on a global scale. In terms of pathogenesis, genetic, epigenetic, and environmental factors play a role in their interaction. Well-established risk factors are smoked tobacco, alcohol drinking, betel quid chewing, and high-risk human papillomavirus (HPV) infection- especially HPV-16. From these exposures mutate key oncogenes and tumor suppressor genes such as RAS, MYC, and TP53 plus promoter hypermethylation of genes like p16 and DAPK.These molecular changes lead to unrestrained cell proliferation apoptosis inhibition angiogenesis and tissue invasion facilitated by matrix metalloproteinases (MMPs). Geographically, OSCC varies a lot. The cultural practice of chewing betel quid in South and Southeast Asia makes this region the highest implac6tion for this disease, while lower rates are seen in Arab countries as alcohol consumption is not prevalent. In Iraq, increasing tobacco consumption, more waterpipe (shisha) smoking, and lifestyle changes have driven an upward trend of OSCC incidence. It usually affects men above the age of 40; however, recent data show increasing incidence among the younger nonsmokers which may indicate a shift in etiology where HPV infection plays a bigger role. Genetic studies in global and Iraqi populations have shown consistent overexpression of p53, cyclin D1, and EGFR. Conserved molecular pathways because of regional exposure differences. The survival rate remains poor due to late-stage diagnosis and recurrences. To improve patient outcomes in the face of these challenges will require culturally sensitive public health campaigns, early detection facilitated by molecular biomarkers, and targeted therapies that genetic profiling guides. This review synthesizes available evidence on the etiology and epidemiology of OSCC, highlighting gaps in knowledge and proposing avenues for research that can help direct preventive efforts while decreasing this disease’s burden globally.