Abstract
Oxidative stress serves as both a driver and result of redox metabolism across diverse physiological and pathological states, including cancer. Head and neck squamous cell carcinoma (HNSCC), the sixth most prevalent malignancy worldwide, is no exception. HNSCC is strongly linked to modifiable external risk factors such as tobacco smoking, alcohol consumption, and high-risk human papilloma (HR-HPV) infection. These risk factors are associated with elevated oxidative stress, which contributes to carcinogenesis through DNA damage, chronic inflammation, and dysregulation of cell signaling pathways. Current treatment options for HNSCC have limitations and burden of side effects. Studies have been conducted on potent dietary antioxidants for the prevention and adjunctive treatment of HNSCC. This review aims to explore the contribution of oxidative stress to carcinogenesis in general and the three major risk factors for HNSCC. We evaluate latest evidence for nine dietary antioxidants such as vitamin C, vitamin E, carotenoids, epigallocatechin-3-gallate (EGCG), and curcumin, that have shown promise in preclinical and clinical studies. We discuss how these compounds mitigate ROS, influence cancer-related signaling pathways, and modulate tumor microenvironment. Despite encouraging findings, current clinical data remain limited and inconclusive, highlighting the need for further research on possible dietary antioxidants for HNSCC.