Antioxidant Use after Diagnosis of Head and Neck Squamous Cell Carcinoma (HNSCC): A Systematic Review of Application during Radiotherapy and in Second Primary Cancer Prevention

Approximately 5–20% of HNSCC patients experience second primary cancers within the first 5 years of treatment, contributing to high mortality rates. Epidemiological evidence has linked a low dietary intake of antioxidants to an increased risk of cancer, especially squamous cell carcinoma, prompting research into their potential in neoplasm chemoprevention. Cigarette smoking is the primary risk factor for HNSCC, and a diet rich in antioxidants offers protective effects against head and neck cancer. Paradoxically, smokers, who are at the highest risk, tend to consume fewer antioxidant-rich fruits and vegetables. This has led to the hypothesis that integrating antioxidants into the diet could play a role in both primary and secondary prevention for at-risk individuals. Furthermore, some HNSCC patients use antioxidant supplements during chemotherapy or radiotherapy to manage side effects, but their impact on cancer outcomes remains uncertain. This systematic review explores the evidence for the potential use of antioxidants in preventing second primary cancers in HNSCC patients. In conclusion, none of the antioxidants tested so far (α-tocopherol, β-carotene, JP, Isotretinoin, interferon α-2a, vitamin E, retinyl palmitate, N-acetylcysteine) was effective in preventing second primary tumors in HNSCC patients, and they could only be used in reducing the side effects of radiotherapy. Further research is needed to better understand the interplay between antioxidants and cancer outcomes in this context.