Head and Neck Cancer Prevention by Phytochemicals: Current Status and Challenges

Cancer is a growing health concern worldwide associated with a rise in life expectancy, lifestyle, and environmental exposures. In India, head and neck squamous cell carcinomas (HNSCC) are most common cancers in males and sixth most common cancers worldwide. HNSCC are causally associated with use of tobacco, areca nut, consumption of alcohol, and human papilloma virus (HPV) infection. Primary prevention by minimizing exposure to known carcinogens is promising, but limited success is achieved due to addiction, economic, and individual freedom-related issues. Advancements in treatments of HNSCC have not improved 5-year survival rate beyond 50% in the last two decades. HNSCC development is a multifactorial, multistep process encompassing modifiable initiation, promotion, and progression events. Several plant-derived phytochemicals prevent/delay the onset and decrease incidence and/or multiplicity of carcinogen-induced tumors in HNSCC experimental models. Experimentally proven chemopreventive agents were tested in clinical trials, and only a few of them showed promising results. Important issues for disparity of results between preclinical studies and clinical trials are failure to mimic human conditions in animal models with respect to carcinogen exposure complexities, tissue(s) systems, exposure of normal vs. damaged tissue/DNA to potential chemopreventive agents, bioavailability, toxicity, and mechanistic aspects. This review discusses the progress of phytochemical(s)-mediated chemoprevention in preclinical settings along with completed clinical trials of HNSCC and suggestions for effectively addressing issues related to mismatch. Combining phytochemical(s)-mediated chemoprevention with primary prevention strategies and/or current treatment strategies may provide a better outcome.