Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignancies and has significant
mortality. Its multi-step cumulative features strongly support early management. Cancer chemoprevention has been
accepted as a promising intervention for early management, and has made enormous progresses over the past 30 years due
to the large number of research studies including many randomized clinical trials. Overall, chemoprevention is an appealing
approach for fighting HNSCC because it is generally safe, cost-effective, and widely available. In this review, we
summarize and discuss new findings and evidences from the most recent clinical trials in chemoprevention of HNSCC.
Our literature search is limited only to those trials published within the past 10 years (2001-2011). Based on our review,
the most extensively studied agents/compounds for chemoprevention continue to be retinoids (e.g., 13-cRA). Additional
agents considered include COX inhibitors, Vitamin A and E forms, and green tea and other natural extracts. However, we
found disappointing results in the studies using retinoids, COX inhibitors and vitamin forms, while encouraging outcomes
were found with most natural extracts. Further study is warranted for validation or improvement of treatment efficacy with
current agents and strategies. Future research may include identification of new biomarkers/targets, improvement of
bioavailability or tissue penetration, combinations of different compounds (or development of dual-action agents) to act
on multiple pathways, and specific study of non-smoking related or other untraditional causes.