Chemoprevention of squamous cell carcinoma of the head and neck: no time to lose momentum.

The prospects for chemoprevention to reduce the incidence of squamous cell carcinoma of the head and neck (SCCHN) are great. The tissue at risk for harboring disease is relatively accessible for examination and biopsy. Patients appropriate for study can be easily identified by their risk factors and the presence of premalignant lesions. Our understanding of the pathogenesis of SCCHN is ever increasing, and offers new opportunities to explore strategies for prevention therapies. In this issue of Cancer Prevention Research, Saba and colleagues report on a phase Ib trial of celecoxib plus erlotinib to prevent progression to higher-grade dysplasia or invasive carcinoma in patients with oral premalignant lesions. The overall response rate was 57%, though by the time of last analysis, 85% of patients relapsed. In this commentary, challenges to the success of chemoprevention clinical trials for SCCHN, such as pitfalls in using surrogate biomarkers and reversal of histologic premalignant changes as study endpoints, are discussed. In addition, strategies to help ensure further development in the field of head and neck cancer prevention are reviewed. These include focusing efforts on tobacco cessation and human papillomavirus vaccination, targeting key molecular drivers of head and neck carcinogenesis, and focusing on combination strategies that have the potential to eradicate premalignant clones, even if some toxicity is encountered.