CDKN2A/p16 opposes cyclin D1 function by negatively regulating RB1 phosphorylartion and a genetic (loss of heterozygosity (LOH)) or epigenetic (promoter methylation) alteration in this gene is frequently observed, resulting in a lack of p16 expression in most HNSCC (Weber et al, 2003). This evidence concerns the gene RB1 and head and neck squamous cell carcinoma.