Here we test the hypothesis that specific candidate gene methylation markers (CCNA1, NDN, CD1A, DCC, GADD45a, and p16) are associated with tumor recurrence and survival, in a well-characterized, prospective cohort of HNSCC patients with extensive epidemiologic, clinical and outcome information, who were treated by a single group of clinicians with a homogenous treatment approach. This evidence concerns the gene GADD45A and head and neck squamous cell carcinoma.