To understand the underlying mechanisms of differences in patterns of tumor-specific hypermethylation, we have analyzed the aberrant promoter methylation profile of HNSCC using seven important tumor-related pathway genes, including DAPK, RASSF1 (apoptosis pathway), BRCA1, MLH1 (DNA repair pathway), p16 (cell-cycle pathway), ECAD (cell-cell adhesion), GSTP1 (Xenobiotic pathway) and three methylated loci (MINT1, MINT2 and MINT31) in the high cancer incidence zone of Northeast India. Here, DAPK1 is linked to head and neck squamous cell carcinoma.