To determine if DNA methylation or histone acetylation accounts for the reduced PKD1 gene expression in HNSCC, head and neck cancer cells were treated with DNA methyltransferase inhibitor, 5-aza-2′-deoxycytidine (5-aza-dC), and/or histone deacetylase HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) and trichostatin A (TSA), and levels of PKD1 gene and protein expression was examined. This evidence concerns the gene HDAC9 and head and neck squamous cell carcinoma.