The top fifteen genes significantly hypomethylated in their promoters in HNSCC compared to potentially premalignant oral lesions are: ART4, EPB41L3, ESRRG, ENPP1, GNG7, PAPSS2, NGEF, HIPK4, GPR158, GSG1L, SMPD3, GDF2, RERE, CDH13, and HS3ST4 (Table 2). This evidence concerns the gene PAPSS2 and head and neck squamous cell carcinoma.