To determine the expression profile of methyltransferases and demethylases in HNSCC tumorigenesis, we performed an expression analysis of the DNA methyltransferases DNMT1, DNMT3A, and DNMT3B, the DNA demethylases TET1, TET2, TET3, and TDG, and the RNA methyltransferase TRDMT1 from the perspective of lymph node metastasis, invasion, and HPV16 infection in HNSCC patients. This evidence concerns the gene DNMT3A and head and neck squamous cell carcinoma.