Based on the findings that CXXC4, DACT2, HHIP, ZIC1, and ZIC4 are methylated in HNSCC cell lines and that their methylation is not present in normal oral and tracheal epithelium, we further investigated the frequency of methylation of these genes in laryngeal and oral tumor samples and matched surgical margin samples of OSCC patients. Here, ZIC1 is linked to head and neck squamous cell carcinoma.