Promoter hypermethylation of K1F1A and EDNRB genes, detected in saliva DNA, is preferentially methylated in salivary rinses from HNSCC compared with healthy patients. In addition, patients with OSCC had higher methylation on the K1F1A promoter. KIF1A and EDNRB are potential biomarkers for HNSCC detection, with K1F1A being more specific for OSCC. This evidence concerns the gene KIF1A and head and neck squamous cell carcinoma.