Gain of PMAIP1 (18q21.31) solely or in conjunction with gain of PTPN1 (20q13.13), detected in saliva DNA, differentiated 100% of HNSCC cases from normal controls with high sensitivity and specificity, with no tumor site differentiation. However, it has clinical utility for non-invasive HNSCC diagnosis and screening, including OSCC. This evidence concerns the gene PMAIP1 and head and neck squamous cell carcinoma.