Prior studies have demonstrated that aberrant expression or mutation of SMAD4 significantly influences the advancement of diverse tumors, including hematopoietic malignancies and solid tumors such as acute myeloid leukemia (25), pancreatic cancer (26), hepatocellular carcinoma (27), head and neck carcinoma (28) and CRC (29). This evidence concerns the gene SMAD4 and head and neck carcinoma.