The p53 protein is a transcription factor and tumor suppressor protein encoded by TP53. Loss of p53 function occurs in more than 90% of HNSCC through loss of heterozygosity, interaction with HPV viral oncoprotein E6 or increased expression of MDM2 (seen in about 5% of HNSCC and promotes rapid degradation of p53 protein) [37, 69]. Here, MDM2 is linked to head and neck squamous cell carcinoma.