Since TP53 mutations and HPV infection represent tumor initiating events in HNC [4, 109], p53 inactivation likely represent the initial cause of deregulation of cluster L4 genes, particularly since they were overexpressed in high-grade OPLs, in which TP53 mutations frequently occur and are understood to predispose to malignant transformation [17, 104]. Here, TP53 is linked to neoplasm.