Rather than defining tumors through a global analysis of gene expression, this study took a targeted approach by comparing HNSCC samples based on the presence or absence of HPV and focused specifically on gene expression and mutational patterns in the Rb-E2F/p53 pathways, which are disrupted by the E7 and E6 oncoproteins from HPV. Here, TP53 is linked to head and neck squamous cell carcinoma.