Compared with HPV-negative HNSCC, HPV-positive HNSCC is characterised by a simpler genomic mutational load, since p53 and Rb are silenced by the viral oncoproteins E6 and E7, but have frequent activating mutations of genes involved in phosphoinositide 3-kinase (PI3K) pathway (reviewed in21,22). The gene discussed is TP53; the disease is head and neck squamous cell carcinoma.