In contrast to most HNSCC, HPV-positive tumours are more likely to have wild-type TP53. Human papillomavirus-infected cells accomplish G1 to S-phase transition through the targeted degradation of pRb by the viral E7 oncoprotein and consequently, CDKN2A/p16 is overexpressed. Here, CDKN2A is linked to head and neck squamous cell carcinoma.