p16 overexpression is a standard surrogate biomarker for high-risk HPV-associated OPSCC.23,46,47 But notably, p16 overexpression is also present in a number of non-HPV-driven tumours probably related to RAS and BRAF mutations48 although not in KRAS.49 Other head and neck carcinomas have proven to be HPV–/p16+ likely related to misconfigurations in the p16–Rb–cyclin-D1 pathway inducing cell cycle activation in HPV-negative carcinomas.50 The gene discussed is RB1; the disease is carcinoma.