The differences described between HPV-AOC and its counterpart associated with tobacco and alcohol have recently led to a new classification of p16INK4a-positive HPV-AOC for the eighth edition of the American Joint Committee on Cancer Staging Manual (14), a substantial revision of diagnostic approaches for oropharyngeal cancer, and the launch of several clinical trials of deintensified treatment. The gene discussed is CDKN2A; the disease is oropharynx cancer.