Among HPV-associated cancers, the predominant substitutions occurring are activating mutations of PIK3CA, inactivating mutations of TRAF3 or CYLD, and amplification of FGFR3 and the cell cycle gene E2F. Among HPV-unrelated cancers, inactivating substitutions in the tumor suppressor genes TP53 and CDKN2A are predominant [17, 21, 22]. The gene discussed is CYLD; the disease is cancer.