Previous studies using large-scale sequencing technologies have clearly demonstrated that HPV+ versus HPV− HNSCs express different sets of transcription factors and cell cycle regulators, and that the differential expression of host mRNAs is a direct consequence of HPV oncogenic activity.5,11,17,18 Furthermore, certain canonical cancer genes (TP53, CDKN2A, PIC3CA, CASP8, NOTCH1, RB1, TP63 and FAT1) are though to be impaired in both subtypes through mutations in HPV− cases, or through direct or indirect interaction with HPV oncogenes in virus-positive cases.16,19. The gene discussed is CDKN2A; the disease is cancer.