As MHC-II-dependent antigen presentation is critical for CD4+ help in CD8+ T-cell responses, which are essential for the control and clearance of cancerous cells, it is likely that the expression of non-self-derived viral antigens or tumor derived neoantigens, combined with intact MHC-II presentation and appropriate co-stimulation contributes to the markedly better patient outcomes for HPV+ versus HPV− head and neck carcinomas. This evidence concerns the gene CD8A and head and neck carcinoma.