While direct interactions between HPV-specific ABCs and CD4+ TILs, which have been scarcely studied regarding their antigen specificity in HPV+ HNSCC [131,133], are likely to occur in the TME, direct interactions between HPV-specific B cells and CD8+ T cells are, despite similar antigen reactivity patterns [11,78], unlikely as dendritic cells (DCs) and not B cells are in general considered the major cell type capable of antigen cross-presentation [151]. This evidence concerns the gene CD4 and head and neck squamous cell carcinoma.