HNC sensitivity to genotoxic agents is a function of multiple discrete biological events, such as activation of pathways associated with the human papillomavirus (HPV) or mutation of tumor suppressors such as TP53. Unfortunately, we and others have shown that individual patient responses are not completely uniform across patient groups (e.g., HPV-associated vs. HPV-independent, wildtype vs. mutant TP53), and this may be due in large part to the heterogenous activation of acquired resistance pathways once treatment starts (3, 4, 10, 122–127). Here, TP53 is linked to neoplasm.