Cohort B (patients with HPV-negative, platinum-refractory disease) was included in this trial for the following three reasons: (1) to validate the pre-clinical science which suggested that mitomycin-C would be inactive in mutant TP53 disease, (2) patients with HPV-negative, wild-type TP53 disease may have benefited from mitomycin-C, and (3) clinical trials conducted before the discovery of the etiologic link between HPV and cancer showed that mitomycin-C resulted in tumor response rates of 18–21% in patients with RM-HNSCC [14,15,16,17]. This evidence concerns the gene TP53 and head and neck squamous cell carcinoma.