One of the earliest observational reports in the head and neck cancer literature was by Skinner et al. who found that patients with oral cavity, oropharynx (HPV status not reported), larynx and hypopharynx cancer on metformin at the time of radiation had a lower locoregional recurrence rate compared to controls matched for tumor and nodal stage, surgical margin status, and TP53 status (p = 0.04) [7]. This evidence concerns the gene TP53 and head and neck cancer.