Interestingly, in a recent prospective nonrandomized longitudinal study on 279 patients with OPSCC, Seikaly et al. showed that primary surgery offered the best survival outcomes, in comparison with definitive RT with or without CT, in smokers with p16-positive OPSCC and in patients with p16-negative cancers, whereas there was no survival advantage in non-smokers with p16-positive tumors [84]. The gene discussed is CDKN2A; the disease is cancer.