This phase 1 clinical trial, designed in patients with recurrent HNSCC undergoing salvage surgery to evaluate the safety of combining chronic PDE5 inhibition to reverse tumor-induced immunosuppression, and MUC1/polyICLC immunization to prime a tumor specific immune response, seems to confirm the previous clinical evidence indicating beneficial actions for these two interventions in patients with malignancies. The gene discussed is PDE5A; the disease is cancer.