Ari Rosenberg, MD, University of Chicago Medicine, Chicago, IL, discusses the key unanswered questions in head and neck cancer. Many patients with recurrent metastatic head and neck cancer respond well to immuno/immuno-chemotherapy, however, the development of immuno/immuno-chemotherapy resistance in tumors presents a significant challenge, therefore it is vital that new therapies be developed to circumvent this issue. Furthermore, several studies looking at incorporating immunotherapy into the frontline setting have produced negative results, such as the PembroRad trial (NCT02707588), hence a pressing question is how to translate the success of immunotherapy in improving survival in the recurrent metastatic setting into improving outcomes in the curative setting? This interview took place at the American Society of Clinical Oncology (ASCO) 2021 Virtual Meeting.