Ari Rosenberg, MD, University of Chicago Medical Center, Chicago, IL, discusses promising new strategies for treatment de-intensification for head and neck cancer. These strategies are typically focused on patients with human papillomavirus (HPV) -associated head and neck cancer who have a favorable prognosis. Possible de-intensification strategies include replacing cytotoxic chemotherapy with targeted therapies including rituximab, de-intensifying adjuvant treatment after minimally-invasive surgery, and response-adapted de-intensification. This interview took place at the European Society for Medical Oncology (ESMO) 2021 congress.