Marshall R. Posner, MD, The Tisch Cancer Institute, New York, NY, discusses current and potential prognostic factors for patients with human papillomavirus (HPV)-positive oropharyngeal cancer. Current research in biomarkers and HPV genotypes may predict patient outcomes more accurately. HPV69 is a rare subtype of HPV but is associated with a worse patient prognosis. Tobacco smoking additionally can affect patient prognostics, with smokers more likely to be excluded from de-escalation trials. Prof. Posner also discusses surgery in treating HPV-positive oropharyngeal cancer, which has the potential to reduce the need for radiotherapy, shown in the SIRS (NCT02072148) and E3311 (NCT01898494) trials. This interview took place at the American Society of Clinical Oncology (ASCO) 2021 Virtual Meeting.