Trial of De-Intensified Post-operative Chemoradiation Following Robotic Surgery for HPV-positive Oropharyngeal Cancer

This study will enroll patients with HPV-associated oropharyngeal cancer, undergoing resection of all gross visible disease at the primary site and in the lymph nodes. A total of 40 patients who have had or will require surgery to remove cancer cells prior to starting chemoradiation may be enrolled. All eligible patients will receive de-intensified cisplatin-based chemoradiation, with high-risk patients receiving a higher dose and longer treatment period than other patients on the study. The study will assess whether a de-intensified version of standard chemoradiation treatment will be just as effective in treating HPV-associated oropharyngeal cancer while causing less side effects than standard dosing.

Inclusion Criteria: 1. AJCC 8th edition T0-3N0-2 p16-positive oropharyngeal (tonsil, base of tongue, glossotonsillar sulcus, soft palate, oropharyngeal wall) squamous cell carcinoma or squamous cell carcinoma of unknown primary involving the cervical lymph nodes. Cytologic diagnosis from a cervical lymph node is sufficient for diagnosis in the presence of clinical evidence of a primary tumor in the oropharynx. 2. For patients with pT0 tumors (unknown primary), there must be at least one metastatic lymph node present in cervical level II. 3. p16 should be strongly and diffusely positive in the nuclear and cytoplasmic component in greater than 70% of the tumor cells. 4. Have undergone or will undergo gross total resection of all known disease in the head and neck via transoral robotic surgery. For patients with unknown primary tumors, a minimum of an ipsilateral tonsillectomy and base of tongue resection is required. 5. Have undergone or will undergo neck dissection. 6. Have at least one of the following after surgery: * Pathologic stage T3 * 2 or more positive lymph nodes * At least one lymph node \>3cm * Lymphovascular invasion * Perineural invasion * Extranodal extension * Close/positive margins: Close margins are considered \