Using CircuLating Tumor DNA to Risk Adapt Post-Operative Therapy for HPV-associated Oropharyngeal Cancer

Inclusion Criteria: * 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. * For patients with pT0 tumors (unknown primary), there must be at least one metastatic lymph node present in cervical level II. * p16 is strongly positive by immunohistochemistry or high-risk HPV is detected by in-situ hybridization. * Have undergone or will undergo gross total resection of all known disease in the head and neck via transoral robotic surgery. For patients with clinical unknown primary tumors, a patient must undergo both ipsilateral tonsillectomy and base of tongue resection unless the primary is identified clinically or pathologically at the time of surgery. If the primary is identified, then only resection of the primary site is required. If the primary tumor is resected with negative margins with a non-robotic surgery, such as a diagnostic tonsillectomy, this is considered acceptable and further robotic surgery is not necessary. * Have undergone or will undergo neck dissection. * Have at least one of the following after surgery: * Pathologic stage T3 * 2 or more positive lymph nodes * At least one lymph node \>3cm * Contralateral lymph node …