Omission of Postoperative Radiation in HPV-Associated Oropharyngeal Cancer Using ctHPVDNA Surveillance (OPERATION)

Inclusion Criteria: * Provision of signed and dated informed consent form. * Stated willingness to comply with all study procedures and availability for the duration of the study. * Male or female, ≥ 18 years of age (no upper age limit). * Biopsy proven squamous cell carcinoma. * p16 positive (diffuse ≥ 70% tumor cell expression, with at least moderate (2/3+ staining intensity). * NavDx positive, HPV16 TTMV only. * AJCC 8th edition cT0-2 N1 M0. * Well lateralized tonsil (\>1 cm from midline, tonsil, base of tongue, glossotonsillar sulcus primary tumors. * ≤ 2 lymph nodes, each ≤ 3cm, -OR- 1 lymph node \>3 but \< 6 cm. * ≤10 pack-years of cigarette smoking or no cigarette smoking for ≥ 5 years (regardless of pack years). * Anatomically (e.g. adequate exposure) and physically amenable to TORS per the judgement of the operating surgeon. * Radiologic confirmation of the absence of hematogenous metastasis within 12 weeks prior to surgery; at a minimum CT imaging of the chest. PET/CT is acceptable. * ECOG Performance Status 0-1. * CBC with differential obtained within 8 weeks prior to surgery, with adequate bone marrow function defined as follows: * Platelets ≥ 100,000 cells/mm3 * Hemoglobin ≥ 9.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb ≥ 9.0 g/dl is acceptable. Transfusion must be completed within 2 to 4 weeks prior to enrollment.) * Adequate renal and hepatic function within 8 weeks prior to surgery, defined as follows: * Serum creatinine …