Shortened Course of Radiation Therapy After Trans-oral Robotic Surgery in Patients With HPV-Mediated Oropharyngeal Squamous Cell Carcinoma.

Step 1 Registration: Pre-Operative Eligibility Inclusion Criteria: * Participant aged ≥ 18 years. * Diagnosis of oropharyngeal squamous cell carcinoma. * Eligible to receive transoral robotic surgery. * If status is known, p16 positivity or HPV positivity by in situ hybridization on pathological sampling of lymph node or primary oropharyngeal tumor. If status not known at the time of step-1 registration, otherwise eligible participants may be enrolled and HPV/p16 status must be determined prior to step-2 registration. * Pre-operative TTMV-HPV DNA test collected or is planned to be collected. Pre-operative TTMV-HPV DNA may be collected anytime up until the day of surgery as long as it is prior to surgery. * Standard of care tests completed within 60 days of registration may be used for screening. * Tests results are not required to confirm eligibility for step 1 registration. * ECOG Performance Status ≤ 2 * Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines. Exclusion Criteria: * History of prior mucosal head and neck cancer treated with radiation therapy * Prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of this study * Participant has smoked cigarettes within 1 month of registration * Prior systemic anti-cancer therapy or any investigational therapy ≤ 14 days or within five half-lives prior to startin…