De-escalation of Adjuvant Radiation for Low-Risk HPV Oropharyngeal Cancers

Inclusion Criteria: * Patients must be ≥ 18 years of age on the day of signing informed consent. * Patients must have a diagnosis of p16+ and/or HPV+ squamous cell carcinoma of the oropharynx (including base of tongue, glossotonsilar sulcus, tonsil, soft palate, vallecula, and/or posterior oropharyngeal wall). * pathologic stage T1-2 N1 M0 (AJCC 8th ed.) stage I or T3 N0-1 M0 stage II (AJCC 8th ed.) SCCA of the oropharynx, with ≤ 5 distinct nodes involved with tumor, ≤ 2mm ECE (extracapsular extension), ≥ 2mm surgical margins at primary site. * Karnofsky Performance Status (KPS) ≥ 60 within 8 weeks prior to registration. * neutrophil:lymphocyte ratio ≤ 5 within 8 weeks of registration. * hemoglobin count ≥ 10 within 8 weeks of registration. The patient may receive transfusion to reach this goal. * current non-smoker (at least 6 months) with ≤ 15 pack-year smoking history * start radiation within 8 weeks of resection (6 weeks preferable) * have undergone resection of the primary site with Transoral Surgery and neck dissection of at least the ipsilateral neck * Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. * Ability to understand and willingness to sign a written informed consent. Exclusion Criteria: * Perineural invasion at primary site * Lymphovascular space invasion at primary site * Level 4 nodal involvement (even if resected) * Retropharyngeal nodal involvement (even if resected) * any intact, unresected disease * nodal disease pathologically invading adjacent neck musculature * Patients treated via an invasive, non-oral approach to the primary site, including jaw-splitting mandibulotomy with resection or lateral pharyngotomy * Prior history of malignancy diagnosed within 2 years prior to registration, except for nonmelanomatous skin cancer that has completed treatment and the patient is deemed as being disease-free or Gleason 6 prostate cancer that is undergoing active surveillance. * Patient with extracapsular extension (ECE) who has not had a biopsy of an ipsilateral neck lymph node that demonstrated squamous cell carcinoma