Study of Mucosal Sparing Adjuvant Radiotherapy After Surgical Exploration in HPV+ Head and Neck Cancer of Unknown Primaries

Inclusion Criteria: * Patients meet criteria for intensity-modulated proton therapy (IMPT) treatment for oropharyngeal cancer * If IMPT is declined by patient's insurance, they can be treated with standard of care IMRT using the same applicable standard of care procedures outlined in the procedures manual * Meet criteria for adjuvant chemotherapy (if applicable) * Histological confirmation of human papillomavirus (HPV)+ squamous cell carcinoma as defined by neck node pathology. HPV positivity will be defined as positive staining for p16 and HPV deoxyribonucleic acid (DNA) in situ hybridization (ISH). (If discordant, ribonucleic acid \[RNA\] ISH will be run for confirmatory testing) * Clinical stage T0 N1-N3 and confirmed pathologic stage T0 N1-N2 M0 (American Joint Committee on Cancer \[AJCC\] 8th edition) with one of the following risk factors: * Lymph node \>= 3 cm * \>= 2 positive lymph nodes * Presence of extracapsular extension * \> 1 nodal level involved * Absence of distant metastases on standard diagnostic workup, prior to registration (chest computed tomography \[CT\], chest x-ray \[CXR\], or positron emission tomography \[PET\]/CT) * Able to undergo pre-operative Q-clear series PET/CT head/neck for diagnostic workup of occult primary and nodal disease * Able to undergo transoral surgery and neck dissection by their ears, nose, and throat (ENT) oncologist * Surgical exploration/sampling of all mucosal sites including ipsilateral wide field tonsillecto…