De-Escalated Adjuvant and Definitive Radiation Therapy Informed by DART 2.0 ctHPV-DNA

Inclusion Criteria: * PRE-REGISTRATION (optional): Provide written informed consent * Age \>= 18 years * Histological confirmation of squamous cell carcinoma originating from or suspected to be originating from the oropharynx * Plan for gross total surgical resection via trans oral surgery with curative intent and at least unilateral neck dissection OR chemoradiotherapy with cisplatin. Note: The patient must be cisplatin eligible even if an alternate is used due to drug shortage * Absence of distant metastases on standard diagnostic work-up =\< 16 weeks prior to registration. (Chest CT or PET/CT) * Eastern Cooperative Oncology Group (ECOG) performance status (PS) =\< 1 * Negative pregnancy test done =\< 7 days prior to registration, for women of childbearing potential only * Ability to complete questionnaire(s) by themselves or with assistance * Provide written informed consent * Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study) * Willing to provide blood samples for correlative research purposes, including anonymous shipment of samples to for NavDx testing Exclusion Criteria: * Any of the following: * Pregnant women * Nursing women * Men or women of childbearing potential who are unwilling to employ adequate contraception * Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere sign…