Evaluating a Decreased Dose of Radiation Therapy to the Elective Neck for the Treatment of HPV-Related Oropharyngeal Cancer, ENLIGHT Trial

Inclusion Criteria: * Patients must have a histologically confirmed HPV-related OPSCC, confirmed by HPV in-situ hybridization * Patients must not have received prior treatment (i.e., no induction chemotherapy) * Patients must have evaluable disease (per Response Evaluation Criteria in Solid Tumors \[RECIST\] version \[v\]1.1 response criteria) * Patients must be age \>= 18 years * Patients must have American Joint Committee on Cancer (AJCC) 8th edition stage I-II disease, as defined by a T-classification of T1-3, and N-classification of N1-2, without metastases (M0), as defined by physical examination (including nasopharyngolaryngoscopy) and positron emission tomography (PET) * Patient must receive a staging PET scan prior to registration on study * Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 * Patients may be planned to undergo radiation therapy (RT) alone or RT with concurrent chemotherapy, with chemotherapy managed at the discretion of the treating medical oncologist per standard of care * RT is known to be teratogenic to a developing human fetus. For this reason, patients of child-bearing potential (POCBP) must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) from time of informed consent, for the duration of study participation (while actively receiving RT). Should a patient become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. * NOTE: A POCBP is any patient (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: * Has not undergone a hysterectomy or bilateral oophorectomy * Has had menses at any time in the preceding 12 consecutive months (and therefore has not been naturally postmenopausal for \> 12 months) * POCBP must have a negative pregnancy test prior to CT simulation or sign the Department of Radiation Oncology's pregnancy testing declination form * Note: the timing of the pregnancy test/declination form will follow the policy of the Department of Radiology and Oncology, which requires completion of pregnancy testing or signed pregnancy declination prior to CT simulation * Patients must have the ability to understand and the willingness to sign a written informed consent document prior to registration Exclusion Criteria: * Patients with cT4, cN3, or cM1 disease by AJCC 8th edition * Patients who have had prior RT to the head/neck region that would result in overlap of RT fields * Patients who have had prior major surgery to the head/neck region that could disrupt lymphatic flow * Patients who have an uncontrolled intercurrent illness that would interfere with the receipt of RT including, but not limited to any of the following, are not eligible: * Uncontrolled connective tissue disorders (e.g. lupus, scleroderma) given potential for this to interfere with RT * Psychiatric illness/social situations that would limit compliance with study requirements * Any other illness or condition that the treating investigator feels would interfere with study compliance or would compromise the patient's safety or study endpoints