This study is to determine whether a mathematical model can be used to choose a radiation delivery method to improve the rate of a rapid response.

Investigators hypothesize that using individual patient proliferation saturation index (PSI) to select radiotherapy fractionation (conventional fractionation or hyperfractionation) may improve the likelihood of a rapid response (defined as ≥ 32% reduction in volume at 4 weeks).

Inclusion Criteria:

• Stated willingness to comply with all study procedures and availability for the duration of the study
• Male or female, aged ≥ 18 years
• Pathologically (histologically or cytologically) proven diagnosis of p16+ or HPV+ squamous cell carcinoma (including the histological variants papillary squamous cell carcinoma and basaloid squamous cell carcinoma) of the oropharynx; cytologic diagnosis from a cervical lymph node is sufficient in the presence of clinical evidence of a primary tumor in the oropharynx. Clinical evidence should be documented, and may consist of pathology, palpation, imaging, or endoscopic evaluation, and should be sufficient to estimate the size of the primary (for T stage).
• American Joint Committee on Cancer (AJCC) 8th edition staging T1-3 N0-1 MO
• Patients must have clinically or radiographically evident measurable disease at the primary site or at nodal stations.
• CT or MRI performed at least 1 week apart. This can consist of diagnostic imaging and radiation therapy planning imaging.
• No evidence of distant metastases
• Eastern Cooperative Oncology Group Performance Status 0 to 3

Exclusion Criteria:

• Age < 18
• Positive urine pregnancy test
• Evidence of distant metastases
• Gross total excision of both primary and nodal disease; this includes tonsillectomy, local excision of primary site, and nodal excision that remove all clinically and radiographically evident disease
• Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
• Patients with a medical condition or social situation that at the discretion of the PI would preclude them from completion of the trial

Adverse events were collected from date participant signed informed consent to 7 days for non serious or 30 days for serious adverse events after last day of study participation, an average of 1 year.