This phase II trial studies how well using circulating tumor deoxyribonucleic acid (DNA) to guide lower dose radiation therapy works in treating patients with human papillomavirus infection (HPV)-associated oropharyngeal cancer. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. Recently, a blood test has been developed to detect the human papillomavirus in the blood and determine how many viral particles are present. Researchers want to compare any good and bad effects of using the lower dose radiation therapy with chemotherapy compared to the usual standard of care dose chemotherapy in patients who clear the human papillomavirus particles from their blood.
Pathologically confirmed diagnosis of squamous cell carcinoma of the oropharynx (unknown primary, base of tongue, tonsil, oropharyngeal walls, soft palate). Cytologic or fine needle aspiration (FNA) confirmation is sufficient if a biopsy of the primary tumor is not feasible
P16 positive immunohistochemical staining. FNA may be used as the sole diagnostic tissue. If staining was done at an outside hospital, central review by the Ohio State University (OSU) department of pathology must occur prior to trial enrollment
Clinical stage T0, N1-N2, T1-2, N1-N2, T3-T4, N0-2 (American Joint Committee on Cancer [AJCC] 8th edition) including no evidence of distant metastases based on general history, imaging, physical examination, and examination with laryngopharyngoscopy
Clinical or radiographic evidence of measurable disease at the primary site or lymph nodes. Simple tonsillectomy or excision of primary without removal of nodal disease is permitted, as is excision of gross nodes but with intact primary site
Recurrent disease
Clinical or radiographic evidence of metastatic disease or adenopathy below the clavicles
Cancers from an oral cavity site, even if p16 positive
Patients with simultaneous primary cancers or separate bilateral primary tumors will be excluded, except for patients with bilateral tonsil cancers