The researchers are doing this study to find out if a personalized approach to chemoradiation therapy (which may include a lower dose of radiation) is as effective as the standard chemoradiation therapy in people with HPV-positive throat cancer. Other purposes of this study include looking at the following:
* Whether a lower dose of radiation in combination with standard chemotherapy causes fewer side effects than the standard dose of radiation therapy in combination with standard chemotherapy * How the study approaches (lower dose of radiation therapy + standard chemotherapy and standard dose of radiation therapy + standard chemotherapy) affect participants' quality of life. The researchers will measure quality of life by having participants fill out questionnaires.
Pathologically (histologically or cytologically) proven diagnosis of HPV associated squamous cell carcinoma of the oropharynx (tonsil, base of tongue, or oropharyngeal walls) or squamous cell carcinoma with an unknown primary. Surgical removal of primary site is allowed.
Patients must test positive for both p16 expression (70% nuclear and cytoplasm expression; Ventana Medical Systems) and mRNA HPV in situ hybridization (RNAscope® 2.5 HD Reagent kit (Advanced Cell Diagnostics, Inc, Hayward, CA). Any CLIA certified testing method can be used.
Clinical stage Tx-2, N1-2c (AJCC, 7th ed.) without evidence of distant metastasis based on FDG PET/CT.
ECOG Performance Status of 0-1 or KPS >/=70
Patients with prior head and neck radiation therapy where there is >30% overlap with the current head and neck radiation fields. Exceptions can be made if determined by the PI/Co-PI that the patient can proceed with protocol activities
Patients whose tumors are borderline T4 based on anterior tumor extension to the extrinsic muscles of the tongue
Patients with simultaneous primary cancers outside of the oropharynx
Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for 3 years or if cure rate from treatment at 5 years to be 90% or greater