Intensity-Modulated Radiation Therapy in Treating Patients with HPV-Positive Oropharyngeal Cancer

Inclusion Criteria

• Pathologically (histologically or cytologically) proven diagnosis of squamous cell carcinoma of the oropharynx, which include the sites tonsil, base of tongue, soft palate, or posterior oropharyngeal wall; histologic variants will be included (papillary squamous cell carcinoma and basaloid squamous cell carcinoma); cytologic diagnosis from a cervical lymph node is sufficient in the presence of clinical evidence of a primary tumor in the oropharynx
• Patients must have detectable HPV circulating tumor deoxyribonucleic acid (ctDNA) Score Report at Screening or have a detectable baseline HPV ctDNA Score Report (Naveris test) if no primary site is biopsied
• If the primary side is biopsied: Patient's tissue must be positive for p16 by immunohistochemical staining (> 70% staining) of the primary site. Fine needle aspiration (FNA) biopsy specimens of nodes may be used as the sole diagnostic tissue if formalin-fixed paraffin-embedded cell block material is not available for p16 immunohistochemistry
• Clinical stage T1-T3, N1-N2b (American Joint Committee on Cancer [AJCC] 7th edition) with no distant metastases based on the following diagnostic workup
• General history and physical examination within 8 weeks prior to registration
• Fiber optic exam with laryngopharyngoscopy (mirror and/or fiber optic and/or direct procedure) within 8 weeks prior to registration
• One of the following combinations of imaging is required within 8 weeks of registration: * CT scan of the neck (with contrast) and a positron emission tomography (PET)/CT of neck and chest (with or without contrast) * Or a magnetic resonance imagining (MRI) of the neck (with contrast) and a PET/CT of neck and chest (with or without contrast) * Note: A CT scan of the neck and/or a PET/CT performed for the purposes of radiation planning may serve as both staging and planning tools
• Patients must provide their personal smoking history prior to registration; patients cannot have a cumulative personal smoking history that exceeds 10 pack-years * Number of pack-years = (frequency of smoking [number of cigarettes per day] x duration of cigarette smoking [years]) / 20 * Note: Twenty cigarettes is considered equivalent to one pack; cigar and pipe tobacco consumption is not included in calculating lifetime pack-years
• Zubrod performance status of 0-1 within 8 weeks prior to registration
• Age >= 18
• Absolute neutrophil count (ANC) >= 1,500 cells/mm^3 (within 2 weeks prior to registration)
• Platelets >= 100,000 cells/mm^3 (within 2 weeks prior to registration)
• Hemoglobin >= 8.0 g/dl (within 2 weeks prior to registration); Note: the use of transfusion or other intervention to achieve hemoglobin (Hgb) >= 8.0 g/dl is acceptable
• Serum creatinine =< 1.5 mg/dl or creatinine clearance (CC) >= 50 ml/min determined by 24 hour collection or estimated by Cockcroft-Gault formula (within 2 weeks prior to registration)
• Negative serum pregnancy test within 14 days prior to registration for women of childbearing potential
• Patients who are human immunodeficiency virus (HIV) positive but who have no prior acquired immunodeficiency syndrome (AIDS)-defining illness and have CD4 cells of at least 350/mm^3 are eligible; HIV-positive patients must not have multi-drug resistant HIV infection or other concurrent AIDS-defining conditions; patients must not be sero-positive for hepatitis B (hepatitis B surface antigen positive or anti-hepatitis B core antigen positive) or sero-positive for hepatitis C (anti-hepatitis C antibody positive); however, patients who are immune to hepatitis B (anti-hepatitis B surface antibody positive) are eligible (e.g. patients immunized against hepatitis B)
• The patient must provide study-specific informed consent prior to study entry
• Must have detectable screening plasma HPV deoxyribonucleic acid (DNA) (also referred to as circulating tumor [ct]HPV DNA)

Exclusion Criteria

• Cancers considered to be from an oral cavity site (oral tongue, floor of mouth, alveolar ridge, buccal or lip), or the nasopharynx, hypopharynx, or larynx, even if p16 positive
• Carcinoma of the neck of unknown primary site origin (even if p16 positive)
• Distant metastasis or adenopathy below the clavicles
• Gross total excision of both primary and nodal disease; this includes tonsillectomy, local excision of primary site, and nodal excision that removes all clinically and radiographically evident disease
• Simultaneous primary cancers or separate bilateral primary tumor sites
• Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 1095 days (3 years) (for example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible)
• Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowable
• Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
• Severe, active co-morbidity defined as follows: * Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months * Transmural myocardial infarction within the last 6 months * Acute bacterial or fungal infection intravenous antibiotics at the time of registration * Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days of registration * Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol other than those listed * Acquired immune deficiency syndrome (AIDS); note, however, that HIV testing is not required for entry into this protocol; protocol-specific requirements may also exclude immune-compromised patients
• Pregnancy
• Prior allergic reaction to cisplatin
• Normal MRI exclusion criteria will apply; a standard MRI safety form will be used to identify potential conditions warranting exclusion
• Electrical implants such as cardiac pacemakers or perfusion pumps
• Ferromagnetic implants such as aneurysm clips, surgical clips, prostheses, artificial heart, valves with steel parts, metal fragments, shrapnel, bullets, tattoos near the eye, or steel implants
• Ferromagnetic objects such as jewelry or metal clips in clothing
• Claustrophobia
• History of seizures
• Patients with glomerular filtration rate (GFR) < 15 ml/min/1.73 m^2 or who are on dialysis will not have dynamic contrast-enhanced (DCE)-MRI scan; these patients will have conventional anatomical MRI without contrast
• Missing or undetectable baseline plasma HPV DNA level