This is a non-randomized, open-label phase II clinical trial that studies the effect of reduced dose radiation therapy and chemotherapy after surgery in treating patients with human papillomavirus (HPV) caused throat cancer. Giving reduced dose radiation therapy and chemotherapy after surgery may improve quality of life compared with standard of care primary chemoradiation approach without compromising survival.

PRIMARY OBJECTIVE:

I. To measure swallowing function and disease specific quality of life of patients with oropharyngeal cancer treated with transoral surgery and reduced intensity adjuvant therapy.

SECONDARY OBJECTIVES:

I. To examine kinetics of circulating tumor deoxyribonucleic acid (DNA) in patients treated with transoral surgery.

II. To estimate local control, progression free and overall survival using transoral surgery and reduced intensity adjuvant therapy.

OUTLINE: Based on pathologic findings after standard of care transoral surgery, patients are assigned to 1 of 3 groups.

GROUP I (LOW RISK): Patients whose small tumor was removed completely and have only one lymph node involved will undergo clinical observation.

GROUP II (MEDIUM RISK): Patients whose tumor was removed completely but has certain features that make it more likely to come back such as growth around the nerves or into the vessels, or has more than one lymph nodes involved, will undergo external body radiation therapy (EBRT) for 5 weeks in the absence of disease progression or unacceptable toxicity.

GROUP III (HIGH RISK): Patients whose tumor has a "positive margin", which means the tumor could not be removed with healthy tissue around it or tumor grows significantly outside the lymph node will undergo EBRT for 6 weeks and receive cisplatin intravenously (IV) weekly for 6 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 3 years.

Inclusion Criteria:

• Histologically proven squamous cell carcinoma of the oropharynx
• Clinical stage T1-2, N0-N3, M0 by American Joint Committee on Cancer (AJCC) 8 criteria
• Must have tumors deemed surgically resectable with acceptable morbidity
• Estimated life expectancy of at least 12 weeks
• Must give informed consent
• Must have Eastern Cooperative Oncology Group (ECOG) performance status =< 3
• Must have detectable circulating HPV DNA levels
• Platelets >= 100,000/ul
• Absolute neutrophil count (ANC) >= 1,500/ul
• Hemoglobin > 8 g/dl (use of transfusion to achieve this is acceptable)
• Total bilirubin < 2 X institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 3 X institutional ULN
• Serum creatinine < 2 x institutional ULN or creatinine clearance > 50 ml/min as determined by 24 hour collection or estimated by Cockcroft-Gault formula
• Negative pregnancy test, if applicable

Exclusion Criteria:

• Patients may not have received previous therapy for their head and neck squamous cell carcinoma (SCC), including chemotherapy, radiation therapy, or surgery beyond biopsy

• Second primary malignancy. Exceptions are:

  • Patient had a second primary malignancy but has been treated and disease free for at least 3 years
  • In situ carcinoma (e.g. in situ carcinoma of the cervix)
  • Non-melanomatous carcinoma of the skin

• Patients with metastatic disease beyond the neck will be excluded

• Serious concomitant systemic disorders (including active infections) that would compromise the safety of the patient or compromise the patient's ability to complete the study, at the discretion of the investigator

• Age < 18 years

• Patients with human immunodeficiency virus (HIV) infection are not automatically excluded, but must meet the following criteria: CD4 count is > 499/cu mm and their viral load is < 50 copies/ml. Use of highly active antiretroviral therapy (HAART) is allowed

• Grade 3-4 electrolyte abnormalities (Common Terminology Criteria for Adverse Events [CTCAE], version [v.] 5)

  • Serum calcium (ionized or adjusted for albumin) < 7 mg/dl (1.75 mmol/L) or > 12.5 mg/dl (> 3.1 mmol/L) despite intervention to normalize levels
  • Magnesium < 0.9 mg/dl (< 0.4 mmol/L) or > 3 mg/dl (> 1.23 mmol/L) despite intervention to normalize levels
  • Potassium < 3.0 mmol/L or > 6 mmol/L despite intervention to normalize levels
  • Sodium < 130 mmol/L or > 155 mmol/L despite intervention to normalize levels

• Women who are pregnant, due to the teratogenic effects of radiation therapy and chemotherapy on the unborn fetus. Women of childbearing age must agree to undergo a pregnancy test prior to therapy and to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and for 6 months after. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately

• Tumor deemed unresectable with acceptable morbidity:

  • Tumors > 4 cm in size (T3 or higher)
  • Tumors of the base of tongue < 4 cm but with deep invasion of tongue musculature placing hypoglossal nerve or both lingual arteries at risk
  • Significant extension into hypopharynx
  • Extension into soft palate beyond 1/3 of the width

• Clinically extensive extranodal extension (ENE) e.g. radiologic evidence of invasion of carotid artery, gross extension into sternocleidomastoid muscle or deep neck muscles.

Lymph nodes larger than 6 cm without clinical ENE will be allowed