Swallowing Outcomes and Circulating Tumor DNA in Patients With HPV Related Oropharyngeal Cancer Treated With Transoral Surgery and Reduced Intensity Adjuvant Therapy

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