Interim Digital PET/CT in Predicting Outcomes for Participants With Locally Advanced Oropharyngeal Cancer Undergoing Chemoradiation Therapy

Inclusion Criteria:

* Patient who will undergo definitive radiation with concurrent chemotherapy with weekly (preferred) or high dose cisplatin for histologically confirmed locally advanced squamous cell carcinoma of the oropharyngeal carcinoma
* Patient must have clinically or radiographically evident measurable disease at the primary site and at nodal station(s). Tonsillectomy or local excision of the primary or nodal disease is not permitted
* P16 and/or human papillomavirus (HPV) status obtained on biopsy specimen
* Low risk classification:

  * HPV positive, T1-3, N1-2b, M0 with =\< 10 pack years smoking history
  * Note: Twenty cigarettes is considered equivalent to one pack.
  * Number of pack years = (number \[No.\] of cigarettes per day x number of years of smoking)/20 OR
  * Intermediate risk classification:

    * HPV positive, T4, N3, M0 and/or HPV positive with \> 10 pack year smoking history
    * HPV negative, T1-3, N1-2b, M0, with =\< 10 pack years smoking history OR
  * High risk classification: HPV negative, T4, N3, M0 and/or HPV negative with \> 10 pack year smoking history
* Patients with no contraindications to PET imaging or cisplatin as stated in the section Exclusion Criteria
* No prior history of radiation therapy
* Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Patients with remaining teeth will have undergo a dental evaluation prior to enrollment
* Ability to provide informed consent obtained prior to participation in the study and any related procedures being performed
* Women of child-bearing potential (WOCBP) must have a negative pregnancy test within 14 days of the first administration of study treatment. Urine human chorionic gonadotropin (HCG) is an acceptable pregnancy assessment.

Exclusion Criteria:

* Prior cancers except non-melanoma skin cancer outside of the head and neck unless disease free for 5 years
* Carcinoma of unknown primary, even if p16 positive
* Clinical or radiologic evidence of metastatic disease as defined by disease below the clavicles
* Simultaneous primary cancers or separate bilateral primary tumor sites with the exception of patients with bilateral tonsil cancers
* Subjects who are breast-feeding, or have a positive pregnancy test will be excluded from the study. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
* Medical contraindications to PET imaging (e.g. pregnancy, nursing mothers, weight greater than 420 pounds)
* Medical contraindications to cisplatin or prior allergic reaction to cisplatin
* Subjects who are unable to receive intravenous contrast due to a contrast allergy or poor renal function
* Subjects who are prisoners
* Any serious and/or unstable pre-existing medical disorder (aside from malignancy exception above), psychiatric disorder, or other conditions that could interfere with subject?s safety, obtaining informed consent or compliance to the study procedures, in the opinion of the investigator. This could include severe, active co-morbidities such as:

  * Uncontrolled cardiac disease (hypertension, unstable angina, myocardial infarction within last 6 months, uncontrolled congestive heart failure, cardiomyopathy with decreased ejection fraction)
  * Uncontrolled diabetes
  * Acute bacterial or fungal infection requiring intravenous antibiotics at time of registration
  * Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days of registration