Digital PET Scan for the Prediction of Outcomes in Patients With Locally Advanced Oropharyngeal Cancer

Inclusion Criteria:

* Patient who will undergo definitive radiation with concurrent chemotherapy with cisplatin 40 mg/m\^2 weekly (preferred) or high dose cisplatin 100 mg/m\^2 for histologically confirmed locally advanced squamous cell carcinoma of the oropharynx
* 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 (archival or fresh)
* Patients must provide their personal smoking history prior to registration
* Patients must fall into one of the following stage (American Joint Committee on Cancer \[AJCC\] 8) and risk groups based on pre-treatment work-up and smoking history:

  * Low risk classification:

    * p16 and/or HPV positive, T1-3, N1-2, M0 with =\< 10 pack years smoking history OR
  * Intermediate risk classification:

    * p16 and/or 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:

    * p16 and/or HPV negative, T4, N3, M0
    * p16 and/or HPV negative with \> 10 pack year smoking history
* Patients with no contraindications to PET imaging or cisplatin
* No prior history of radiation therapy
* Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Patients with remaining teeth must undergo a dental evaluation prior to enrolment
* 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
* Women of child-bearing potential and men who are sexually active should be willing and able to use medically acceptable forms of contraception throughout the treatment phase of the trial and until 60 days following the last study treatment

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