Celecoxib Through Surgery and Radiation Therapy for the Treatment of Advanced Head and Neck Cancer

Inclusion Criteria:

* Male or female subject aged ≥ 18 years.
* Advanced-stage (overall stage III and IV) head and neck cancers (sinonasal oral cavity, oropharynx, larynx, and hypopharynx) undergoing surgical resection and then adjuvant radiation. Primary and recurrence cases are acceptable
* Karnofsky performance status of \>= 70
* Hemoglobin \>= 10 g/dL
* Total bilirubin =\< 2 mg/dL
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional upper limit of normal (ULN)
* Albumin \> 3.5 g/dL
* Estimated glomerular filtration rate (eGFR) \>= 30 mL/min/1.73 m\^2 or creatinine clearance \>= 30 mL/min by Cockcroft-Gault
* Serum potassium within normal limits
* Negative serum or urine pregnancy test at screening for women of childbearing potential
* Highly effective contraception for female subjects throughout the study and for at least 5 days after the last dose of study therapy if the risk of conception exists
* Recovery to baseline or =\< grade 1 Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy
* Willing to maintain a diary of all opioids used during the trial for the treatment of pain
* Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines
* Subject has verbally confirmed they are willing to complete adjuvant radiation therapy if recommended after surgery per protocol.
* Adjuvant radiation has been recommended by the institutional treatment planning conference with the best available data, but will be confirmed based on final surgical pathology.

Exclusion Criteria:

* Known distant metastatic disease or the tumor is deemed not surgically resectable
* Established in a pain management clinic or has taken opioids regularly \>= 6 months
* Known or suspected to be poor CYP2C9 metabolizers based on previous history/experience with other CYP2C9 substrates (such as warfarin, phenytoin)
* Known hypersensitivity to celecoxib, aspirin, other non-steroidal anti-inflammatory drug (NSAID)s, or sulfonamides
* Uncontrolled hypertension defined as blood pressure (BP) \> 150 mmHg systolic or \> 90 mmHg diastolic on three consecutive reads, taken in one sitting despite optimal antihypertensive treatment
* Patients with a known history of the following:

  * Cerebrovascular accident (CVA), stroke, or cardiovascular thrombotic events (e.g. acute myocardial infarction).
  * Chronic heart failure.
  * Gastrointestinal bleeding, ulceration, peptic ulcer disease, or perforation of the stomach or intestines.
  * Aspirin-sensitive asthma.
  * Chronic kidney disease, stage 4 or 5
* Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen
* The subject has uncontrolled, significant intercurrent or recent illness requiring systemic therapy, would preclude safe study participation, or is deemed clinically significant by the investigator
* Known human immunodeficiency virus (HIV) infection with a detectable viral load within 6 months of the anticipated start of treatment.

  * Note: Patients on effective anti-retroviral therapy with an undetectable viral load within 6 months of the anticipated start of treatment are eligible for this trial
* Known chronic hepatitis B virus (HBV) or hepatitis C virus infection with a detectable viral load.

  * Note: Patients with an undetectable HBV viral load on appropriate suppressive therapy are eligible. Patients with an undetectable hepatitis C virus (HCV) viral load on appropriate treatment are eligible
* Subjects taking prohibited medications . A washout period of prohibited medications for a period of at least 5 half-lives or as clinically indicated should occur prior to the start of treatment