Transdermal Buprenorphine for the Treatment of Radiation-Induced Mucositis Pain in Head and Neck Cancer Patients

Inclusion Criteria: 1. Patients aged 18-80 years. 2. Histologically confirmed malignancies involving the oral cavity, oropharynx, hypopharynx and larynx (including non-squamous cell histologies, salivary gland carcinomas and unknown primary tumors). 3. Undergoing a course of either definitive radiation (dose of at least 50 Gy to the head and neck region) +/-chemotherapy or adjuvant radiation (at least 50 Gy to the head and neck region) +/- chemotherapy (Patients with a history of prior definitive course of radiation will be allowed). 4. Eastern Cooperative Oncology Group (ECOG) Performance status ≤ 2 5. Concurrent enrollment on interventional trial is allowed. 6. English speaking and literate 7. Patients will be allowed to take radiotherapy mix, viscous lidocaine or magic mouthwash like agents that do not contain opioids. Tylenol allowed for fever and mild pain before starting drug regimen. 8. Adequate organ function: Minor dose adjustments for tramadol is required in severe liver and renal impairment so we would only include patients with adequate organ function outlined in below. No dose adjustment for renal or hepatic impairment is required for TD buprenorphine. Some other parameters like hemoglobin, platelets and white blood count (WBC) are required for administration of standard of care chemotherapy like cisplatin along with radiation in treatment of head and neck squamous cell carcinoma (HNSCC). They are not required for administration of buprenorphine or tramadol. 1. total bilirubin \< 2 mg/dL 2. aspartate aminotransferase (AST) / alanine aminotransferase (ALT) \< 5 times institutional upper limit 3. creatinine clearance \> 30 mL/min/1.73 m2 for patients with creatinine levels above institutional normal" 9. Pregnancy: It is known that standard of care treatments of HNSCC radiation therapy and chemotherapy have detrimental effects on human pregnancy or development of the embryo or fetus. Therefore, female patients participating in this study should avoid becoming pregnant, and male patients should avoid impregnating a female partner. Non-sterilized female patients of reproductive age and male patients should use effective methods of contraception through defined periods during and after study treatment as specified below. Female patients must meet one of the following: * Postmenopausal for at least one year before the screening visit, or * Surgically sterile, or * If they are of childbearing potential, agree to practice two effective methods of contraception from the time of signing of the informed consent form through three months after the last dose of study drug, AND * Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, or * Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence \[e.g., calendar, ovulation, symptothermal, post ovulation methods\] and withdrawal are not acceptable contraception methods.) Male patients, even if surgically sterilized (i.e., status post vasectomy), must agree to one of the following: * Practice effective barrier contraception during the entire study treatment period and through 90 days after the last study drug dose, OR * Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, OR * Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence \[e.g., calendar, ovulation, symptothermal, post ovulation methods\] and withdrawal are not acceptable methods of contraception.) 10. Ability to understand a written informed consent document, and the willingness to sign it. 11. Possession of a smart phone (android or apple-based platforms) and ability to operate a smart phone application. Patients who do not have smart phones will be provide wireless devices that have OM pain app installed on them. Exclusion Criteria: 1. Physical exam demonstrating preexisting mucositis. 2. Preexisting oral infection or ongoing toxicity from prior radiotherapy. 3. History of substance abuse, positive urine drug screen in last six months. 4. Patients with multiple distant metastasis (subjects with resectable oligometastasis will be allowed) 5. Current or recent use (within four weeks of screening) of mixed opioid agonists/antagonists or other opioid antagonists. Methadone use within four weeks of screening. 6. History of prolonged QTc\>greater than 450 milliseconds in males and greater than 470 milliseconds in females. 7. Patients on systemic therapy (chemotherapy or immunotherapy) for another cancer subtype. 8. Patients receiving induction chemotherapy prior to or after radiation/chemoradiation like patients with nasopharyngeal carcinoma 9. Patients with history of abdominal surgery within 60 days of registration, acute gastrointestinal conditions like colitis and appendicitis within four weeks of screening. 10. Patients with conditions that may compromise blood-brain barrier permeability. The blood-brain barrier may become leaky in select neurological diseases, such as amyotrophic lateral sclerosis, epilepsy, brain trauma and edema 11. Patients with a history of myocardial infarction ≤ 6 months prior to registration. 12. Patients with h/o significant respiratory depression; acute or severe bronchial asthma; known or suspected gastrointestinal obstruction, including paralytic ileus. 13. History of serious or severe hypersensitivity reaction to buprenorphine or tramadol or any of its excipients. 14. Patients on anti-depressant and anti-psychotic therapy 15. Pregnant and lactating women are excluded from this study because chemotherapy and radiation given for treatment of HNSCC has a potential for teratogenic or abortifacient effects. Additionally, Buprenorphine is classified as category C for use during pregnancy, which means that the risk of adverse effects on the fetus cannot be ruled out. Buprenorphine does cross the placenta, and the use of opioids during pregnancy may result in neonatal withdrawals soon after birth. Symptoms of this may include irritability, apnea, increased tone, tremor, convulsions, or respiratory depression in the neonate. The onset of withdrawal in a neonate whose mother has taken buprenorphine during the pregnancy could be anywhere from the first day of life to the eighth day of life. 16. Patients with history of seizure disorder as oral tramadol may reduce seizure threshold.