Background: The success of smoking cessation programs is inarguable and has saved thousands of lives by decreasing the incidence of deadly malignancies, including head and neck cancer. Meanwhile, we are witnessing an increasing incidence of human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC), especially in a population of older Caucasian males. Approval and use of immune checkpoint inhibitors (ICI), such as pembrolizumab, have resulted in improved outcomes in patients with HPV-induced OPSCC. It is successfully used in the treatment of recurrent and metastatic disease with meaningful improvements in overall survival. However, concurrent chemoradiotherapy (CCRT) remains the conventional first-line treatment of locally advanced disease in eligible patients and is associated with substantial morbidity.

Case Description: A 78 year-old male patient presented with epistaxis and dysphagia and was diagnosed with locally advanced HPV-positive OPSCC. He was a candidate for CCRT, but refused it and was successfully treated with single agent pembrolizumab. Patient did not experience any adverse reactions. He was using non-prescription cannabis oil during the course of therapy with ICI. Pembrolizumab was discontinued after 2.5 years of therapy as the patient’s cancer remained in remission. Patient was then observed off therapy and did not have recurrent disease.

Conclusions: To our knowledge, this is the first case of cure achieved by single agent ICI in a patient with locally advanced HPV-positive OPSCC who was a candidate for CCRT. In addition, our case adds to the limited literature on the impact of cannabis on patients who are treated with ICI and highlights the importance of further research in understanding the interaction of cannabis with immunotherapy.