Head and neck squamous cell carcinoma (HNSCC) continues to be a significant cause of cancer worldwide. Tobacco and alcohol use are the most common risk factors for HNSCC. Over the past five years, research has identified the human papillomavirus (HPV) as a factor in the development of approximately 25 percent of HNSCC. Current research at the Sanford Cancer Research Center shows that the immune system can recognize HPV induced cellular changes, making HPV+ cancer more curable then HPV- cancer. Clinical trials are being developed that will improve cancer therapy by selectively treating sub-types of HNSCC through immunotherapy. The role of the primary care physician in the care of head and neck cancer is in the identification, referral and follow-up of these affected patients. The risk factors and signs and symptoms of head and neck cancer are discussed as well as indications for referral to a head and neck oncologist.