SEER (Surveillance Epidemiology and End Results) data demonstrates a decline in oral cancer for tobacco related sites; however, there is a strong trend toward an increase in human papillomavirus (HPV) implicated sites. Due to the affinity of the virus for lymphoid tissues and posterior placement, today’s dental professional needs to be keenly aware of the subtle symptoms that accompany this newer profile. How does this affect our methods of screening for oral and oropharyngeal cancer, and is the clinical oral examination predictive of histologic diagnosis at an early stage? Two-thirds of oral squamous cell carcinomas are discovered at an advanced stage with five-year survival rates impeded significantly; 83.3% when the disease is discovered in stage I or II, and only 38% when the cancer has metastasized. This presents a call to action to elevate our knowledge regarding examination of high-risk areas and explore adjunctive screening methods to complement the traditional white light examination.