Over 40,000 people will be diagnosed with oral cancer this year and over 8,000 people will die from this disease. Men suffer from oral cancer at a rate four times greater than women. The incidence and mortality rate for African American/black (AA/B) and white women in the U.S. is fairly similar. AA/B and white males also have a similar disease incidence; however, AA/B males die at a rate 3-4 times that of their white counterparts. Socioeconomic status resulting in limited access to healthcare for the poor has played a large role in that disparity, with more AA/B men being diagnosed with metastatic disease which is linked to poor prognosis. Historically a disease of tobacco and/or alcohol abuse, oral cancer was declining as a result of decreases in smoking but the decline slowed around the year 2000 when a new cause, with increasing incidence, was identified. That new oral cancer agent was the human papilloma virus (HPV). It has now been suggested that white males are more likely than AA/B males to have HPV-positive oral cancer, a form of the disease that responds better to therapy, and this is driving the disparity in mortality. Studies actually quantifying HPV in tumors of AA/B males are few and more work needs to be done to confirm that that is the case. More recent reports suggest that AA/B and white males have similar incidence of HPV-positive oral cancer, but the progression of the disease is different in AA/B individuals. In this study, we will ask and answer the following questions: 1) do AA/B and white males from underserved populations have similar amounts of HPV+ oral cancer, 2) are the HPV subtypes the same in these two groups and, 3) is the progression of HPV-associated cellular and molecular changes the same for AA/B and white individuals and could late stage at diagnosis be a result of differing disease progression rather than delayed diagnosis? The answers to these questions will be analyzed along with other variables that are associated with prognosis, such as age at diagnosis, stage at diagnosis, tumor grade, a history of risk factors such as alcohol and tobacco abuse, therapy prescribed, completion of therapy and response to therapy. This comprehensive assessment will lend incredible insight into the reasons for the high death rate for AA/B men and will result in future research that will depend upon the outcomes of this work. This could include education and outreach towards the prevention of HPV infection and the development of new therapies specific for HPV- positive oral cancer. This work is important because oral cancer is a painful and destructive disease with poor outcomes for all and disproportionately so for AA/B males. The disparity in mortality cannot be adequately addressed until the factors contributing to it are identified.