INTRODUCTION: Head and neck cancer is one of the most common malignancy in the world. While it has been associated with several factors like alcohol consumption and smoking, there is approximately 25% of head and neck cancer that can be attributed to Human Papillomavirus (HPV) especially HPV 16. HPV associated cancer has been associated with a better prognosis as compared to HPV negative cancers. It has also been shown in previous studies that HPV-negative African Americans have a higher mortality rate as compared to HPV associated cancers in European Americans and HPV-negative European Americans patients. The three states of HPV associated cancers have been compared, which included HPV active, HPV inactive and HPV negative. AIM: The study aims include: 1) Compare the differences in the gene expression profiles of HPV negative HNSCC in AA from EA patients, and determine the differences in their biological make up. 2) Explore and compare the genetic expression profiles of HPV-active, HPV-inactive and HPV-negative head and neck cancer patients. METHODS: A secondary data analysis was conducted on 36 oropharyngeal cancer tissues samples with different HPV status (HPV-active, HPV-inactive and HPV- negative). ANOVA was conducted in R to compare all the three groups from each other and identify the genes that were differentially expressed. Bayes Moderated paired t-test was used to compare two groups of HPV-negative European Americans with HPV-negative African Americans. RESULTS: Our analysis revealed that the genes that were differentially expressed in HPV- active and HPV-negative analysis were different from HPV-active and HPV-inactive analysis. Our analysis also identified genes that were differentially expressed in African Americans as compared to European Americans. DISCUSSION: This study provides the genetic expression profiles in different groups (European Americans and African Americans) based on different HPV stages. Despite the small sample size of our data, we were able to identify the genes that were differentially expressed amongst different conditions in patients who had oropharyngeal carcinoma. We were also able to identify the genes involved in HPV-negative oral cancer comparing the African Americans to the European Americans.