We examined racial disparities among 102 oropharyngeal carcinoma (OPC) patients (30 African Americans and 72 whites) comparing rates of transcriptionally active human papillomavirus (HPV)16/18 and p16INK4a overexpression, with times to disease progression and disease-specific survival (DSS). Expression of HPV16/18 transcripts was assessed by reverse transcription and polymerase chain reaction using type-specific E6/E7 primers; p16 INK4a was evaluated by immunohistochemistry. African Americans were significantly more likely to present with high T stage disease and receive nonsurgical treatment. HPV16/18 was present in 63% of patients; no racial differences were observed. Silenced p16INK4a in OPC was significantly more common in African Americans (15/24) than in whites (20/69) (P =.004) and in HPV16+ African Americans (6/24) than in HPV+ whites (2/42) (P =.023). Kaplan-Meier analysis for DSS revealed a protective effect for p16 INK4a overexpression (P =.0028; hazard ratio [HR], 0.23), HPV16+ (P =.036; HR, 0.38), and whites (P =.0039; HR, 0.27). Shorter DSS was associated with primary definitive chemoradiation (P =.019; HR, 3.49) and T3/T4 disease (P =.0001; HR, 7.75). A protective effect with respect to disease progression was observed for HPV16+ (P =.007; HR, 0.27), whites (P =.0006; HR, 0.197), and p16INK4a overexpression (P =.0001; HR, 0.116). African Americans with OPC experience poorer outcomes likely due to p16INK4a silencing, higher T stage, and nonsurgical treatment but not lower rates of transcriptionally active HPV16/18. © 2014 Elsevier Inc. All rights reserved.