The Role of Human Papillomavirus E6 Oncoprotein as a Biomarker in Anal Cancer Screening in Persons Living with HIV

BACKGROUND: Molecular biomarkers could enhance anal cancer screening accuracy in people living with human immunodeficiency virus. We assessed the performance of human papillomavirus (HPV) 16/18 E6 oncoprotein in detecting anal high-grade squamous intraepithelial lesions (HSIL) in men living with human immunodeficiency virus. METHODS: We analyzed clinical data from 125 clinic visits of 82 men living with human immunodeficiency virus who underwent high-resolution anoscopy in Seattle, Washington (2015-2016), including the presence and extent of HSIL. Anal brush specimens were tested for high-risk HPV DNA, with HPV-16/18-positive samples further tested for E6 oncoprotein. Sensitivity, specificity, positive predictive value, and negative predictive value of HPV-16/18 E6 oncoprotein for HSIL were calculated, along with prevalence ratios with 95% confidence intervals. RESULTS: Forty-eight (38.4%) samples were HPV-16/18 positive, including three E6 positive. Forty-nine (39.2%) samples had corresponding HSIL. Specificity and positive predictive value of HPV-16/18 E6 for HSIL was 100%, and the prevalence ratio was 7.33 (95% confidence interval, 2.44-22.07) for HPV-16/18 E6-positive versus high-risk HPV-negative samples. Sensitivity for HSIL, however, was only 6.1%, with a moderate negative predictive value (62.3%). Two of four persons with HSILs with >75% disease extent had corresponding HPV-16/18 E6-positive samples, whereas none of 30 persons with <25% extent did. CONCLUSIONS: The HPV-16/18 E6 oncoprotein has potential utility as a triage biomarker for identifying and prioritizing lesions at the highest risk for progression. IMPACT: People living with human immunodeficiency virus are at an increased risk of anal cancer and would benefit from improved screening methods. Further research may elucidate the role of HPV-16/18 E6 oncoprotein in anal cancer prevention, alone or combined with other biomarkers.