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.