The role of human papillomavirus (HPV) 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 HIV (PLWH). 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 HIV (MLWH).

METHODS

We analyzed clinical data from 125 clinic visits of 82 MLWH who underwent high-resolution anoscopy in Seattle, Washington (2015-2016), including presence and extent of HSIL. Anal brush specimens were tested for high-risk (hr)HPV DNA, with HPV-16/18-positive samples further tested for E6 oncoprotein. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of HPV-16/18 E6 oncoprotein for HSIL were calculated, plus prevalence ratios (PR) with 95% confidence intervals (CIs).

RESULTS

Forty-eight samples (38.4%) were HPV-16/18 positive, including three also E6 positive. Forty-nine (39.2%) had corresponding HSIL. Specificity and PPV of HPV-16/18 E6 for HSIL was 100% and the PR was 7.33 (95%CI:2.44-22.07) for HPV-16/18 E6 positive versus hrHPV-negative samples. Sensitivity for HSIL, however, was only 6.1%, with moderate NPV (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.

CONCLUSION

The HPV-16/18 E6 oncoprotein has potential utility as a triage biomarker for identifying and prioritizing lesions at highest risk for progression.

IMPACT

PLWH are at 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.