Cancer
The Role of HPV E6 oncoprotein as a biomarker in anal cancer screening in persons living with HIV Faiza Faria* Faiza Faria Stephen E. Hawes John Lin Jeffrey Schouten Helen C. Stankiewicz Karita Stephen L. Cherne Anjali Vasavada Ruanne V. Barnabas Judith Wasserheit Qinghua Feng Rachel L. Winer
Persons living with human immunodeficiency virus (PLWH) are at elevated risk for anal cancer compared with the general population. Human papillomavirus (HPV) types 16 and 18 cause most anal cancers; E6 oncoprotein expression plays a key role in anal carcinogenesis. We evaluated the performance of HPV 16/18 E6 oncoprotein for detecting anal high-grade squamous intraepithelial lesions (HSIL) in 125 specimens from 82 PLWH undergoing screening, high-resolution anoscopy (HRA) or treatment in Seattle, Washington (2015-2016). Demographic and clinical data, anal cancer screening, diagnosis, and treatment results, were collected from medical records. Anal brush samples were tested for type-specific high-risk HPV (hrHPV) DNA. Samples positive for HPV 16/18 (n=48) were tested for E6 oncoprotein. We described performance of HPV16/18 E6 oncoprotein, HPV16/18 DNA and any hrHPV DNA as biomarkers for HSIL detection (n=49). We calculated prevalence ratios (PR) for associations between these biomarkers and HSIL using a generalized linear model with a Poisson family and robust variance adjusted for CD4 count, HIV viral load, and age. HPV 16/18 E6 (n=3) was more specific but less sensitive than HPV16/18 DNA and any hrHPV DNA. HPV 16/18 E6+ showed 100% specificity, 100% positive predictive value and an adjusted PR of 6.23 (95% CI: 1.12, 34.50) for HSIL compared to hrHPV negative samples; but low sensitivity (6.1%) and moderate negative predictive value (62.3%). We evaluated HSIL disease extent data from HRA impression and found that 50% of four HSILs with >75% disease extent had E6+ samples, whereas none of 30 HSILs with <25% disease extent had E6+ samples. Results demonstrate that HPV 16/18 E6 oncoprotein is highly specific for identifying HSIL and may be useful for prioritizing lesions at the highest risk for cancer. Longitudinal studies may establish E6 oncoprotein’s role in early detection and prevention of anal cancer, either on its own or in combination with other biomarkers.