Faiza Faria, Stephen E Hawes, John Lin, Jeffrey Schouten, Helen Cristina Stankiewicz Karita, Stephen Cherne, Anjali Vasavada, Ruanne V Barnabas, Judith N Wasserheit, Qinghua Feng, Rachel L Winer
{"title":"The role of human papillomavirus (HPV) E6 oncoprotein as a biomarker in anal cancer screening in persons living with HIV.","authors":"Faiza Faria, Stephen E Hawes, John Lin, Jeffrey Schouten, Helen Cristina Stankiewicz Karita, Stephen Cherne, Anjali Vasavada, Ruanne V Barnabas, Judith N Wasserheit, Qinghua Feng, Rachel L Winer","doi":"10.1158/1055-9965.EPI-25-0327","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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).</p><p><strong>Methods: </strong>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).</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>The HPV-16/18 E6 oncoprotein has potential utility as a triage biomarker for identifying and prioritizing lesions at highest risk for progression.</p><p><strong>Impact: </strong>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.</p>","PeriodicalId":520580,"journal":{"name":"Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology","volume":" ","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1158/1055-9965.EPI-25-0327","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
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.
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