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A comparison of the detection of biomarkers in infections due to low risk versus high-risk human papillomavirus types
Affiliation:1. The Ohio State University Comprehensive Cancer Center, Columbus, OH, United States of America;2. Phylogeny Medical Laboratory, Powell, OH, United States of America;3. Weill Cornell College of Medicine, New York, NY, United States of America;1. Department of Pathology and Laboratory Medicine, Zucker School of Medicine at Hofstra Northwell, United States of America;2. Biostatistics Unit, Feinstein Institute for Medical Research, Northwell Health, United States of America;1. Institute of Pathology, Spedali Civili Brescia, Italy;2. Gastroenterology and Hepatology Section, Department of Medicine, University of Perugia, Italy;3. Pathology Institute, Azienda Ospedaliera Universitaria, Ospedali Riuniti di Trieste, Trieste, Italy;1. Department of Pathology, University of Pittsburgh Medical Center, A711 Scaife Hall, 3550 Terrace Street, Pittsburgh, PA 15261, USA;2. Department of Radiology, University of Pittsburgh Medical Center, Presbyterian University Hospital Suite E204, 200 Lothrop Street, Pittsburgh, PA 15213, USA;3. Division of Hematopathology, University of Pittsburgh Medical Center, Hill Building, 3rd Floor, 3477 Euler Way, Pittsburgh, PA 15213, USA;1. Pathology section, Rashid hospital, United Arab Emirates;2. ENT department, Dubai hospital, United Arab Emirates;3. General & Plastic surgery unit, Rashid hospital, United Arab Emirates
Abstract:Adjunctive immunohistochemistry tests for human papillomavirus (HPV) infection include p16 and Ki67 as well as the more recently discovered biomarkers importin-β, exportin-5, Mcl1, and PDL1. The purpose of this study was to compare the expression of these biomarkers in HPV infection due to the high-risk types such as HPVs 16, 18, 31, 33, 35, and 51 versus lesions that contain the low risk types HPV 2, 6 or 11. We studied 35 lesions with low risk HPV types (verruca vulgaris = 10 cases, condyloma acuminatum = 15 cases, CIN 1 with HPV 6/11 = 10 cases) and 25 CIN 1 or 2 lesions with a high-risk HPV type. The 25 high-risk positive CIN 1–2 cases had strong expression of the panel p16, Ki67, importin-β, exportin-5, Mcl1, and PDL1 where each protein localized to the cells in the parabasal aspect of the lesion. In comparison, neither p16, importin-β, exportin-5, Mcl1, nor PDL1 were increased in the epithelia of the lesions with the low risk HPV types; Ki67 showed variable expression. HPV viral capsid L1 protein and viral DNA were excellent markers of infection in the lesions with low risk types. Thus, p16, importin-β, exportin-5, Mcl1, and PDL1 are not only biomarkers of high-risk HPV infection but can also differentiate such lesions from those that contain low risk HPV types. Low risk HPV infections can be best differentiated from their mimics by viral L1 capsid detection and/or HPV DNA by in situ hybridization.
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