Transcriptionally Active Human Papillomavirus in Male Genital Lichen Sclerosus, Penile Intraepithelial Neoplasia, and Penile Squamous Cell Carcinoma

Penile intraepithelial neoplasia (PeIN) and penile squamous cell carcinoma (PeSCC) are both thought to be associated with male genital lichen sclerosus and human papillomavirus (HPV) infection through dichotomous pathways: (i) undifferentiated PeIN and warty/basaloid PeSCC are thought to be HPV rela...

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Main Authors: Georgios Kravvas, Boyu Xie, Aiman Haider, Michael Millar, Hussain M Alnajjar, Alex Freeman, Asif Muneer, Christopher B Bunker, Aamir Ahmed
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:JID Innovations
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Online Access:http://www.sciencedirect.com/science/article/pii/S2667026724000687
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author Georgios Kravvas
Boyu Xie
Aiman Haider
Michael Millar
Hussain M Alnajjar
Alex Freeman
Asif Muneer
Christopher B Bunker
Aamir Ahmed
author_facet Georgios Kravvas
Boyu Xie
Aiman Haider
Michael Millar
Hussain M Alnajjar
Alex Freeman
Asif Muneer
Christopher B Bunker
Aamir Ahmed
author_sort Georgios Kravvas
collection DOAJ
description Penile intraepithelial neoplasia (PeIN) and penile squamous cell carcinoma (PeSCC) are both thought to be associated with male genital lichen sclerosus and human papillomavirus (HPV) infection through dichotomous pathways: (i) undifferentiated PeIN and warty/basaloid PeSCC are thought to be HPV related, whereas (ii) differentiated PeIN and usual PeSCC are considered HPV independent. Tissue arrays were constructed from male genital lichen sclerosus, undifferentiated and differentiated PeIN, usual-type PeSCC, and unaffected tissues. Staining for p16 and for high-risk and low-risk HPV subtypes through RNAscope was performed. The expression of HPV RNA and p16 were quantified, and appropriate statistical comparisons were undertaken. High-risk HPV was prevalent in undifferentiated PeIN (77%) and less so in PeSCC (46%) and was exiguous or absent in all other tissues. LR HPV was only observed in 2 tissue cores. Strong p16 staining exhibited 96.15% sensitivity and 100% specificity for high-risk HPV. Transcriptionally active HPV is unlikely to be implicated in male genital lichen sclerosus and differentiated PeIN, although it is clearly important in undifferentiated PeIN. The high prevalence of high-risk HPV in usual PeSCC challenges the existing paradigm. Strong p16 positivity was a reliable surrogate marker for the detection of transcriptionally active high-risk HPV.
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spelling doaj-art-0bd670d0e09d40d697fe6bc817b2b5a92025-01-11T06:42:10ZengElsevierJID Innovations2667-02672025-01-0151100320Transcriptionally Active Human Papillomavirus in Male Genital Lichen Sclerosus, Penile Intraepithelial Neoplasia, and Penile Squamous Cell CarcinomaGeorgios Kravvas0Boyu Xie1Aiman Haider2Michael Millar3Hussain M Alnajjar4Alex Freeman5Asif Muneer6Christopher B Bunker7Aamir Ahmed8Department of Dermatology, University College London Hospitals NHS Foundation Trust, London, United Kingdom; Correspondence: Georgios Kravvas, Department of Dermatology, University College London Hospitals NHS Foundation Trust, 235 Euston Road, NW1 2BU, London, United Kingdom.Centre for Stem Cell and Regenerative Medicince, King's College London, London, United KingdomDepartment of Histopathology, University College London Hospitals NHS Foundation Trust, London, United KingdomThe Queen's Medical Research Institute, College of Medicine & Veterinary Medicine, University of Edinburg, Edinburgh, United KingdomDepartment of Urology, University College London Hospitals NHS Foundation Trust, London, United KingdomDepartment of Histopathology, University College London Hospitals NHS Foundation Trust, London, United KingdomDepartment of Urology, University College London Hospitals NHS Foundation Trust, London, United KingdomDepartment of Dermatology, University College London Hospitals NHS Foundation Trust, London, United KingdomCentre for Stem Cell and Regenerative Medicince, King's College London, London, United Kingdom; Department of Cell & Developmental Biology, University College London, London, United KingdomPenile intraepithelial neoplasia (PeIN) and penile squamous cell carcinoma (PeSCC) are both thought to be associated with male genital lichen sclerosus and human papillomavirus (HPV) infection through dichotomous pathways: (i) undifferentiated PeIN and warty/basaloid PeSCC are thought to be HPV related, whereas (ii) differentiated PeIN and usual PeSCC are considered HPV independent. Tissue arrays were constructed from male genital lichen sclerosus, undifferentiated and differentiated PeIN, usual-type PeSCC, and unaffected tissues. Staining for p16 and for high-risk and low-risk HPV subtypes through RNAscope was performed. The expression of HPV RNA and p16 were quantified, and appropriate statistical comparisons were undertaken. High-risk HPV was prevalent in undifferentiated PeIN (77%) and less so in PeSCC (46%) and was exiguous or absent in all other tissues. LR HPV was only observed in 2 tissue cores. Strong p16 staining exhibited 96.15% sensitivity and 100% specificity for high-risk HPV. Transcriptionally active HPV is unlikely to be implicated in male genital lichen sclerosus and differentiated PeIN, although it is clearly important in undifferentiated PeIN. The high prevalence of high-risk HPV in usual PeSCC challenges the existing paradigm. Strong p16 positivity was a reliable surrogate marker for the detection of transcriptionally active high-risk HPV.http://www.sciencedirect.com/science/article/pii/S2667026724000687CarcinogenesisHuman papillomavirusMicroscopyRNA biologySquamous cell carcinoma
spellingShingle Georgios Kravvas
Boyu Xie
Aiman Haider
Michael Millar
Hussain M Alnajjar
Alex Freeman
Asif Muneer
Christopher B Bunker
Aamir Ahmed
Transcriptionally Active Human Papillomavirus in Male Genital Lichen Sclerosus, Penile Intraepithelial Neoplasia, and Penile Squamous Cell Carcinoma
JID Innovations
Carcinogenesis
Human papillomavirus
Microscopy
RNA biology
Squamous cell carcinoma
title Transcriptionally Active Human Papillomavirus in Male Genital Lichen Sclerosus, Penile Intraepithelial Neoplasia, and Penile Squamous Cell Carcinoma
title_full Transcriptionally Active Human Papillomavirus in Male Genital Lichen Sclerosus, Penile Intraepithelial Neoplasia, and Penile Squamous Cell Carcinoma
title_fullStr Transcriptionally Active Human Papillomavirus in Male Genital Lichen Sclerosus, Penile Intraepithelial Neoplasia, and Penile Squamous Cell Carcinoma
title_full_unstemmed Transcriptionally Active Human Papillomavirus in Male Genital Lichen Sclerosus, Penile Intraepithelial Neoplasia, and Penile Squamous Cell Carcinoma
title_short Transcriptionally Active Human Papillomavirus in Male Genital Lichen Sclerosus, Penile Intraepithelial Neoplasia, and Penile Squamous Cell Carcinoma
title_sort transcriptionally active human papillomavirus in male genital lichen sclerosus penile intraepithelial neoplasia and penile squamous cell carcinoma
topic Carcinogenesis
Human papillomavirus
Microscopy
RNA biology
Squamous cell carcinoma
url http://www.sciencedirect.com/science/article/pii/S2667026724000687
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