A Direct Comparative Analysis of HPV DNA with Single-Molecule RNA and p16INK4a Protein Expression in Lichen Sclerosus: Implications for Diagnostics and Pathogenesis
Introduction: Emerging evidence suggests a relationship between chronic, intermittent, occluded exposure of a susceptible epithelium to urine and male genital lichen sclerosus (MGLSc), although human papillomavirus (HPV) may also play a role. Aims and methods: This study investigated the association...
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Elsevier
2025-07-01
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| Series: | JID Innovations |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667026725000232 |
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| author | Georgios Kravvas Boyu Xie Clarisse Ganier Henk van den Munckhof Ellen van den Munckhof Maurits de Koning Sandra Jerkovic Gulin Alex Freeman Aiman Haider Hussain Alnajjar Asif Muneer Magnus Lynch Michael Millar Aamir Ahmed Christopher Barry Bunker |
| author_facet | Georgios Kravvas Boyu Xie Clarisse Ganier Henk van den Munckhof Ellen van den Munckhof Maurits de Koning Sandra Jerkovic Gulin Alex Freeman Aiman Haider Hussain Alnajjar Asif Muneer Magnus Lynch Michael Millar Aamir Ahmed Christopher Barry Bunker |
| author_sort | Georgios Kravvas |
| collection | DOAJ |
| description | Introduction: Emerging evidence suggests a relationship between chronic, intermittent, occluded exposure of a susceptible epithelium to urine and male genital lichen sclerosus (MGLSc), although human papillomavirus (HPV) may also play a role. Aims and methods: This study investigated the association between MGLSc and HPV across the prepuce. Preputial samples from uncircumcised patients with MGLSc undergoing circumcision were tested for MGLSc distribution, HPV genotyping, RNAscope, and p16INK4a detection. Results: Preputial samples from 9 patients with MGLSc were analyzed, with 9 distinct areas per prepuce, yielding 81 samples. These included MGLSc, non-MGLSc, and indeterminate regions. Various mucosal and beta HPV types were detected, most commonly HPV24, HPV23, HPV36, and HPV9. HPV DNA was found in all patients, and high-risk HPV types were found in 6. No significant differences were observed in total HPV (P = .1) or oncogenic HPV (P = .6) between MGLSc and non-MGLSc tissues. Transcriptionally active HPV was absent in all samples on the basis of independent RNAscope and p16INK4a staining. Discussion: HPV DNA was detected in a mosaic pattern across the prepuce, with no significant differences between MGLSc and non-MGLSc skin. The absence of transcriptional activity suggests that HPV in MGLSc is incidental and may not contribute toward pathogenesis. |
| format | Article |
| id | doaj-art-a417bedf870149f9b875d0e1dade9344 |
| institution | Kabale University |
| issn | 2667-0267 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | JID Innovations |
| spelling | doaj-art-a417bedf870149f9b875d0e1dade93442025-08-20T03:50:21ZengElsevierJID Innovations2667-02672025-07-015410036710.1016/j.xjidi.2025.100367A Direct Comparative Analysis of HPV DNA with Single-Molecule RNA and p16INK4a Protein Expression in Lichen Sclerosus: Implications for Diagnostics and PathogenesisGeorgios Kravvas0Boyu Xie1Clarisse Ganier2Henk van den Munckhof3Ellen van den Munckhof4Maurits de Koning5Sandra Jerkovic Gulin6Alex Freeman7Aiman Haider8Hussain Alnajjar9Asif Muneer10Magnus Lynch11Michael Millar12Aamir Ahmed13Christopher Barry Bunker14Department 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, London NW1 2PG, United Kingdom.Centre of Gene Therapy and Regenerative Medicine, King's College London, London, United Kingdom; Cell and Developmental Biology, University College London, London, United KingdomCentre of Gene Therapy and Regenerative Medicine, King's College London, London, United KingdomCerba Research, Rijswijk, The NetherlandsCerba Research, Rijswijk, The NetherlandsCerba Research, Rijswijk, The NetherlandsDepartment of Dermatology and Venereology, Ryhov County Hospital, Jönköping, Sweden; Division of Cell Biology, Department of Biomedical and Clinical Sciences, The Faculty of Medicine and Health Sciences, Linköping University, Linköping, SwedenDepartment of Histopathology, 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 Urology, University College London Hospitals NHS Foundation Trust, London, United KingdomCentre of Gene Therapy and Regenerative Medicine, King's College London, London, United KingdomQueen’s Medical Research Institute, University of Edinburgh, Edinburgh, United KingdomCentre of Gene Therapy and Regenerative Medicine, King's College London, London, United Kingdom; Cell and Developmental Biology, University College London, London, United KingdomDepartment of Dermatology, University College London Hospitals NHS Foundation Trust, London, United KingdomIntroduction: Emerging evidence suggests a relationship between chronic, intermittent, occluded exposure of a susceptible epithelium to urine and male genital lichen sclerosus (MGLSc), although human papillomavirus (HPV) may also play a role. Aims and methods: This study investigated the association between MGLSc and HPV across the prepuce. Preputial samples from uncircumcised patients with MGLSc undergoing circumcision were tested for MGLSc distribution, HPV genotyping, RNAscope, and p16INK4a detection. Results: Preputial samples from 9 patients with MGLSc were analyzed, with 9 distinct areas per prepuce, yielding 81 samples. These included MGLSc, non-MGLSc, and indeterminate regions. Various mucosal and beta HPV types were detected, most commonly HPV24, HPV23, HPV36, and HPV9. HPV DNA was found in all patients, and high-risk HPV types were found in 6. No significant differences were observed in total HPV (P = .1) or oncogenic HPV (P = .6) between MGLSc and non-MGLSc tissues. Transcriptionally active HPV was absent in all samples on the basis of independent RNAscope and p16INK4a staining. Discussion: HPV DNA was detected in a mosaic pattern across the prepuce, with no significant differences between MGLSc and non-MGLSc skin. The absence of transcriptional activity suggests that HPV in MGLSc is incidental and may not contribute toward pathogenesis.http://www.sciencedirect.com/science/article/pii/S2667026725000232Gene transcriptionInflammatory skin diseasesPapillomavirusRNA biologyTranscription |
| spellingShingle | Georgios Kravvas Boyu Xie Clarisse Ganier Henk van den Munckhof Ellen van den Munckhof Maurits de Koning Sandra Jerkovic Gulin Alex Freeman Aiman Haider Hussain Alnajjar Asif Muneer Magnus Lynch Michael Millar Aamir Ahmed Christopher Barry Bunker A Direct Comparative Analysis of HPV DNA with Single-Molecule RNA and p16INK4a Protein Expression in Lichen Sclerosus: Implications for Diagnostics and Pathogenesis JID Innovations Gene transcription Inflammatory skin diseases Papillomavirus RNA biology Transcription |
| title | A Direct Comparative Analysis of HPV DNA with Single-Molecule RNA and p16INK4a Protein Expression in Lichen Sclerosus: Implications for Diagnostics and Pathogenesis |
| title_full | A Direct Comparative Analysis of HPV DNA with Single-Molecule RNA and p16INK4a Protein Expression in Lichen Sclerosus: Implications for Diagnostics and Pathogenesis |
| title_fullStr | A Direct Comparative Analysis of HPV DNA with Single-Molecule RNA and p16INK4a Protein Expression in Lichen Sclerosus: Implications for Diagnostics and Pathogenesis |
| title_full_unstemmed | A Direct Comparative Analysis of HPV DNA with Single-Molecule RNA and p16INK4a Protein Expression in Lichen Sclerosus: Implications for Diagnostics and Pathogenesis |
| title_short | A Direct Comparative Analysis of HPV DNA with Single-Molecule RNA and p16INK4a Protein Expression in Lichen Sclerosus: Implications for Diagnostics and Pathogenesis |
| title_sort | direct comparative analysis of hpv dna with single molecule rna and p16ink4a protein expression in lichen sclerosus implications for diagnostics and pathogenesis |
| topic | Gene transcription Inflammatory skin diseases Papillomavirus RNA biology Transcription |
| url | http://www.sciencedirect.com/science/article/pii/S2667026725000232 |
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