{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T12:11:47Z","timestamp":1781179907365,"version":"3.54.1"},"reference-count":34,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,5,23]],"date-time":"2022-05-23T00:00:00Z","timestamp":1653264000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Svend Helge Arvid Schr\u00f8der and Ketty Lydia Larsen Schr\u00f8der Foundation"},{"name":"Synoptik Foundation"},{"name":"\u201cFight for Sight, Denmark\u201d, the Faculty of Health and Medical Science, University of Copenhagen"},{"name":"Copenhagen University Hospital\u2014Rigshospitalet"},{"name":"Danish Eye Research Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>The pathogenesis of squamous cell neoplasms arising in the lacrimal drainage system is poorly understood, and the underlying genomic drivers for disease development remain unexplored. We aimed to investigate the genomic aberrations in carcinomas arising in the LDS and correlate the findings to human papillomavirus (HPV) status. The HPV analysis was performed using HPV DNA PCR, HPV E6\/E7 mRNA in-situ hybridization, and p16 immunohistochemistry. The genomic characterization was performed by targeted DNA sequencing of 523 cancer-relevant genes. Patients with LDS papilloma (n = 17) and LDS carcinoma (n = 15) were included. There was a male predominance (68%) and a median age at diagnosis of 46.0 years (range 27.5\u201365.5 years) in patients with papilloma and 63.8 years (range 34.0\u201387.2 years) in patients with carcinoma. Transcriptional activity of the HPV E6\/E7 oncogenes was detected in the whole tumor thickness in 12\/15 (80%) papillomas (HPV6, 11, 16) and 10\/15 (67%) squamous cell carcinomas (SCC) (HPV11: 3\/15 (20%) and HPV16: 7\/15 (47%)). Pathogenic variants in PIK3CA, FGFR3, AKT1, and PIK3R1, wildtype TP53, p16 overexpression, and deregulated high-risk E6\/E7 transcription characterized the HPV16-positive SCC. The deregulated pattern of HPV E6\/E7 expression, correlating with HPV DNA presence and p16 positivity, supports a causal role of HPV in a subset of LDS papillomas and carcinomas. The viral and molecular profile of LDS SCC resembles that of other HPV-driven SCC.<\/jats:p>","DOI":"10.3390\/cancers14102558","type":"journal-article","created":{"date-parts":[[2022,5,23]],"date-time":"2022-05-23T22:57:22Z","timestamp":1653346642000},"page":"2558","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Viral and Genomic Drivers of Squamous Cell Neoplasms Arising in the Lacrimal Drainage System"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4980-5905","authenticated-orcid":false,"given":"Ingvild","family":"Ramberg","sequence":"first","affiliation":[{"name":"The Eye Pathology Section, Department of Pathology, Copenhagen University Hospital Rigshospitalet, DK-2100 Copenhagen, Denmark"},{"name":"Department of Ophthalmology, Copenhagen University Hospital Rigshospitalet, DK-2100 Copenhagen, Denmark"},{"name":"Department of Clinical Medicine, Copenhagen University, DK-2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filipe Garrett","family":"Vieira","sequence":"additional","affiliation":[{"name":"Center for Genomic Medicine, Copenhagen University Hospital Rigshospitalet, DK-2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter Bjerre","family":"Toft","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Copenhagen University Hospital Rigshospitalet, DK-2100 Copenhagen, Denmark"},{"name":"Department of Clinical Medicine, Copenhagen University, DK-2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6753-8129","authenticated-orcid":false,"given":"Christian","family":"von Buchwald","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Copenhagen University, DK-2100 Copenhagen, Denmark"},{"name":"Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Copenhagen University Hospital Rigshospitalet, DK-2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steffen","family":"Heegaard","sequence":"additional","affiliation":[{"name":"The Eye Pathology Section, Department of Pathology, Copenhagen University Hospital Rigshospitalet, DK-2100 Copenhagen, Denmark"},{"name":"Department of Ophthalmology, Copenhagen University Hospital Rigshospitalet, DK-2100 Copenhagen, Denmark"},{"name":"Department of Clinical Medicine, Copenhagen University, DK-2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1016\/j.survophthal.2020.04.001","article-title":"Carcinomas of the lacrimal drainage system","volume":"6","author":"Ramberg","year":"2020","journal-title":"Surv. 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