{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T16:57:55Z","timestamp":1791219475725,"version":"4.1.0"},"reference-count":17,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2015,4,27]],"date-time":"2015-04-27T00:00:00Z","timestamp":1430092800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002661","name":"Fonds De La Recherche Scientifique - FNRS","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002661","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fonds Leon Fredericq"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2015,7]]},"abstract":"Abstract<\/jats:title>\n \n Recent studies have suggested the involvement of a unique population of cells at the cervical squamo\u2010columnar junction (\n SCJ<\/jats:styled-content>\n ) in the pathogenesis of early (squamous intraepithelial lesion or\n SIL<\/jats:styled-content>\n ) and advanced (squamous cell and adeno\u2010carcinomas) cervical neoplasia. However, there is little evidence to date showing that\n SCJ<\/jats:styled-content>\n cells harbour carcinogenic\n HPV<\/jats:styled-content>\n or are instrumental in the initial phases of neoplasia. This study was designed to (1) determine if normal\u2010appearing\n SCJ<\/jats:styled-content>\n cells contained evidence of carcinogenic\n HPV<\/jats:styled-content>\n infection and (2) trace their transition to early\n SIL<\/jats:styled-content>\n . Sections of cervix from high\u2010risk reproductive age women were selected and\n SCJ<\/jats:styled-content>\n cells were analysed by using several techniques which increasingly implicated\n HPV<\/jats:styled-content>\n infection:\n HPV DNA<\/jats:styled-content>\n (genotyping and\n in situ<\/jats:italic>\n hybridization)\/\n RNA<\/jats:styled-content>\n (\n PCR<\/jats:styled-content>\n ), immunostaining for\n HPV16 E2<\/jats:styled-content>\n (an early marker of\n HPV<\/jats:styled-content>\n infection), p16\n ink4<\/jats:sup>\n , Ki67, and\n HPV L1<\/jats:styled-content>\n protein. In 22 cases with a history of\n SIL<\/jats:styled-content>\n and no evidence of preneoplastic lesion in the excision specimen,\n HPV DNA<\/jats:styled-content>\n was isolated from eight of ten with visible\n SCJ<\/jats:styled-content>\n cells, six of which were\n HPV16<\/jats:styled-content>\n \/18\n DNA<\/jats:styled-content>\n \u2010positive. In five of these latter cases, the\n SCJ<\/jats:styled-content>\n cells were positive for p16\n ink4<\/jats:sup>\n and\/or\n HPV E2<\/jats:styled-content>\n . Transcriptionally active\n HPV<\/jats:styled-content>\n infection (\n E6<\/jats:styled-content>\n \/\n E7 mRNAs<\/jats:styled-content>\n ) was also detected in microdissected\n SCJ<\/jats:styled-content>\n cells. Early squamous atypia associated with the\n SCJ<\/jats:styled-content>\n cells demonstrated in addition diffuse p16\n ink4<\/jats:sup>\n immunoreactivity, elevated proliferative index, and rare\n L1<\/jats:styled-content>\n antigen positivity. We present for the first time direct evidence that normal\u2010appearing\n SCJ<\/jats:styled-content>\n cells can be infected by carcinogenic\n HPV<\/jats:styled-content>\n . They initially express\n HPV E2<\/jats:styled-content>\n and their progression to\n SIL<\/jats:styled-content>\n is heralded by an expanding metaplastic progeny with increased proliferation and p16\n ink4<\/jats:sup>\n expression. Whether certain\n SCJs<\/jats:styled-content>\n are more vulnerable than others to carcinogenic\n HPV<\/jats:styled-content>\n genotypes and what variables determine transition to high\u2010grade\n SIL<\/jats:styled-content>\n remain unresolved, but the common event appears to be a vulnerable cell at the\n SCJ<\/jats:styled-content>\n . Copyright \u00a9 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.\n <\/jats:p>","DOI":"10.1002\/path.4533","type":"journal-article","created":{"date-parts":[[2015,3,18]],"date-time":"2015-03-18T03:55:11Z","timestamp":1426650911000},"page":"265-271","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":74,"title":["Carcinogenic HPV infection in the cervical squamo\u2010columnar junction"],"prefix":"10.1002","volume":"236","author":[{"given":"Jelena","family":"Mirkovic","sequence":"first","affiliation":[{"name":"Department of Pathology, Division of Women's and Perinatal Pathology Brigham and Women's Hospital Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brooke E","family":"Howitt","sequence":"additional","affiliation":[{"name":"Department of Pathology, Division of Women's and Perinatal Pathology Brigham and Women's Hospital Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Roncarati","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Pathology, GIGA\u2010Cancer University of Li\u00e8ge Li\u00e8ge Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Demoulin","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Pathology, GIGA\u2010Cancer University of Li\u00e8ge Li\u00e8ge Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meggy","family":"Suarez\u2010Carmona","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Pathology, GIGA\u2010Cancer University of Li\u00e8ge Li\u00e8ge Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascale","family":"Hubert","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Pathology, GIGA\u2010Cancer University of Li\u00e8ge Li\u00e8ge Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank D","family":"McKeon","sequence":"additional","affiliation":[{"name":"Jackson Laboratory for Genomic Medicine Farmington CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wa","family":"Xian","sequence":"additional","affiliation":[{"name":"Jackson Laboratory for Genomic Medicine Farmington CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathology, Division of Women's and Perinatal Pathology Brigham and Women's Hospital Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Delvenne","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Pathology, GIGA\u2010Cancer University of Li\u00e8ge Li\u00e8ge Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher P","family":"Crum","sequence":"additional","affiliation":[{"name":"Department of Pathology, Division of Women's and Perinatal Pathology Brigham and Women's Hospital Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Herfs","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Pathology, GIGA\u2010Cancer University of Li\u00e8ge Li\u00e8ge Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,4,27]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"444","article-title":"Original site of cervical carcinoma; 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