{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:05:37Z","timestamp":1792789537346,"version":"4.5.0"},"reference-count":52,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,29]],"date-time":"2021-12-29T00:00:00Z","timestamp":1640736000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Folke Hermansen Fond","award":["year (2014-20219"],"award-info":[{"award-number":["year (2014-20219"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Implementation of high-risk human papilloma virus (HPV) screening and the increasing proportion of HPV vaccinated women in the screening program will reduce the percentage of HPV positive women with oncogenic potential. In search of more specific markers to identify women with high risk of cancer development, we used RNA sequencing to compare the transcriptomic immune-profile of 13 lesions with cervical intraepithelial neoplasia grade 3 (CIN3) or adenocarcinoma in situ (AIS) and 14 normal biopsies from women with detected HPV infections. In CIN3\/AIS lesions as compared to normal tissue, 27 differential expressed genes were identified. Transcriptomic analysis revealed significantly higher expression of a number of genes related to proliferation, (CDKN2A, MELK, CDK1, MKI67, CCNB2, BUB1, FOXM1, CDKN3), but significantly lower expression of genes related to a favorable immune response (NCAM1, ARG1, CD160, IL18, CX3CL1). Compared to the RNA sequencing results, good correlation was achieved with relative quantitative PCR analysis for NCAM1 and CDKN2A. Quantification of NCAM1 positive cells with immunohistochemistry showed epithelial reduction of NCAM1 in CIN3\/AIS lesions. In conclusion, NCAM1 and CDKN2A are two promising candidates to distinguish whether women are at high risk of developing cervical cancer and in need of frequent follow-up.<\/jats:p>","DOI":"10.3390\/ijms23010373","type":"journal-article","created":{"date-parts":[[2021,12,29]],"date-time":"2021-12-29T23:31:35Z","timestamp":1640820695000},"page":"373","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["High-Grade Cervical Intraepithelial Neoplasia (CIN) Associates with Increased Proliferation and Attenuated Immune Signaling"],"prefix":"10.3390","volume":"23","author":[{"given":"Irene Tveiter\u00e5s","family":"\u00d8vestad","sequence":"first","affiliation":[{"name":"Department of Pathology, Stavanger University Hospital, 4011 Stavanger, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgit","family":"Enges\u00e6ter","sequence":"additional","affiliation":[{"name":"Section for Cervical Cancer Screening, Cancer Registry of Norway, 0304 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2660-8271","authenticated-orcid":false,"given":"Mari Kylles\u00f8","family":"Halle","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Haukeland University Hospital, 5053 Bergen, Norway"},{"name":"Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, 5053 Bergen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saleha","family":"Akbari","sequence":"additional","affiliation":[{"name":"Department of Pathology, Stavanger University Hospital, 4011 Stavanger, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatrix","family":"Bicskei","sequence":"additional","affiliation":[{"name":"Department of Pathology, Stavanger University Hospital, 4011 Stavanger, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morten","family":"Lapin","sequence":"additional","affiliation":[{"name":"Department of Haematology and Oncology, Stavanger University Hospital, 4011 Stavanger, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Austdal","sequence":"additional","affiliation":[{"name":"Section of Biostatistics, Department of Research, Stavanger University Hospital, 4011 Stavanger, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7760-5396","authenticated-orcid":false,"given":"Emiel A. M.","family":"Janssen","sequence":"additional","affiliation":[{"name":"Department of Pathology, Stavanger University Hospital, 4011 Stavanger, Norway"},{"name":"Department of Chemistry, Bioscience and Environmental Technology, University of Stavanger, 4036 Stavanger, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0174-8139","authenticated-orcid":false,"given":"Camilla","family":"Krakstad","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Haukeland University Hospital, 5053 Bergen, Norway"},{"name":"Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, 5053 Bergen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melinda","family":"Lillesand","sequence":"additional","affiliation":[{"name":"Department of Pathology, Stavanger University Hospital, 4011 Stavanger, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marit","family":"Nordhus","sequence":"additional","affiliation":[{"name":"Department of Pathology, Stavanger University Hospital, 4011 Stavanger, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ane Cecilie","family":"Munk","sequence":"additional","affiliation":[{"name":"Department of Gynaecology, S\u00f8rlandet Hospital, 4604 Kristiansand, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Einar G.","family":"Gudlaugsson","sequence":"additional","affiliation":[{"name":"Department of Pathology, Stavanger University Hospital, 4011 Stavanger, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1016\/S0140-6736(07)61416-0","article-title":"Human papillomavirus and cervical cancer","volume":"370","author":"Schiffman","year":"2007","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"F24","DOI":"10.1016\/j.vaccine.2012.05.089","article-title":"Updating the Natural History of Human Papillomavirus and Anogenital Cancers","volume":"30","author":"Moscicki","year":"2012","journal-title":"Vaccine"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2629","DOI":"10.1002\/ijc.32195","article-title":"Recent increase in incidence of cervical precancerous lesions in Norway: Nationwide study from 1992 to 2016","volume":"145","author":"Orumaa","year":"2019","journal-title":"Int. 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