{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T00:27:31Z","timestamp":1792715251645,"version":"4.5.0"},"reference-count":30,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2022,9,30]],"date-time":"2022-09-30T00:00:00Z","timestamp":1664496000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004337","name":"Roche","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004337","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Obstet Gynecol Scand"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Immunostaining with p16<jats:sup>INK4a<\/jats:sup> (p16), a tumor\u2010suppressor surrogate protein biomarker for high\u2010risk human papillomavirus (hrHPV) oncogenic activity, may complement standard hematoxylin and eosin (H&amp;E) histology review, and provide more objective criteria to support the cervical intraepithelial neoplasia (CIN) diagnosis. With this study we assessed the impact of p16 immunohistochemistry on CIN grading in an hrHPV\u2010based screening setting.<\/jats:p><\/jats:sec><jats:sec><jats:title>Material and methods<\/jats:title><jats:p>In this post\u2010hoc analysis, 326 histology follow\u2010up samples from a group of hrHPV\u2010positive women were stained with p16 immunohistochemistry. All H&amp;E samples were centrally revised. The pathologists reported their level of confidence in classifying the CIN lesion.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Combining H&amp;E and p16 staining resulted in a change of diagnosis in 27.3% (<jats:italic>n<\/jats:italic>\u00a0=\u00a089) of cases compared with the revised H&amp;E samples, with a decrease of 34.5% (<jats:italic>n<\/jats:italic>\u00a0=\u00a018) in CIN1 and 22.7% (<jats:italic>n<\/jats:italic>\u00a0=\u00a015) in CIN2 classifications, and an increase of 18.3% (<jats:italic>n<\/jats:italic>\u00a0=\u00a019) in no CIN and 20.7% (<jats:italic>n<\/jats:italic>\u00a0=\u00a019) in CIN3 diagnoses. The level of confidence in CIN grading by the pathologist increased with adjunctive use of p16 immunohistochemistry to standard H&amp;E.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study shows that adjunctive use of p16 immunohistochemistry to H&amp;E morphology reduces the number of CIN1 and CIN2 classifications with a proportional increase in no CIN and CIN3 diagnoses, compared with standard H&amp;E\u2010based CIN diagnosis alone. The pathologists felt more confident in classifying the material with H&amp;E and p16 immunohistochemistry than by using H&amp;E alone, particularly during assessment of small biopsies. Adjunctive use of p16 immunohistochemistry to standard H&amp;E assessment of CIN would be valuable for the diagnostic accuracy, thereby optimizing CIN management and possibly decreasing overtreatment.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aogs.14459","type":"journal-article","created":{"date-parts":[[2022,9,30]],"date-time":"2022-09-30T09:26:38Z","timestamp":1664529998000},"page":"1328-1336","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Adjunctive use of p16 immunohistochemistry for optimizing management of CIN lesions in a high\u2010risk human papillomavirus\u2010positive population"],"prefix":"10.1111","volume":"101","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3422-5086","authenticated-orcid":false,"given":"Ren\u00e9e M. F.","family":"Ebisch","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology Radboud University Medical Center  Nijmegen The Netherlands"},{"name":"Department of Obstetrics and Gynecology Catharina Hospital Eindhoven  Eindhoven The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. Lucia","family":"Rijstenberg","sequence":"additional","affiliation":[{"name":"Department of Pathology Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilda Ghazi","family":"Soltani","sequence":"additional","affiliation":[{"name":"Department of Pathology Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"van der Horst","sequence":"additional","affiliation":[{"name":"Department of Pathology Deventer Hospital  Deventer The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith E. M.","family":"Vedder","sequence":"additional","affiliation":[{"name":"Department of Pathology Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meyke","family":"Hermsen","sequence":"additional","affiliation":[{"name":"Department of Pathology Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Remko P.","family":"Bosgraaf","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Catharina Hospital Eindhoven  Eindhoven The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leon F. A. G.","family":"Massuger","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris J. L. M.","family":"Meijer","sequence":"additional","affiliation":[{"name":"Amsterdam UMC Vrije Universiteit Amsterdam, Pathology, Cancer Center Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dani\u00eblle A. M.","family":"Heideman","sequence":"additional","affiliation":[{"name":"Amsterdam UMC Vrije Universiteit Amsterdam, Pathology, Cancer Center Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Folkert J.","family":"van Kemenade","sequence":"additional","affiliation":[{"name":"Department of Pathology Erasmus University Medical Center  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Willem J. G.","family":"Melchers","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruud L. M.","family":"Bekkers","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Catharina Hospital Eindhoven  Eindhoven The Netherlands"},{"name":"GROW, School for Oncology and Developmental Biology Maastricht University  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert G.","family":"Siebers","sequence":"additional","affiliation":[{"name":"Department of Pathology Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"Bulten","sequence":"additional","affiliation":[{"name":"Department of Pathology Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,9,30]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(11)70296-0"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.21955"},{"key":"e_1_2_11_4_1","unstructured":"Landelijke monitoring Bevolkingsonderzoek Baarmoederhalskanker ErasmusMC en Palga Bevolkingsonderzoek baarmoederhalskanker monitor 2017 eerste resultaten van het vernieuwde bevolkingsonderzoek baarmoederhalskanker. 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Richtlijn CIN AIS en VAIN 2015 [Working group guideline CIN AEV. Guideline CIN AIS and VAIN 2015]In Dutch. Cited 2019 04\u201005\u20102019. 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