Classification of high-grade cervical intraepithelial neoplasia by p16 ink4a , Ki-67, HPV E4 and FAM19A4/miR124-2 methylation status demonstrates considerable heterogeneity with potential consequences for management

High-grade cervical intraepithelial neoplasia (CIN2 and CIN3) represents a heterogeneous disease with varying cancer progression risks. Biomarkers indicative for a productive human papillomavirus (HPV) infection (HPV E4) and a transforming HPV infection (p16 , Ki-67 and host-cell DNA methylation) co...

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Published in:International journal of cancer 2021-08, Vol.149 (3), p.707-716
Main Authors: Vink, Frederique J, Dick, Stèfanie, Heideman, Daniëlle A M, De Strooper, Lise M A, Steenbergen, Renske D M, Lissenberg-Witte, Birgit I, Floore, Arno, Bonde, Jesper H, Oštrbenk Valenčak, Anja, Poljak, Mario, Petry, Karl U, Hillemanns, Peter, van Trommel, Nienke E, Berkhof, Johannes, Bleeker, Maaike C G, Meijer, Chris J L M
Format: Article
Language:English
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Summary:High-grade cervical intraepithelial neoplasia (CIN2 and CIN3) represents a heterogeneous disease with varying cancer progression risks. Biomarkers indicative for a productive human papillomavirus (HPV) infection (HPV E4) and a transforming HPV infection (p16 , Ki-67 and host-cell DNA methylation) could provide guidance for clinical management in women with high-grade CIN. This study evaluates the cumulative score of immunohistochemical expression of p16 (Scores 0-3) and Ki-67 (Scores 0-3), referred to as the "immunoscore" (IS), in 262 CIN2 and 235 CIN3 lesions derived from five European cohorts in relation to immunohistochemical HPV E4 expression and FAM19A4/miR124-2 methylation in the corresponding cervical scrape. The immunoscore classification resulted in 30 lesions within IS group 0-2 (6.0%), 151 lesions within IS group 3-4 (30.4%) and 316 lesions within IS group 5-6 (63.6%). E4 expression decreased significantly from CIN2 to CIN3 (P
ISSN:0020-7136
1097-0215
DOI:10.1002/ijc.33566