Evaluation of human papillomavirus (HPV) prediction using the International Endocervical Adenocarcinoma Criteria and Classification system, compared to p16 immunohistochemistry and HPV RNA in-situ hybridization

Background The International Endocervical Adenocarcinoma Criteria and Classification (IECC) separated endocervical adenocarcinomas into human papillomavirus (HPV) associated (HPVA) and non–HPV-associated (NHPVA) categories by morphology alone. Our primary objective was to assess the accuracy of HPV...

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Main Authors: Hezhen Ren, Jennifer Pors, Christine Chow, Monica Ta, Simona Stolnicu, Robert Soslow, David Huntsman, Lynn Hoang
Format: Article
Language:English
Published: Korean Society of Pathologists & the Korean Society for Cytopathology 2020-11-01
Series:Journal of Pathology and Translational Medicine
Subjects:
Online Access:http://www.jpatholtm.org/upload/pdf/jptm-2020-07-18.pdf
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author Hezhen Ren
Jennifer Pors
Christine Chow
Monica Ta
Simona Stolnicu
Robert Soslow
David Huntsman
Lynn Hoang
author_facet Hezhen Ren
Jennifer Pors
Christine Chow
Monica Ta
Simona Stolnicu
Robert Soslow
David Huntsman
Lynn Hoang
author_sort Hezhen Ren
collection DOAJ
description Background The International Endocervical Adenocarcinoma Criteria and Classification (IECC) separated endocervical adenocarcinomas into human papillomavirus (HPV) associated (HPVA) and non–HPV-associated (NHPVA) categories by morphology alone. Our primary objective was to assess the accuracy of HPV prediction by the IECC system compared to p16 immunohistochemistry and HPV RNA in-situ hybridization (RISH). Our secondary goal was to directly compare p16 and HPV RISH concordance. Methods Cases were classified by IECC and stained for p16 and HPV RISH on tissue microarray, with discordant p16/HPV RISH cases re-stained on whole tissue sections. Remaining discordant cases (p16/HPV, IECC/p16, IECC/HPV discordances) were re-reviewed by the original pathologists (n = 3) and external expert pathologists (n = 2) blinded to the p16 and HPV RISH results. Final IECC diagnosis was assigned upon independent agreement between all reviewers. Results One hundred and eleven endocervical adenocarcinomas were classified originally into 94 HPVA and 17 NHPVA cases. p16 and HPV RISH was concordant in 108/111 cases (97%) independent of the IECC. HPV RISH and p16 was concordant with IECC in 103/111 (93%) and 106/111 (95%), respectively. After expert review, concordance improved to 107/111 (96%) for HPV RISH. After review of the eight discordant cases, one remained as HPVA, four were reclassified to NHPVA from HPVA, two were unclassifiable, and one possibly represented a mixed usual and gastric-type adenocarcinoma. Conclusions p16 and HPV RISH have excellent concordance in endocervical adenocarcinomas, and IECC can predict HPV status in most cases. Focal apical mitoses and apoptotic debris on original review led to the misclassification of several NHPVA as HPVA.
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spelling doaj.art-36b9fcc54cf841c0b8e4f1588aae49f92022-12-21T21:14:31ZengKorean Society of Pathologists & the Korean Society for CytopathologyJournal of Pathology and Translational Medicine2383-78372383-78452020-11-0154648048810.4132/jptm.2020.07.1816929Evaluation of human papillomavirus (HPV) prediction using the International Endocervical Adenocarcinoma Criteria and Classification system, compared to p16 immunohistochemistry and HPV RNA in-situ hybridizationHezhen Ren0Jennifer Pors1Christine Chow2Monica Ta3Simona Stolnicu4Robert Soslow5David Huntsman6Lynn Hoang7 Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada Genetic Pathology Evaluation Center (GPEC), Vancouver, BC, Canada Genetic Pathology Evaluation Center (GPEC), Vancouver, BC, Canada Department of Pathology, University of Medicine, Pharmacy, Sciences and Technology of Targu Mures, Targu Mures, Romania Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, CanadaBackground The International Endocervical Adenocarcinoma Criteria and Classification (IECC) separated endocervical adenocarcinomas into human papillomavirus (HPV) associated (HPVA) and non–HPV-associated (NHPVA) categories by morphology alone. Our primary objective was to assess the accuracy of HPV prediction by the IECC system compared to p16 immunohistochemistry and HPV RNA in-situ hybridization (RISH). Our secondary goal was to directly compare p16 and HPV RISH concordance. Methods Cases were classified by IECC and stained for p16 and HPV RISH on tissue microarray, with discordant p16/HPV RISH cases re-stained on whole tissue sections. Remaining discordant cases (p16/HPV, IECC/p16, IECC/HPV discordances) were re-reviewed by the original pathologists (n = 3) and external expert pathologists (n = 2) blinded to the p16 and HPV RISH results. Final IECC diagnosis was assigned upon independent agreement between all reviewers. Results One hundred and eleven endocervical adenocarcinomas were classified originally into 94 HPVA and 17 NHPVA cases. p16 and HPV RISH was concordant in 108/111 cases (97%) independent of the IECC. HPV RISH and p16 was concordant with IECC in 103/111 (93%) and 106/111 (95%), respectively. After expert review, concordance improved to 107/111 (96%) for HPV RISH. After review of the eight discordant cases, one remained as HPVA, four were reclassified to NHPVA from HPVA, two were unclassifiable, and one possibly represented a mixed usual and gastric-type adenocarcinoma. Conclusions p16 and HPV RISH have excellent concordance in endocervical adenocarcinomas, and IECC can predict HPV status in most cases. Focal apical mitoses and apoptotic debris on original review led to the misclassification of several NHPVA as HPVA.http://www.jpatholtm.org/upload/pdf/jptm-2020-07-18.pdfp16human papillomavirusimmunohistochemistryin-situ hybridizationcervixadenocarcinomainternational endocervical adenocarcinoma criteria and classificationiecc
spellingShingle Hezhen Ren
Jennifer Pors
Christine Chow
Monica Ta
Simona Stolnicu
Robert Soslow
David Huntsman
Lynn Hoang
Evaluation of human papillomavirus (HPV) prediction using the International Endocervical Adenocarcinoma Criteria and Classification system, compared to p16 immunohistochemistry and HPV RNA in-situ hybridization
Journal of Pathology and Translational Medicine
p16
human papillomavirus
immunohistochemistry
in-situ hybridization
cervix
adenocarcinoma
international endocervical adenocarcinoma criteria and classification
iecc
title Evaluation of human papillomavirus (HPV) prediction using the International Endocervical Adenocarcinoma Criteria and Classification system, compared to p16 immunohistochemistry and HPV RNA in-situ hybridization
title_full Evaluation of human papillomavirus (HPV) prediction using the International Endocervical Adenocarcinoma Criteria and Classification system, compared to p16 immunohistochemistry and HPV RNA in-situ hybridization
title_fullStr Evaluation of human papillomavirus (HPV) prediction using the International Endocervical Adenocarcinoma Criteria and Classification system, compared to p16 immunohistochemistry and HPV RNA in-situ hybridization
title_full_unstemmed Evaluation of human papillomavirus (HPV) prediction using the International Endocervical Adenocarcinoma Criteria and Classification system, compared to p16 immunohistochemistry and HPV RNA in-situ hybridization
title_short Evaluation of human papillomavirus (HPV) prediction using the International Endocervical Adenocarcinoma Criteria and Classification system, compared to p16 immunohistochemistry and HPV RNA in-situ hybridization
title_sort evaluation of human papillomavirus hpv prediction using the international endocervical adenocarcinoma criteria and classification system compared to p16 immunohistochemistry and hpv rna in situ hybridization
topic p16
human papillomavirus
immunohistochemistry
in-situ hybridization
cervix
adenocarcinoma
international endocervical adenocarcinoma criteria and classification
iecc
url http://www.jpatholtm.org/upload/pdf/jptm-2020-07-18.pdf
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