Adjunctive use of p16 immunohistochemistry for optimizing management of CIN lesions in a high‐risk human papillomavirus‐positive population

Abstract Introduction Immunostaining with p16INK4a (p16), a tumor‐suppressor surrogate protein biomarker for high‐risk human papillomavirus (hrHPV) oncogenic activity, may complement standard hematoxylin and eosin (H&E) histology review, and provide more objective criteria to support the cervica...

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Main Authors: Renée M. F. Ebisch, L. Lucia Rijstenberg, Gilda Ghazi Soltani, Judith van derHorst, Judith E. M. Vedder, Meyke Hermsen, Remko P. Bosgraaf, Leon F. A. G. Massuger, Chris J. L. M. Meijer, Daniëlle A. M. Heideman, Folkert J. vanKemenade, Willem J. G. Melchers, Ruud L. M. Bekkers, Albert G. Siebers, Johan Bulten
Format: Article
Language:English
Published: Wiley 2022-11-01
Series:Acta Obstetricia et Gynecologica Scandinavica
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Online Access:https://doi.org/10.1111/aogs.14459
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author Renée M. F. Ebisch
L. Lucia Rijstenberg
Gilda Ghazi Soltani
Judith van derHorst
Judith E. M. Vedder
Meyke Hermsen
Remko P. Bosgraaf
Leon F. A. G. Massuger
Chris J. L. M. Meijer
Daniëlle A. M. Heideman
Folkert J. vanKemenade
Willem J. G. Melchers
Ruud L. M. Bekkers
Albert G. Siebers
Johan Bulten
author_facet Renée M. F. Ebisch
L. Lucia Rijstenberg
Gilda Ghazi Soltani
Judith van derHorst
Judith E. M. Vedder
Meyke Hermsen
Remko P. Bosgraaf
Leon F. A. G. Massuger
Chris J. L. M. Meijer
Daniëlle A. M. Heideman
Folkert J. vanKemenade
Willem J. G. Melchers
Ruud L. M. Bekkers
Albert G. Siebers
Johan Bulten
author_sort Renée M. F. Ebisch
collection DOAJ
description Abstract Introduction Immunostaining with p16INK4a (p16), a tumor‐suppressor surrogate protein biomarker for high‐risk human papillomavirus (hrHPV) oncogenic activity, may complement standard hematoxylin and eosin (H&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‐based screening setting. Material and methods In this post‐hoc analysis, 326 histology follow‐up samples from a group of hrHPV‐positive women were stained with p16 immunohistochemistry. All H&E samples were centrally revised. The pathologists reported their level of confidence in classifying the CIN lesion. Results Combining H&E and p16 staining resulted in a change of diagnosis in 27.3% (n = 89) of cases compared with the revised H&E samples, with a decrease of 34.5% (n = 18) in CIN1 and 22.7% (n = 15) in CIN2 classifications, and an increase of 18.3% (n = 19) in no CIN and 20.7% (n = 19) in CIN3 diagnoses. The level of confidence in CIN grading by the pathologist increased with adjunctive use of p16 immunohistochemistry to standard H&E. Conclusions This study shows that adjunctive use of p16 immunohistochemistry to H&E morphology reduces the number of CIN1 and CIN2 classifications with a proportional increase in no CIN and CIN3 diagnoses, compared with standard H&E‐based CIN diagnosis alone. The pathologists felt more confident in classifying the material with H&E and p16 immunohistochemistry than by using H&E alone, particularly during assessment of small biopsies. Adjunctive use of p16 immunohistochemistry to standard H&E assessment of CIN would be valuable for the diagnostic accuracy, thereby optimizing CIN management and possibly decreasing overtreatment.
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spelling doaj-art-c2c33879154641e1a5fe25ca043b3de52025-08-20T02:09:28ZengWileyActa Obstetricia et Gynecologica Scandinavica0001-63491600-04122022-11-01101111328133610.1111/aogs.14459Adjunctive use of p16 immunohistochemistry for optimizing management of CIN lesions in a high‐risk human papillomavirus‐positive populationRenée M. F. Ebisch0L. Lucia Rijstenberg1Gilda Ghazi Soltani2Judith van derHorst3Judith E. M. Vedder4Meyke Hermsen5Remko P. Bosgraaf6Leon F. A. G. Massuger7Chris J. L. M. Meijer8Daniëlle A. M. Heideman9Folkert J. vanKemenade10Willem J. G. Melchers11Ruud L. M. Bekkers12Albert G. Siebers13Johan Bulten14Department of Obstetrics and Gynecology Radboud University Medical Center Nijmegen The NetherlandsDepartment of Pathology Radboud University Medical Center Nijmegen The NetherlandsDepartment of Pathology Radboud University Medical Center Nijmegen The NetherlandsDepartment of Pathology Deventer Hospital Deventer The NetherlandsDepartment of Pathology Radboud University Medical Center Nijmegen The NetherlandsDepartment of Pathology Radboud University Medical Center Nijmegen The NetherlandsDepartment of Obstetrics and Gynecology Catharina Hospital Eindhoven Eindhoven The NetherlandsDepartment of Obstetrics and Gynecology Radboud University Medical Center Nijmegen The NetherlandsAmsterdam UMC Vrije Universiteit Amsterdam, Pathology, Cancer Center Amsterdam Amsterdam The NetherlandsAmsterdam UMC Vrije Universiteit Amsterdam, Pathology, Cancer Center Amsterdam Amsterdam The NetherlandsDepartment of Pathology Erasmus University Medical Center Rotterdam The NetherlandsDepartment of Medical Microbiology Radboud University Medical Center Nijmegen The NetherlandsDepartment of Obstetrics and Gynecology Catharina Hospital Eindhoven Eindhoven The NetherlandsDepartment of Pathology Radboud University Medical Center Nijmegen The NetherlandsDepartment of Pathology Radboud University Medical Center Nijmegen The NetherlandsAbstract Introduction Immunostaining with p16INK4a (p16), a tumor‐suppressor surrogate protein biomarker for high‐risk human papillomavirus (hrHPV) oncogenic activity, may complement standard hematoxylin and eosin (H&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‐based screening setting. Material and methods In this post‐hoc analysis, 326 histology follow‐up samples from a group of hrHPV‐positive women were stained with p16 immunohistochemistry. All H&E samples were centrally revised. The pathologists reported their level of confidence in classifying the CIN lesion. Results Combining H&E and p16 staining resulted in a change of diagnosis in 27.3% (n = 89) of cases compared with the revised H&E samples, with a decrease of 34.5% (n = 18) in CIN1 and 22.7% (n = 15) in CIN2 classifications, and an increase of 18.3% (n = 19) in no CIN and 20.7% (n = 19) in CIN3 diagnoses. The level of confidence in CIN grading by the pathologist increased with adjunctive use of p16 immunohistochemistry to standard H&E. Conclusions This study shows that adjunctive use of p16 immunohistochemistry to H&E morphology reduces the number of CIN1 and CIN2 classifications with a proportional increase in no CIN and CIN3 diagnoses, compared with standard H&E‐based CIN diagnosis alone. The pathologists felt more confident in classifying the material with H&E and p16 immunohistochemistry than by using H&E alone, particularly during assessment of small biopsies. Adjunctive use of p16 immunohistochemistry to standard H&E assessment of CIN would be valuable for the diagnostic accuracy, thereby optimizing CIN management and possibly decreasing overtreatment.https://doi.org/10.1111/aogs.14459cervical cancercervical intraepithelial neoplasiahuman papillomavirusimmunohistochemistryp16
spellingShingle Renée M. F. Ebisch
L. Lucia Rijstenberg
Gilda Ghazi Soltani
Judith van derHorst
Judith E. M. Vedder
Meyke Hermsen
Remko P. Bosgraaf
Leon F. A. G. Massuger
Chris J. L. M. Meijer
Daniëlle A. M. Heideman
Folkert J. vanKemenade
Willem J. G. Melchers
Ruud L. M. Bekkers
Albert G. Siebers
Johan Bulten
Adjunctive use of p16 immunohistochemistry for optimizing management of CIN lesions in a high‐risk human papillomavirus‐positive population
Acta Obstetricia et Gynecologica Scandinavica
cervical cancer
cervical intraepithelial neoplasia
human papillomavirus
immunohistochemistry
p16
title Adjunctive use of p16 immunohistochemistry for optimizing management of CIN lesions in a high‐risk human papillomavirus‐positive population
title_full Adjunctive use of p16 immunohistochemistry for optimizing management of CIN lesions in a high‐risk human papillomavirus‐positive population
title_fullStr Adjunctive use of p16 immunohistochemistry for optimizing management of CIN lesions in a high‐risk human papillomavirus‐positive population
title_full_unstemmed Adjunctive use of p16 immunohistochemistry for optimizing management of CIN lesions in a high‐risk human papillomavirus‐positive population
title_short Adjunctive use of p16 immunohistochemistry for optimizing management of CIN lesions in a high‐risk human papillomavirus‐positive population
title_sort adjunctive use of p16 immunohistochemistry for optimizing management of cin lesions in a high risk human papillomavirus positive population
topic cervical cancer
cervical intraepithelial neoplasia
human papillomavirus
immunohistochemistry
p16
url https://doi.org/10.1111/aogs.14459
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