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 Article


Authors: Ren, H.; Pors, J.; Chow, C.; Ta, M.; Stolnicu, S.; Soslow, R.; Huntsman, D.; Hoang, L.
Article 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
Abstract: 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. © 2020 The Korean Society of Pathologists.
Keywords: immunohistochemistry; controlled study; human tissue; human cell; major clinical study; cancer recurrence; disease classification; nonhuman; neoadjuvant therapy; diagnostic accuracy; adenocarcinoma; protein p16; in situ hybridization; neutrophil; virus rna; cytoplasm; tissue microarray; estrogen receptor; electrosurgery; tumor classification; signal detection; cervix; uterine cervix biopsy; uterine cervix carcinoma; p16; wart virus; uterine cervix carcinoma in situ; vimentin; mucin; in-situ hybridization; rna probe; human papillomavirus; diagnostic test accuracy study; papillomavirus infection; adenocarcinoma in situ; human; female; article; iecc; international endocervical adenocarcinoma criteria and classification; international endocervical adenocarcinoma ariteria and classification
Journal Title: Journal of Pathology and Translational Medicine
Volume: 54
Issue: 6
ISSN: 2383-7837
Publisher: The Korean Society of Pathologists  
Date Published: 2020-11-01
Start Page: 480
End Page: 488
Language: English
DOI: 10.4132/jptm.2020.07.18
PROVIDER: scopus
PMCID: PMC7674758
PUBMED: 32854489
DOI/URL:
Notes: Article -- Export Date: 1 February 2021 -- Source: Scopus
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  1. Robert Soslow
    793 Soslow