Consensus in Oral Epithelial Dysplasia Classification

Diagnosis and classification of oral epithelial dysplasia (OED) is critical to identifying and prognosticating patients at risk of squamous cell carcinoma (SCC). However, conventional 3-tiered and 2-tiered grading systems suffer from poor inter-pathologist agreement, and SCC may arise from all grades of OED. This study evaluated pathologist agreement in OED classification as p53 wildtype, p53 abnormal, and HPV-associated based on recent evidence demonstrating the utility of p53/p16 immunohistochemistry (IHC) in this setting and increased risk of p53 abnormal OED progression to SCC, regardless of histologic grade. Fifty digital biopsy specimens were evaluated for diagnosis by 18 subspecialty-trained pathologists, with OED graded utilizing 3-tiered, 2-tiered, and p53 wildtype/p53 abnormal/HPV-associated schemata. Cases were reviewed first without and subsequently with p53/p16 IHC. The cohort consisted of 8 cases of p53 wildtype, 24 cases of p53 abnormal, and 18 cases of HPV-associated OED. Inter-pathologist agreement in OED grading according to 3-tiered (κ=0.32) and 2-tiered (κ=0.39) systems by H&E was poor, but fair-to-good (κ=0.59) in classification as p53 wildtype/p53 abnormal/HPV-associated by H&E and IHC. Classification of OED as p53 wildtype, p53 abnormal, or HPV-associated using p53/p16 IHC outperformed conventional grading in this cohort enriched for p53 abnormal OED, which required correct interpretation of p53 IHC, historically deemed challenging. Routine use of IHC also identifies a wider histologic spectrum of HPV-associated OED than is currently appreciated. More work is needed to determine the efficacy of this classification system in predicting patient outcomes and in guiding management decisions in real-world cohorts.

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Publication Details

Journal
The American Journal of Surgical Pathology
Published
2025-04-09
DOI
https://doi.org/10.1097/pas.0000000000002385
Citations
5
Primary Topic
Oral Health Pathology and Treatment
Type
article
Field-Weighted Citation Impact
7.33
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article

Consensus in Oral Epithelial Dysplasia Classification

Yen Chen Kevin Ko, Emilija Todorovic, Chia‐Cheng Li, Elizabeth Ann Bilodeau et al.
5 citations
The American Journal of Surgical Pathology
Oral Health Pathology and Treatment
7.33
article

Consensus in Oral Epithelial Dysplasia Classification

Yen Chen Kevin Ko, Emilija Todorovic, Chia‐Cheng Li, Elizabeth Ann Bilodeau, Ilena Yim, Ivan J. Stojanov, Christina McCord, Paras Patel, Brandon Veremis, Hemlata Shirsat, Lynn Hoang, Christopher C. Griffith, William C. Faquin, Vincent Cracolici, Kelly Yi Ping Liu, Kelly R. Magliocca, Elizabeth Philipone, Martial Guillaud, Iona Leong, Yiping Wang, Lingxin Zhang, Julia Yu‐Fong Chang, William H. Westra, Victoria Woo, Natyra Haxhiavdija
article en
5 citations

Abstract

Diagnosis and classification of oral epithelial dysplasia (OED) is critical to identifying and prognosticating patients at risk of squamous cell carcinoma (SCC). However, conventional 3-tiered and 2-tiered grading systems suffer from poor inter-pathologist agreement, and SCC may arise from all grades of OED. This study evaluated pathologist agreement in OED classification as p53 wildtype, p53 abnormal, and HPV-associated based on recent evidence demonstrating the utility of p53/p16 immunohistochemistry (IHC) in this setting and increased risk of p53 abnormal OED progression to SCC, regardless of histologic grade. Fifty digital biopsy specimens were evaluated for diagnosis by 18 subspecialty-trained pathologists, with OED graded utilizing 3-tiered, 2-tiered, and p53 wildtype/p53 abnormal/HPV-associated schemata. Cases were reviewed first without and subsequently with p53/p16 IHC. The cohort consisted of 8 cases of p53 wildtype, 24 cases of p53 abnormal, and 18 cases of HPV-associated OED. Inter-pathologist agreement in OED grading according to 3-tiered (κ=0.32) and 2-tiered (κ=0.39) systems by H&E was poor, but fair-to-good (κ=0.59) in classification as p53 wildtype/p53 abnormal/HPV-associated by H&E and IHC. Classification of OED as p53 wildtype, p53 abnormal, or HPV-associated using p53/p16 IHC outperformed conventional grading in this cohort enriched for p53 abnormal OED, which required correct interpretation of p53 IHC, historically deemed challenging. Routine use of IHC also identifies a wider histologic spectrum of HPV-associated OED than is currently appreciated. More work is needed to determine the efficacy of this classification system in predicting patient outcomes and in guiding management decisions in real-world cohorts.

The American Journal of Surgical PathologyVol. 49(6)
Western University (CA), Cleveland Clinic (US), Harvard University (US), University of British Columbia (CA), Emory University (US), National Taiwan University (TW), University of Calgary (CA), University of Toronto (CA), Columbia University Irving Medical Center (US), Spinal Cord Injury BC (CA), Vancouver General Hospital (CA), Massachusetts General Hospital (US), Calgary Laboratory Services (CA), Propath Services (United States) (US), Mount Sinai Hospital (US), Institute of Clinical Research (US), National Taiwan University Hospital (TW), Institute of Infection and Immunity (CA), Texas A&M University (US), Icahn School of Medicine at Mount Sinai (US)
No poverty
Openalex Percentile: Top 3%
Oral Health Pathology and Treatment
7.33
DOISourceOpenAlex
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