Inter-observer Variability in the Diagnosis of Proliferative Verrucous Leukoplakia: Clinical Implications for Oral and Maxillofacial Surgeon Understanding: A Collaborative Pilot Study

  • Jasbir D. UpadhyayaEmail author
  • Sarah G. Fitzpatrick
  • Donald M. Cohen
  • Elizabeth A. Bilodeau
  • Indraneel Bhattacharyya
  • James S. LewisJr.
  • Jinping Lai
  • John M. Wright
  • Justin A. Bishop
  • Marino E. Leon
  • Mohammed N. Islam
  • Raja Seethala
  • Ricardo J. Padilla
  • Roman Carlos
  • Susan Müller
  • Lester D. R. Thompson
Original Paper


The use of diverse terminology may lead to inconsistent diagnosis and subsequent mistreatment of lesions within the proliferative verrucous leukoplakia (PVL) spectrum. The objectives of this study were: (a) to measure inter-observer variability between a variety of pathologists diagnosing PVL lesions; and (b) to evaluate the impact of diverse terminologies on understanding, interpretation, and subsequent treatment planning by oral and maxillofacial surgeons (OMFS). Six oral pathologists (OP) and six head and neck pathologists (HNP) reviewed 40 digitally scanned slides of PVL-type lesions. Inter-observer agreement on diagnoses was evaluated by Fleiss’ kappa analysis. The most commonly used diagnostic terminologies were sent to ten OMFS to evaluate their resulting interpretations and potential follow-up treatment approaches. The overall means of the surgeons’ responses were compared by Student t test. There was poor inter-observer agreement between pathologists on the diagnosis of PVL lesions (κ = 0.270), although there was good agreement (κ = 0.650) when diagnosing frankly malignant lesions. The lowest agreement was in diagnosing verrucous hyperplasia (VH) with/without dysplasia, atypical epithelial proliferation (AEP), and verrucous carcinoma (VC). The OMFS showed the lowest agreement on identical categories of non-malignant diagnoses, specifically VH and AEP. This study demonstrates a lack of standardized terminology and diagnostic criteria for the spectrum of PVL lesions. We recommend adopting standardized criteria and terminology, proposed and established by an expert panel white paper, to assist pathologists and clinicians in uniformly diagnosing and managing PVL spectrum lesions.


Inter-observer variability Proliferative verrucous leukoplakia Verrucous hyperplasia Papillary squamous cell carcinoma Atypical epithelial proliferation 



The authors are thankful to Drs. John Hardeman, University of Florida College of Dentistry; Andrew Salama, Boston University Henry M. Goldman School of Dental Medicine; Bradley Szutz, Alaska Oral and Facial Cosmetic Surgery, Anchorage, AK; Michael McDermott, Midwest Oral & Maxillofacial Surgery, Omaha, NE; Ravi Chandran, University of Mississipi Medical Center, Jackson, MS; George Kushner, University of Louisville School of Dentistry; Eric Fox, Oral Surgey Coral Springs, FL; Michael Langan, Central Florida Oral & Maxillofacial Surgery; Danielle Freburg-Hoffmeister, University of Florida College of Dentistry; and Carl Kimbler, Northern Plains Oral & Maxillofacial, Aberdeen, SD, for their participation in the oral and maxillofacial surgeon survey.

Compliance with Ethical Standards

Conflict of interest

All authors declare that they have no conflict of interest as it relates to this research project.

Ethical Approval

All procedures performed in this retrospective data analysis involving human participants were in accordance with the ethical standards of the institutional review board, which did not require informed consent.

Supplementary material

12105_2019_1035_MOESM1_ESM.docx (90 kb)
Supplementary material 1 (DOCX 89 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Jasbir D. Upadhyaya
    • 1
    Email author
  • Sarah G. Fitzpatrick
    • 2
  • Donald M. Cohen
    • 2
  • Elizabeth A. Bilodeau
    • 3
  • Indraneel Bhattacharyya
    • 2
  • James S. LewisJr.
    • 4
  • Jinping Lai
    • 5
  • John M. Wright
    • 6
  • Justin A. Bishop
    • 7
  • Marino E. Leon
    • 5
  • Mohammed N. Islam
    • 2
  • Raja Seethala
    • 8
  • Ricardo J. Padilla
    • 9
  • Roman Carlos
    • 10
  • Susan Müller
    • 11
  • Lester D. R. Thompson
    • 12
  1. 1.Section of Diagnostic Sciences, Department of Applied Dental MedicineSouthern Illinois University School of Dental MedicineAltonUSA
  2. 2.Department of Oral and Maxillofacial Diagnostic SciencesUniversity of Florida College of DentistryGainesvilleUSA
  3. 3.Department of Diagnostic SciencesUniversity of Pittsburgh School of Dental MedicinePittsburghUSA
  4. 4.Department of Pathology, Microbiology, and ImmunologyVanderbilt University Medical CenterNashvilleUSA
  5. 5.Department of Pathology, Immunology and Laboratory MedicineUniversity of Florida College of MedicineGainesvilleUSA
  6. 6.Department of Diagnostic SciencesTexas A&M College of DentistryDallasUSA
  7. 7.Department of PathologyUniversity of Texas Southwestern Medical CenterDallasUSA
  8. 8.Department of PathologyUniversity of PittsburghPittsburghUSA
  9. 9.Department of Diagnostic Sciences, School of DentistryUniversity of North Carolina at Chapel HillChapel HillUSA
  10. 10.Pathology DivisionCentro Clínico de Cabeza y CuelloGuatemala CityGuatemala
  11. 11.Emory University School of MedicineAtlanta Oral PathologyDecaturUSA
  12. 12.Southern California Permanente Medical GroupWoodland Hills Medical CenterWoodland HillsUSA

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