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Research Article| Volume 129, ISSUE 3, P246-259.e1, March 2020

Surrogate markers for high-risk human papillomavirus infection in oral epithelial dysplasia: A comparison of p16, Ki-67, and ProExC

  • Amr Alsabbagh
    Affiliations
    Department of Dentistry, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada
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  • Terry L. Robins
    Affiliations
    Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada

    Department of Pathology and Laboratory Medicine, London Health Sciences Centre, London, Ontario, Canada
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  • Ariel Harriman
    Affiliations
    Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada

    Department of Pathology and Laboratory Medicine, London Health Sciences Centre, London, Ontario, Canada
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  • Linda Jackson-Boeters
    Affiliations
    Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada

    Department of Pathology and Laboratory Medicine, London Health Sciences Centre, London, Ontario, Canada
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  • Mark R. Darling
    Affiliations
    Department of Dentistry, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada

    Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada

    Department of Pathology and Laboratory Medicine, London Health Sciences Centre, London, Ontario, Canada
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  • Zia A. Khan
    Affiliations
    Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada

    Department of Pathology and Laboratory Medicine, London Health Sciences Centre, London, Ontario, Canada
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  • Christina McCord
    Correspondence
    Reprint requests: Christina McCord Division of Oral Pathology Department of Pathology and Laboratory Medicine Western University 1151 Richmond Street HSA 418 A, London Ontario N6A 4C1 Canada.
    Affiliations
    Department of Dentistry, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada

    Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada

    Department of Pathology and Laboratory Medicine, London Health Sciences Centre, London, Ontario, Canada
    Search for articles by this author
Published:October 14, 2019DOI:https://doi.org/10.1016/j.oooo.2019.09.019

      Objective

      The aim of this study was to determine the utility of surrogate markers of human papillomavirus (HPV) infection in the diagnosis of HPV-associated oral epithelial dysplasia (OED).

      Study Design

      Twelve cases of oral dysplasia with histologic features of HPV infection were stained with surrogate markers for HPV (p16, Ki-67, and ProExC) on immunohistochemistry. A second group of 12 cases of oral dysplasia without histologic features of HPV infection was used for comparison. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to confirm the presence of high-risk HPV (HR HPV) in p16-positive cases.

      Results

      All of the surrogate markers showed a statistically significant association with HPV-positive OED (P < .001). The agreement between p16 and HPV positivity was the strongest (κ = 1.00), whereas Ki-67 showed very good association with HPV (κ = 0.83), and ProExC showed good association (κ = 0.75). In each case, the agreement was statistically significant (P < .001). Overall, each of the 3 markers showed good sensitivity; however, ProExC showed the lowest specificity.

      Conclusions

      The clinicopathologic features of 12 cases of HPV OED are reported. Diffuse p16 positivity is an accurate and reliable method for predicting HR HPV infection in both high and low grade cases of epithelial dysplasia with histopathologic features of HPV OED. The use of Ki-67 and ProExC did not demonstrate any additional diagnostic benefit in the diagnosis HPV OED.
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