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

Amr Alsabbagh; Terry L Robins; Ariel Harriman; Linda Jackson-Boeters; Mark R Darling; Zia A Khan; Christina McCord

doi:10.1016/j.oooo.2019.09.019

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

Oral Surg Oral Med Oral Pathol Oral Radiol. 2020 Mar;129(3):246-259.e1. doi: 10.1016/j.oooo.2019.09.019. Epub 2019 Oct 14.

Authors

Amr Alsabbagh¹, Terry L Robins², Ariel Harriman², Linda Jackson-Boeters², Mark R Darling³, Zia A Khan², Christina McCord⁴

Affiliations

¹ Department of Dentistry, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
² Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada; Department of Pathology and Laboratory Medicine, London Health Sciences Centre, London, Ontario, Canada.
³ 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.
⁴ 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. Electronic address: Cmccord4@uwo.ca.

PMID: 31902664
DOI: 10.1016/j.oooo.2019.09.019

Abstract

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.

MeSH terms

Biomarkers, Tumor
Carcinoma in Situ*
Cyclin-Dependent Kinase Inhibitor p16
Humans
Immunohistochemistry
Ki-67 Antigen
Papillomaviridae*
Papillomavirus Infections*

Substances

Biomarkers, Tumor
Cyclin-Dependent Kinase Inhibitor p16
Ki-67 Antigen