Image analysis reveals differences in tumor multinucleations in Black and White patients with human papillomavirus‐associated oropharyngeal squamous cell carcinoma
Can Koyuncu, Reetoja Nag, Cheng Lu, Germán Corredor, Vidya Sankar Viswanathan, Vlad C. Sandulache, Pingfu Fu, Kailin Yang, Quintin Pan, Zelin Zhang, Jun Xu, Deborah J. Chute, Wade L. Thorstad, Farhoud Faraji, Justin A. Bishop, Mitra Mehrad, Patricia Castro, Andrew G. Sikora, Lester D.�R. Thompson, Rebecca D. Chernock, Krystle A. Lang Kuhs, Jay Wasman, Jingqin Luo, David J. Adelstein, Shlomo A. Koyfman, James S. Lewis, Anant Madabhushi
Abstract
Background Understanding biological differences between different racial groups of human papillomavirus (HPV)‐associated oropharyngeal squamous cell carcinoma (OPSCC) patients, who have differences in terms of incidence, survival, and tumor morphology, can facilitate accurate prognostic biomarkers, which can help develop personalized treatment strategies. Methods This study evaluated whether there were morphologic differences between HPV‐associated tumors from Black and White patients in terms of multinucleation index (MuNI), an image analysis‐derived metric that measures density of multinucleated tumor cells within epithelial regions on hematoxylin–eosin images and previously has been prognostic in HPV‐associated OPSCC patients. In this study, the authors specifically evaluated whether the same MuNI cutoff that was prognostic of overall survival (OS) and disease‐free survival in their previous study, T TR , is valid for Black and White patients, separately. We also evaluated population‐specific cutoffs, T B for Blacks and T W for Whites, for risk stratification. Results MuNI was statistically significantly different between Black (mean, 3.88e–4; median, 3.67e–04) and White patients (mean, 3.36e–04; median, 2.99e–04), with p = .0078. Using T TR , MuNI was prognostic of OS in the entire population with hazard ratio (HR) of 1.71 ( p = .002; 95% confidence interval [CI], 1.21–2.43) and in White patients with HR of 1.72 ( p = .005; 95% CI, 1.18–2.51). Population‐specific cutoff, T W , yielded improved HR of 1.77 ( p = .003; 95% CI, 1.21–2.58) for White patients, whereas T B did not improve risk‐stratification in Black patients with HR of 0.6 ( p = .3; HR, 0.6; 95% CI, 0.2–1.80). Conclusions Histological difference between White and Black patient tumors in terms of multinucleated tumor cells suggests the need for considering population‐specific prognostic biomarkers for personalized risk stratification strategies for HPV‐associated OPSCC patients.