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, TTR, is valid for Black and White patients, separately. We also evaluated population-specific cutoffs, TB for Blacks and TW 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 TTR, 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, TW, yielded improved HR of 1.77 (p =.003; 95% CI, 1.21–2.58) for White patients, whereas TB 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.
| Original language | English |
|---|---|
| Pages (from-to) | 3831-3842 |
| Number of pages | 12 |
| Journal | Cancer |
| Volume | 128 |
| Issue number | 21 |
| DOIs | |
| State | Published - Nov 1 2022 |
Keywords
- Black
- HPV
- MuNI
- OPSCC
- White
- image analysis
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In: Cancer, Vol. 128, No. 21, 01.11.2022, p. 3831-3842.
Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - Image analysis reveals differences in tumor multinucleations in Black and White patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma
AU - Koyuncu, Can F.
AU - Nag, Reetoja
AU - Lu, Cheng
AU - Corredor, Germán
AU - Viswanathan, Vidya S.
AU - Sandulache, Vlad C.
AU - Fu, Pingfu
AU - Yang, Kailin
AU - Pan, Quintin
AU - Zhang, Zelin
AU - Xu, Jun
AU - Chute, Deborah J.
AU - Thorstad, Wade L.
AU - Faraji, Farhoud
AU - Bishop, Justin A.
AU - Mehrad, Mitra
AU - Castro, Patricia D.
AU - Sikora, Andrew G.
AU - Thompson, Lester D.R.
AU - Chernock, Rebecca D.
AU - Lang Kuhs, Krystle A.
AU - Wasman, Jay K.
AU - Luo, Jingqin R.
AU - Adelstein, David J.
AU - Koyfman, Shlomo A.
AU - Lewis, James S.
AU - Madabhushi, Anant
N1 - Funding Information: Rebecca D. Chernock reports funding from Caris Life Sciences and Merck. Deborah J. Chute reports book royalties. Germán Corredor reports a grant from the US Department of Defense. Farhoud Faraji reports funding from the National Institute on Deafness and Other Communication Disorders and Stand Up To Cancer. James S. Lewis Jr reports a grant from National Institutes of Health and payment as an expert witness from Shook, Hardy, and Bacon. Jingqin R. Luo reports a grant from National Institutes of Health. Anant Madabhushi reports grants from AstraZeneca, Boehringer Ingelheim, and Bristol‐Myers Squibb; consulting fees from Aiforia, Caris, and SimBioSys; participation as a fiduciary officer with Picture Health; and stock options with Elucid Bioimaging. Andrew G. Sikora reports consulting fees from F. Hoffmann‐La Roche. Lester D.R. Thompson reports funding from Elsevier. Jun Xu reports a grant from the National Natural Science Foundation of China. Kailin Yang reports grants from the Conquer Cancer Foundation, the National Cancer Institute, and RSNA Research and Education Foundation; and travel funding from Case Comprehensive Cancer Center and Case Western Reserve University. The other authors made no disclosures. Funding Information: Research reported in this publication was supported by the National Cancer Institute under award numbers R01CA268207‐01A1, R01CA249992‐01A1, R01CA202752‐01A1, R01CA208236‐01A1, R01CA216579‐01A1, R01CA220581‐01A1, R01CA257612‐01A1, 1U01CA239055‐01, 1U01CA248226‐01, 1U54CA254566‐01, National Heart, Lung and Blood Institute 1R01HL15127701A1, R01HL15807101A1, National Institute of Biomedical Imaging and Bioengineering 1R43EB028736‐01, National Center for Research Resources under award number 1 C06 RR12463‐01, VA Merit Review Award IBX004121A from the United States Department of Veterans Affairs Biomedical Laboratory Research and Development Servicethe Office of the Assistant Secretary of Defense for Health Affairs, through the Breast Cancer Research Program (W81XWH‐19‐1‐0668), the Prostate Cancer Research Program (W81XWH‐20‐1‐0851), the Lung Cancer Research Program (W81XWH‐18‐1‐0440, W81XWH‐20‐1‐0595), the Peer Reviewed Cancer Research Program (W81XWH‐18‐1‐0404, W81XWH‐21‐1‐0345, W81XWH‐21‐1‐0160, and W81XWH‐22‐1‐0236), the Kidney Precision Medicine Project (KPMP) Glue Grant and sponsored research agreements from Bristol Myers‐Squibb, Boehringer‐Ingelheim, Eli‐Lilly and Astrazeneca. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health, the U.S. Department of Veterans Affairs, the Department of Defense, or the United States Government. Funding Information: This study was reviewed and approved by the institutional review boards of Washington University in St. Louis, Missouri, USA; Johns Hopkins University in Baltimore, Maryland, USA; the Cleveland Clinic in Cleveland, Ohio, USA; Case Western Reserve University in Cleveland, Ohio, USA; Cleveland University Hospital Seidman Cancer Center in Cleveland, Ohio, USA; the Southern California Permanente Medical Group in Los Angeles, California, USA; Vanderbilt University Medical Center in Nashville, Tennessee, USA; and the Michael E. DeBakey VA Medical Center in Houston, Texas, USA. This study was supported by the National Cancer Institute (R01CA249992-01A1, R01CA202752-01A1, R01CA208236-01A1, R01CA216579-01A1, R01CA220581-01A1, R01CA257612-01A1, 1U01CA239055-01, 1U01CA248226-01, and 1U54CA254566-01), National Heart, Lung and Blood Institute (1R01HL15127701A1 and R01HL15807101A1), National Institute of Biomedical Imaging and Bioengineering (1R43EB028736-01), National Center for Research Resources (1 C06 RR12463-01), a VA Merit Review Award (IBX004121A) from the US Department of Veterans Affairs Biomedical Laboratory Research and Development Service, the Office of the Assistant Secretary of Defense for Health Affairs, through the Breast Cancer Research Program (W81XWH-19-1-0668), the Prostate Cancer Research Program (W81XWH-15-1-0558 and W81XWH-20-1-0851), the Lung Cancer Research Program (W81XWH-18-1-0440 and W81XWH-20-1-0595), the Peer Reviewed Cancer Research Program (W81XWH-18-1-0404 and W81XWH-21-1-0345), the Kidney Precision Medicine Project (KPMP) Glue Grant, and sponsored research agreements from Bristol Myers-Squibb, Boehringer-Ingelheim, and AstraZeneca. Vlad C. Sandulache is supported by Career Development Award (IK2 CX001953) from the US Department of Veterans Affairs Clinical Sciences R&D Service. Farhoud Faraji is supported by Stand Up to Cancer (308268-00001) Precision Therapy for Fanconi Anemia and HPV-related Head & Neck Cancer and National Institutes of Health (T32DC000028). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health, the US Department of Veterans Affairs, the Department of Defense, or the US Government. Funding Information: This study was reviewed and approved by the institutional review boards of Washington University in St. Louis, Missouri, USA; Johns Hopkins University in Baltimore, Maryland, USA; the Cleveland Clinic in Cleveland, Ohio, USA; Case Western Reserve University in Cleveland, Ohio, USA; Cleveland University Hospital Seidman Cancer Center in Cleveland, Ohio, USA; the Southern California Permanente Medical Group in Los Angeles, California, USA; Vanderbilt University Medical Center in Nashville, Tennessee, USA; and the Michael E. DeBakey VA Medical Center in Houston, Texas, USA. This study was supported by the National Cancer Institute (R01CA249992‐01A1, R01CA202752‐01A1, R01CA208236‐01A1, R01CA216579‐01A1, R01CA220581‐01A1, R01CA257612‐01A1, 1U01CA239055‐01, 1U01CA248226‐01, and 1U54CA254566‐01), National Heart, Lung and Blood Institute (1R01HL15127701A1 and R01HL15807101A1), National Institute of Biomedical Imaging and Bioengineering (1R43EB028736‐01), National Center for Research Resources (1 C06 RR12463‐01), a VA Merit Review Award (IBX004121A) from the US Department of Veterans Affairs Biomedical Laboratory Research and Development Service, the Office of the Assistant Secretary of Defense for Health Affairs, through the Breast Cancer Research Program (W81XWH‐19‐1‐0668), the Prostate Cancer Research Program (W81XWH‐15‐1‐0558 and W81XWH‐20‐1‐0851), the Lung Cancer Research Program (W81XWH‐18‐1‐0440 and W81XWH‐20‐1‐0595), the Peer Reviewed Cancer Research Program (W81XWH‐18‐1‐0404 and W81XWH‐21‐1‐0345), the Kidney Precision Medicine Project (KPMP) Glue Grant, and sponsored research agreements from Bristol Myers‐Squibb, Boehringer‐Ingelheim, and AstraZeneca. Vlad C. Sandulache is supported by Career Development Award (IK2 CX001953) from the US Department of Veterans Affairs Clinical Sciences R&D Service. Farhoud Faraji is supported by Stand Up to Cancer (308268‐00001) Precision Therapy for Fanconi Anemia and HPV‐related Head & Neck Cancer and National Institutes of Health (T32DC000028). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health, the US Department of Veterans Affairs, the Department of Defense, or the US Government. Publisher Copyright: © 2022 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.
PY - 2022/11/1
Y1 - 2022/11/1
N2 - 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, TTR, is valid for Black and White patients, separately. We also evaluated population-specific cutoffs, TB for Blacks and TW 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 TTR, 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, TW, yielded improved HR of 1.77 (p =.003; 95% CI, 1.21–2.58) for White patients, whereas TB 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.
AB - 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, TTR, is valid for Black and White patients, separately. We also evaluated population-specific cutoffs, TB for Blacks and TW 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 TTR, 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, TW, yielded improved HR of 1.77 (p =.003; 95% CI, 1.21–2.58) for White patients, whereas TB 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.
KW - Black
KW - HPV
KW - MuNI
KW - OPSCC
KW - White
KW - image analysis
UR - http://www.scopus.com/inward/record.url?scp=85138273581&partnerID=8YFLogxK
U2 - 10.1002/cncr.34446
DO - 10.1002/cncr.34446
M3 - Article
C2 - 36066461
AN - SCOPUS:85138273581
SN - 0008-543X
VL - 128
SP - 3831
EP - 3842
JO - Cancer
JF - Cancer
IS - 21
ER -