PMID- 36066461 OWN - NLM STAT- MEDLINE DCOM- 20221017 LR - 20230426 IS - 1097-0142 (Electronic) IS - 0008-543X (Print) IS - 0008-543X (Linking) VI - 128 IP - 21 DP - 2022 Nov 1 TI - Image analysis reveals differences in tumor multinucleations in Black and White patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma. PG - 3831-3842 LID - 10.1002/cncr.34446 [doi] 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, 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. CI - (c) 2022 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society. FAU - Koyuncu, Can F AU - Koyuncu CF AUID- ORCID: 0000-0001-5990-2226 AD - Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia, USA. AD - Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, Ohio, USA. FAU - Nag, Reetoja AU - Nag R AUID- ORCID: 0000-0001-8707-3840 AD - Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia, USA. FAU - Lu, Cheng AU - Lu C AD - Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia, USA. FAU - Corredor, German AU - Corredor G AUID- ORCID: 0000-0003-3002-0937 AD - Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia, USA. AD - Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, Ohio, USA. FAU - Viswanathan, Vidya S AU - Viswanathan VS AD - Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia, USA. FAU - Sandulache, Vlad C AU - Sandulache VC AD - Baylor College of Medicine, Houston, Texas, USA. AD - Otolaryngology-Head and Neck Surgery, Operative Care Line, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA. FAU - Fu, Pingfu AU - Fu P AD - Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, Ohio, USA. FAU - Yang, Kailin AU - Yang K AD - Cleveland Clinic Foundation, Cleveland, Ohio, USA. FAU - Pan, Quintin AU - Pan Q AD - Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, Ohio, USA. FAU - Zhang, Zelin AU - Zhang Z AD - Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia, USA. FAU - Xu, Jun AU - Xu J AD - Nanjing University of Information Science and Technology, Nanjing, China. FAU - Chute, Deborah J AU - Chute DJ AD - Cleveland Clinic Foundation, Cleveland, Ohio, USA. FAU - Thorstad, Wade L AU - Thorstad WL AD - Washington University in St. Louis, St. Louis, Missouri, USA. FAU - Faraji, Farhoud AU - Faraji F AUID- ORCID: 0000-0001-5078-813X AD - University of California San Diego, San Diego, California, USA. FAU - Bishop, Justin A AU - Bishop JA AD - University of Texas Southwestern Medical Center, Dallas, Texas, USA. FAU - Mehrad, Mitra AU - Mehrad M AD - Vanderbilt University Medical Center, Nashville, Tennessee, USA. FAU - Castro, Patricia D AU - Castro PD AD - Baylor College of Medicine, Houston, Texas, USA. FAU - Sikora, Andrew G AU - Sikora AG AD - Baylor College of Medicine, Houston, Texas, USA. FAU - Thompson, Lester D R AU - Thompson LDR AD - Southern California Permanente Medical Group, Pasadena, California, USA. FAU - Chernock, Rebecca D AU - Chernock RD AD - Washington University in St. Louis, St. Louis, Missouri, USA. FAU - Lang Kuhs, Krystle A AU - Lang Kuhs KA AD - Vanderbilt University Medical Center, Nashville, Tennessee, USA. FAU - Wasman, Jay K AU - Wasman JK AD - School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA. FAU - Luo, Jingqin R AU - Luo JR AD - Washington University in St. Louis, St. Louis, Missouri, USA. FAU - Adelstein, David J AU - Adelstein DJ AD - Cleveland Clinic Foundation, Cleveland, Ohio, USA. FAU - Koyfman, Shlomo A AU - Koyfman SA AD - Cleveland Clinic Foundation, Cleveland, Ohio, USA. FAU - Lewis, James S Jr AU - Lewis JS Jr AD - Vanderbilt University Medical Center, Nashville, Tennessee, USA. FAU - Madabhushi, Anant AU - Madabhushi A AD - Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia, USA. AD - Atlanta Veterans Administration Medical Center, Atlanta, Georgia, USA. AD - Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, Ohio, USA. LA - eng GR - CX001953/VA/VA/United States GR - C06 RR012463/RR/NCRR NIH HHS/United States GR - U24 CA199374/CA/NCI NIH HHS/United States GR - U01 CA239055/CA/NCI NIH HHS/United States GR - R01 HL158071/HL/NHLBI NIH HHS/United States GR - IK2 CX001953/CX/CSRD VA/United States GR - R01 CA268287/CA/NCI NIH HHS/United States GR - R01 CA249992/CA/NCI NIH HHS/United States GR - R01 HL151277/HL/NHLBI NIH HHS/United States GR - R01 CA220581/CA/NCI NIH HHS/United States GR - R01 CA216579/CA/NCI NIH HHS/United States GR - R01 CA268207/CA/NCI NIH HHS/United States GR - R01 CA202752/CA/NCI NIH HHS/United States GR - R01 CA208236/CA/NCI NIH HHS/United States GR - U01 CA248226/CA/NCI NIH HHS/United States GR - I01 BX004121/BX/BLRD VA/United States GR - R43 EB028736/EB/NIBIB NIH HHS/United States GR - P30 CA091842/CA/NCI NIH HHS/United States GR - U01 CA269181/CA/NCI NIH HHS/United States GR - K07 CA218247/CA/NCI NIH HHS/United States GR - T32 DC000028/DC/NIDCD NIH HHS/United States GR - R01 CA257612/CA/NCI NIH HHS/United States GR - U54 CA254566/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20220906 PL - United States TA - Cancer JT - Cancer JID - 0374236 RN - 0 (Biomarkers) RN - TDQ283MPCW (Eosine Yellowish-(YS)) RN - YKM8PY2Z55 (Hematoxylin) SB - IM MH - *Alphapapillomavirus MH - Biomarkers MH - *Carcinoma, Squamous Cell/pathology MH - Eosine Yellowish-(YS) MH - *Head and Neck Neoplasms/complications MH - Hematoxylin MH - Humans MH - *Oropharyngeal Neoplasms MH - Papillomaviridae MH - *Papillomavirus Infections MH - Prognosis MH - Retrospective Studies MH - Squamous Cell Carcinoma of Head and Neck/complications PMC - PMC9782693 MID - NIHMS1837107 OTO - NOTNLM OT - Black OT - HPV OT - MuNI OT - OPSCC OT - White OT - image analysis COIS- Rebecca D. Chernock reports funding from Caris Life Sciences and Merck. Deborah J. Chute reports book royalties. German 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. EDAT- 2022/09/07 06:00 MHDA- 2022/10/18 06:00 PMCR- 2023/01/08 CRDT- 2022/09/06 10:33 PHST- 2022/05/17 00:00 [revised] PHST- 2022/03/21 00:00 [received] PHST- 2022/06/28 00:00 [accepted] PHST- 2022/09/07 06:00 [pubmed] PHST- 2022/10/18 06:00 [medline] PHST- 2022/09/06 10:33 [entrez] PHST- 2023/01/08 00:00 [pmc-release] AID - CNCR34446 [pii] AID - 10.1002/cncr.34446 [doi] PST - ppublish SO - Cancer. 2022 Nov 1;128(21):3831-3842. doi: 10.1002/cncr.34446. Epub 2022 Sep 6.