@article{4dbb56e07a334a9ea48981ae54a71c70,
title = "Nuclear F-actin Cytology in Oral Epithelial Dysplasia and Oral Squamous Cell Carcinoma",
abstract = "Oral cavity cancer has a low 5-y survival rate, but outcomes improve when the disease is detected early. Cytology is a less invasive method to assess oral potentially malignant disorders relative to the gold-standard scalpel biopsy and histopathology. In this report, we aimed to determine the utility of cytological signatures, including nuclear F-actin cell phenotypes, for classifying the entire spectrum of oral epithelial dysplasia and oral squamous cell carcinoma. We enrolled subjects with oral potentially malignant disorders, subjects with previously diagnosed malignant lesions, and healthy volunteers without lesions and obtained brush cytology specimens and matched scalpel biopsies from 486 subjects. Histopathological assessment of the scalpel biopsy specimens classified lesions into 6 categories. Brush cytology specimens were analyzed by machine learning classifiers trained to identify relevant cytological features. Multimodal diagnostic models were developed using cytology results, lesion characteristics, and risk factors. Squamous cells with nuclear F-actin staining were associated with early disease (i.e., lower proportions in benign lesions than in more severe lesions), whereas small round parabasal-like cells and leukocytes were associated with late disease (i.e., higher proportions in severe dysplasia and carcinoma than in less severe lesions). Lesions with the impression of oral lichen planus were unlikely to be either dysplastic or malignant. Cytological features substantially improved upon lesion appearance and risk factors in predicting squamous cell carcinoma. Diagnostic models accurately discriminated early and late disease with AUCs (95% CI) of 0.82 (0.77 to 0.87) and 0.93 (0.88 to 0.97), respectively. The cytological features identified here have the potential to improve screening and surveillance of the entire spectrum of oral potentially malignant disorders in multiple care settings.",
keywords = "actins, artificial intelligence, biomarkers, cell biology, point-of-care testing, single-cell analysis",
author = "McRae, {M. P.} and Kerr, {A. R.} and Janal, {M. N.} and Thornhill, {M. H.} and Redding, {S. W.} and N. Vigneswaran and Kang, {S. K.} and R. Niederman and Christodoulides, {N. J.} and Trochesset, {D. A.} and C. Murdoch and I. Dapkins and J. Bouquot and Modak, {S. S.} and Simmons, {G. W.} and McDevitt, {J. T.}",
note = "Funding Information: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: M.P. McRae has served as a paid consultant for SensoDx and has a provisional patent pending. G.W. Simmons has patents US10060937B2 and US7781226B2 issued. D.A. Trochesset has received grants from the New York University College of Dentistry for work performed as part of the current study. M.H. Thornhill has received National Institutes of Health grant 1RC2DE020785-01 for work performed as part of the current study. S.W. Redding has patent US9535068B2 issued. S.K. Kang has received royalties from Wolters Kluwer and honoraria from the American Journal of Roentgenology for work performed outside of the current study. J.T. McDevitt has received grants from the National Institutes of Health for work performed as part of the current study (grants 1RC2DE020785-01, 4R44DE025798-02, and R01DE024392) and has a provisional patent pending. In addition, he has ownership positions and equity interest in both SensoDx II LLC and OraLiva, Inc. All other authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article. Funding Information: The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Research reported in this publication was supported by the National Institute of Dental and Craniofacial Research Division of the National Institutes of Health (1RC2DE020785-01, 4R44DE 025798-02, and R01DE024392) with a portion of the funding being derived from Renaissance Health Service Corporation and Delta Dental of Michigan. Rho Inc., a contract research organization (Chapel Hill, NC, USA), provided statistical, regulatory, data management and clinical monitoring support, as well as operational management. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Funding Information: The authors thank the University of Texas Health Science Center at San Antonio (UTHSCSA) (Stephanie Rowan, Chih-Ko Yeh, Stan McGuff, Frank Miller), University of Texas Health Science Center at Houston (UTHSCH) (Nagi Demian, Etan Weinstock, Nancy Bass), New York University/Bluestone Center for Clinical Research (Joan Phelan, Patricia Corby, Ismael Khouly), Sheffield Teaching Hospitals NHS Foundation Trust, and the University of Sheffield (Paul Speight, Christine Freeman, Anne Hegarty, Katy D?Apice) for assistance in obtaining and pathological evaluation of clinical samples. The authors also thank Rho, Inc. (Chapel Hill, North Carolina) (Julie Vick) for assisting with patient data management and (Robert James) for statistical and data analysis support. Pathologists who performed scoring of histologic sections include Paul M. Speight, PhD, BDS, FDSRCPS, FDSRCS (Eng), FDSRCS (Edin), FRCPath (Academic Unit of Oral & Maxillofacial Pathology, University of Sheffield School of Clinical Dentistry, Sheffield, UK), Joan Phelan, DDS (New York University College of Dentistry, Department of Oral and Maxillofacial Pathology, Radiology & Medicine, New York, NY, USA), Nadarajah Vigneswaran, DMD, Dr Med Dent (The University of Texas Health Science Center at Houston, Department of Diagnostic and Biomedical Sciences, Houston, TX, USA), H. Stan McGuff, DDS (The University of Texas Health Science Center at San Antonio, Department of Pathology, San Antonio, TX, USA), and Jerry Bouquot, DDS, MSD (The University of Texas Health Science Center at Houston, Department of Diagnostic and Biomedical Sciences, Houston, TX, USA). Finally, the authors thank Shannon Weigum, Pierre Floriano, and Timothy J. Abram for early contributions to the project, including assay development and database organization. The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Research reported in this publication was supported by the National Institute of Dental and Craniofacial Research Division of the National Institutes of Health (1RC2DE020785-01, 4R44DE 025798-02, and R01DE024392) with a portion of the funding being derived from Renaissance Health Service Corporation and Delta Dental of Michigan. Rho Inc., a contract research organization (Chapel Hill, NC, USA), provided statistical, regulatory, data management and clinical monitoring support, as well as operational management. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Publisher Copyright: {\textcopyright} International & American Associations for Dental Research 2020.",
year = "2021",
month = may,
doi = "10.1177/0022034520973162",
language = "English (US)",
volume = "100",
pages = "479--486",
journal = "Journal of dental research",
issn = "0022-0345",
publisher = "SAGE Publications Inc.",
number = "5",
}