Prediction of survival of HPV16-negative, p16-negative oral cavity cancer patients using a 13-gene signature: a multicenter study using FFPE samples

Chen, C. et al. (2020) Prediction of survival of HPV16-negative, p16-negative oral cavity cancer patients using a 13-gene signature: a multicenter study using FFPE samples. Oral Oncology, 100, 104487. (doi: 10.1016/j.oraloncology.2019.104487) (PMID:31835136)

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Objectives: To test the performance of an oral cancer prognostic 13-gene signature for the prediction of survival of patients diagnosed with HPV-negative and p16-negative oral cavity cancer. Materials and Methods: Diagnostic formalin-fixed paraffin-embedded oral cavity cancer tumor samples were obtained from the Fred Hutchinson Cancer Research Center/University of Washington, University of Calgary, University of Michigan, University of Utah, and seven ARCAGE study centers coordinated by the International Agency of Research on Cancer. RNA from 638 Human Papillomavirus (HPV)-negative and p16-negative samples was analyzed for the 13 genes using a NanoString assay. Ridge-penalized Cox regressions were applied to samples randomly split into discovery and validation sets to build models and evaluate the performance of the 13-gene signature in predicting 2-year oral cavity cancer-specific survival overall and separately for patients with early and late stage disease. Results: Among AJCC stage I/II patients, including the 13-gene signature in the model resulted in substantial improvement in the prediction of 2-year oral cavity cancer-specific survival. For models containing age and sex with and without the 13-gene signature score, the areas under the Receiver Operating Characteristic Curve (AUC) and partial AUC were 0.700 vs. 0.537 (p < 0.001), and 0.046 vs. 0.018 (p < 0.001), respectively. Improvement in predicting prognosis for AJCC stage III/IV disease also was observed, but to a lesser extent. Conclusions: If confirmed using tumor samples from a larger number of early stage oral cavity cancer patients, the 13-gene signature may inform personalized treatment of early stage HPV-negative and p16-negative oral cavity cancer patients.

Item Type:Articles
Additional Information:This research was supported by a grant from the National Cancer Institute, National Institute of Health [1 R01 CA177736-01A1], the Genomics Shared Resource of the Fred Hutch/University of Washington Cancer Consortium [NIH/NCI P30CA015704], and by institutional funds from the Fred Hutchinson Cancer Research Center. Wang was also supported by NIH grant U24 CA210993. Prior funding supports for the Oralchip study include: NIH R01CA095419, National Research Service Award T32DC00018 from the National Institute on Deafness and Other Communication Disorders, and trans-NIH K12RR023265 Career Development Programs for Clinical Researchers. The contribution of samples and data made by The University of Michigan Head and Neck Specialized Program of Research Excellence was supported by NIH/NCI P50CA097248 and NIH/NIDCD T32 DC005356 and by NIH/NCI P30CA046592 for the use of Rogel Cancer Center Shared Resource: Tissue and Molecular Pathology Core. The contribution made by the Biorepository and Molecular Pathology Resource at Huntsman Cancer Institute at the University of Utah was supported by NIH/NCI P30CA042014.
Glasgow Author(s) Enlighten ID:Conway, Professor David
Authors: Chen, C., Lohavanichbutr, P., Zhang, Y., Houck, J. R., Upton, M. P., Abedi-Ardekani, B., Agudo, A., Ahrens, W., Alemany, L., Anantharaman, D., Conway, D. I., Futran, N. D., Holcatova, I., Günther, K., Hansen, B. T., Healy, C. M., Itani, D., Kjaerheim, K., Monroe, M. M., Thomson, P. J., Witt, B. L., Nakoneshny, S., Peterson, L. A., Schwartz, S. M., Zarins, K. R., Hashibe, M., Brennan, P., Rozek, L. S., Wolf, G., Dort, J. C., and Wang, P.
College/School:College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing > Dental School
Journal Name:Oral Oncology
ISSN (Online):1879-0593
Published Online:10 December 2019
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in Oral Oncology 100:104487
Publisher Policy:Reproduced under a Creative Commons License

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