Prediction of survival of HPV16-negative, p16-negative oral cavity cancer patients using a 13-gene signature: A multicenter study using FFPE samples. Oral Oncol 2020 Jan;100:104487
Date
12/14/2019Pubmed ID
31835136Pubmed Central ID
PMC7386199DOI
10.1016/j.oraloncology.2019.104487Scopus ID
2-s2.0-85076314857 (requires institutional sign-in at Scopus site) 6 CitationsAbstract
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.
Author List
Chen C, Lohavanichbutr P, Zhang Y, Houck JR, Upton MP, Abedi-Ardekani B, Agudo A, Ahrens W, Alemany L, Anantharaman D, Conway DI, Futran ND, Holcatova I, Günther K, Hansen BT, Healy CM, Itani D, Kjaerheim K, Monroe MM, Thomson PJ, Witt BL, Nakoneshny S, Peterson LA, Schwartz SM, Zarins KR, Hashibe M, Brennan P, Rozek LS, Wolf G, Dort JC, Wang PMESH terms used to index this publication - Major topics in bold
AdultAged
Aged, 80 and over
Area Under Curve
Biomarkers, Tumor
Carcinoma, Squamous Cell
Cyclin-Dependent Kinase Inhibitor p16
Female
Gene Expression Profiling
Human papillomavirus 16
Humans
Male
Middle Aged
Mouth Neoplasms
Neoplasm Staging
Paraffin Embedding
Sequence Analysis, RNA
Survival Analysis
Tissue Fixation
Young Adult