Computerized tumor multinucleation index (MuNI) is prognostic in p16+ oropharyngeal carcinoma

Can F. Koyuncu, Cheng Lu, Kaustav Bera, Zelin Zhang, Jun Xu, Paula Toro, German Corredor, Deborah Chute, Pingfu Fu, Wade L. Thorstad, F. Faraji, Justin A. Bishop, Mitra Mehrad, Patricia D. Castro, Andrew G. Sikora, Lester D.R. Thompson, R. D. Chernock, Krystle A. Lang Kuhs, Jingqin Luo, Vlad SandulacheDavid J. Adelstein, Shlomo Koyfman, James S. Lewis, Anant Madabhushi

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


BACKGROUND. Patients with p16+ oropharyngeal squamous cell carcinoma (OPSCC) are potentially cured with definitive treatment. However, there are currently no reliable biomarkers of treatment failure for p16+ OPSCC. Pathologist-based visual assessment of tumor cell multinucleation (MN) has been shown to be independently prognostic of disease-free survival (DFS) in p16+ OPSCC. However, its quantification is time intensive, subjective, and at risk of interobserver variability. METHODS. We present a deep-learning-based metric, the multinucleation index (MuNI), for prognostication in p16+ OPSCC. This approach quantifies tumor MN from digitally scanned H&E-stained slides. Representative H&E-stained whole-slide images from 1094 patients with previously untreated p16+ OPSCC were acquired from 6 institutions for optimization and validation of the MuNI. RESULTS. The MuNI was prognostic for DFS, overall survival (OS), or distant metastasis-free survival (DMFS) in p16+ OPSCC, with HRs of 1.78 (95% CI: 1.37-2.30), 1.94 (1.44-2.60), and 1.88 (1.43-2.47), respectively, independent of age, smoking status, treatment type, or tumor and lymph node (T/N) categories in multivariable analyses. The MuNI was also prognostic for DFS, OS, and DMFS in patients with stage I and stage III OPSCC, separately. CONCLUSION. MuNI holds promise as a low-cost, tissue-nondestructive, H&E stain-based digital biomarker test for counseling, treatment, and surveillance of patients with p16+ OPSCC. These data support further confirmation of the MuNI in prospective trials.

Original languageEnglish
Article numbere145488
JournalJournal of Clinical Investigation
Issue number8
StatePublished - Apr 15 2021


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