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Tumour Cell Anaplasia and Multinucleation as Prognosticators in Oropharyngeal Squamous Cell Carcinoma.

ABSTRACT: Human papilloma virus (HPV)-positive oropharyngeal squamous cell carcinomas (OPSCC) tend to have good outcomes, however a subset does not share this favourable prognosis. The aim of this paper is to investigate the utility of tumour cell anaplasia and multinucleation as prognostic markers in oropharyngeal squamous cell carcinoma. Retrospective review of 104 patients with OPSCC or squamous cell carcinoma of unknown primary site (SCCUP) who underwent primary resection and/or lymph node dissection. Slides of both primary and nodal metastatic disease were assessed for the presence of anaplasia and multinucleation. 53 patients were HPV-positive. Anaplasia was more frequent in males (p?=?0.005), smokers (p?=?0.003), and HPV-negative disease (p?=?0.04). HPV status and >?10 pack-year smoking history were independent predictors of recurrence-free survival (RFS) and disease-specific survival (DSS). Neither anaplasia, nor multinucleation, at the primary site or in cervical metastases, had any significant impact on RFS or DSS. We did not find either anaplasia or multinucleation to have any significant prognostic impact in OPSCC. However, given the small number of adverse events in the HPV-positive cohort, we may have lacked sufficient power to detect significance in what was the subgroup of primary interest. Our study highlights the challenge of identifying markers of poor prognosis in HPV-positive OPSCC.

SUBMITTER: Molony P

PROVIDER: S-EPMC7413948 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Tumour Cell Anaplasia and Multinucleation as Prognosticators in Oropharyngeal Squamous Cell Carcinoma.

Molony Peter P Werner Reiltin R Martin Cara C Callanan Deirdre D Sheahan Patrick P Heffron Cynthia C Feeley Linda L

Head and neck pathology 20190924 3

Human papilloma virus (HPV)-positive oropharyngeal squamous cell carcinomas (OPSCC) tend to have good outcomes, however a subset does not share this favourable prognosis. The aim of this paper is to investigate the utility of tumour cell anaplasia and multinucleation as prognostic markers in oropharyngeal squamous cell carcinoma. Retrospective review of 104 patients with OPSCC or squamous cell carcinoma of unknown primary site (SCCUP) who underwent primary resection and/or lymph node dissection. ...[more]

PMID: 31552619

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Project description:BACKGROUNDPatients 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.METHODSWe 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.RESULTSThe 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.CONCLUSIONMuNI 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.FUNDINGNational Cancer Institute (NCI), NIH; National Institute for Biomedical Imaging and Bioengineering, NIH; National Center for Research Resources, NIH; VA Merit Review Award from the US Department of VA Biomedical Laboratory Research and Development Service; US Department of Defense (DOD) Breast Cancer Research Program Breakthrough Level 1 Award; DOD Prostate Cancer Idea Development Award; DOD Lung Cancer Investigator-Initiated Translational Research Award; DOD Peer-Reviewed Cancer Research Program; Ohio Third Frontier Technology Validation Fund; Wallace H. Coulter Foundation Program in the Department of Biomedical Engineering; Clinical and Translational Science Award (CTSA) program, Case Western Reserve University; NCI Cancer Center Support Grant, NIH; Career Development Award from the US Department of VA Clinical Sciences Research and Development Program; Dan L. Duncan Comprehensive Cancer Center Support Grant, NIH; and Computational Genomic Epidemiology of Cancer Program, Case Comprehensive Cancer Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH, the US Department of VA, the DOD, or the US Government.

Dataset Information

Tumour Cell Anaplasia and Multinucleation as Prognosticators in Oropharyngeal Squamous Cell Carcinoma.

Publications

Tumour Cell Anaplasia and Multinucleation as Prognosticators in Oropharyngeal Squamous Cell Carcinoma.

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