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Analytical Cellular Pathology
Volume 2018, Article ID 1607814, 9 pages
Research Article

Identification of Malignancy-Associated Changes in Histologically Normal Tumor-Adjacent Epithelium of Patients with HPV-Positive Oropharyngeal Cancer

1British Columbia Cancer Research Centre, Department of Integrative Oncology, Vancouver, BC, Canada
2Department of Pathology, Vancouver General Hospital and University of British Columbia, Vancouver, BC, Canada
3Vancouver General Hospital, Division of Otolaryngology-Head and Neck Surgery, Vancouver, BC, Canada
4University of British Columbia, Vancouver, BC, Canada

Correspondence should be addressed to Martial Guillaud; ac.crccb@ualliugm

Received 29 November 2017; Revised 8 January 2018; Accepted 11 January 2018; Published 11 March 2018

Academic Editor: Anant Madabhushi

Copyright © 2018 James Jabalee et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The incidence of HPV-positive oropharyngeal cancer (HPV+ OPC) is increasing, thus presenting new challenges for disease detection and management. Noninvasive methods involving brush biopsies of diseased tissues were recently reported as insufficient for tumor detection in HPV+ OPC patients, likely due to differences between the site of tumor initiation at the base of involuted crypts and the site of brush biopsy at the crypt surface. We hypothesized that histologically normal surface epithelial cells in the oropharynx contain changes in nuclear morphology that arise due to tumor proximity. We analyzed the nuclear phenotype of matched tumor, tumor-adjacent normal, and contralateral normal tissues from biopsies of nine HPV+ OPC patients. Measurements of 89 nuclear features were used to train a random forest-based classifier to discriminate between normal and tumor nuclei. We then extracted voting scores from the trained classifier, which classify nuclei on a continuous scale from zero (“normal-like”) to one (“tumor-like”). In each case, the average score of the adjacent normal nuclei was intermediate between the tumor and contralateral normal nuclei. These results provide evidence for the existence of phenotypic changes in histologically normal, tumor-adjacent surface epithelial cells, which could be used as brush biopsy-based biomarkers for HPV+ OPC detection.