Abstract
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.
Highlights
Oropharyngeal cancers (OPCs), which include malignancies of the tonsils, posterior pharyngeal wall, soft palate, and tongue base, have undergone a dramatic epidemiological shift
To avoid the drawbacks of chemoradiation therapy (CRT), transoral robotic surgery (TORS), in which the tumor is resected through the mouth, is currently being investigated as an alternative treatment option [6]
The distribution of Large-Scale DNA Organization (LDO) scores of adjacent normal nuclei is statistically significantly different from both the contralateral normal and tumor for each of the nine patients (ANOVA with Tukey’s post hoc honestly significant difference test, p < 0 001). These results strongly suggest the presence of Malignancy-associated changes (MACs) in histologically normal tumor-adjacent epithelial cell nuclei
Summary
Oropharyngeal cancers (OPCs), which include malignancies of the tonsils, posterior pharyngeal wall, soft palate, and tongue base, have undergone a dramatic epidemiological shift. While the rate of tobacco and alcohol-related head and neck cancers is declining in North America, the incidence of HPV-positive OPC (HPV+ OPC) has been steadily rising since the early 1980s and is especially prevalent among young individuals (
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