Identification of Malignancy-Associated Changes in Histologically Normal Tumor-Adjacent Epithelium of Patients with HPV-Positive Oropharyngeal Cancer
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 d...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2018-01-01
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| Series: | Analytical Cellular Pathology |
| Online Access: | http://dx.doi.org/10.1155/2018/1607814 |
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| _version_ | 1832553729220411392 |
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| author | James Jabalee Anita Carraro Tony Ng Eitan Prisman Cathie Garnis Martial Guillaud |
| author_facet | James Jabalee Anita Carraro Tony Ng Eitan Prisman Cathie Garnis Martial Guillaud |
| author_sort | James Jabalee |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-1aaffa20c0b94410a522ca8c5b597686 |
| institution | Kabale University |
| issn | 2210-7177 2210-7185 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Analytical Cellular Pathology |
| spelling | doaj-art-1aaffa20c0b94410a522ca8c5b5976862025-02-03T05:53:16ZengWileyAnalytical Cellular Pathology2210-71772210-71852018-01-01201810.1155/2018/16078141607814Identification of Malignancy-Associated Changes in Histologically Normal Tumor-Adjacent Epithelium of Patients with HPV-Positive Oropharyngeal CancerJames Jabalee0Anita Carraro1Tony Ng2Eitan Prisman3Cathie Garnis4Martial Guillaud5British Columbia Cancer Research Centre, Department of Integrative Oncology, Vancouver, BC, CanadaBritish Columbia Cancer Research Centre, Department of Integrative Oncology, Vancouver, BC, CanadaDepartment of Pathology, Vancouver General Hospital and University of British Columbia, Vancouver, BC, CanadaVancouver General Hospital, Division of Otolaryngology-Head and Neck Surgery, Vancouver, BC, CanadaBritish Columbia Cancer Research Centre, Department of Integrative Oncology, Vancouver, BC, CanadaBritish Columbia Cancer Research Centre, Department of Integrative Oncology, Vancouver, BC, CanadaThe 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.http://dx.doi.org/10.1155/2018/1607814 |
| spellingShingle | James Jabalee Anita Carraro Tony Ng Eitan Prisman Cathie Garnis Martial Guillaud Identification of Malignancy-Associated Changes in Histologically Normal Tumor-Adjacent Epithelium of Patients with HPV-Positive Oropharyngeal Cancer Analytical Cellular Pathology |
| title | Identification of Malignancy-Associated Changes in Histologically Normal Tumor-Adjacent Epithelium of Patients with HPV-Positive Oropharyngeal Cancer |
| title_full | Identification of Malignancy-Associated Changes in Histologically Normal Tumor-Adjacent Epithelium of Patients with HPV-Positive Oropharyngeal Cancer |
| title_fullStr | Identification of Malignancy-Associated Changes in Histologically Normal Tumor-Adjacent Epithelium of Patients with HPV-Positive Oropharyngeal Cancer |
| title_full_unstemmed | Identification of Malignancy-Associated Changes in Histologically Normal Tumor-Adjacent Epithelium of Patients with HPV-Positive Oropharyngeal Cancer |
| title_short | Identification of Malignancy-Associated Changes in Histologically Normal Tumor-Adjacent Epithelium of Patients with HPV-Positive Oropharyngeal Cancer |
| title_sort | identification of malignancy associated changes in histologically normal tumor adjacent epithelium of patients with hpv positive oropharyngeal cancer |
| url | http://dx.doi.org/10.1155/2018/1607814 |
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