Background In an attempt to improve the prognosis of patients with head and neck cancer, it could be necessary to identify biomarkers in homogeneous subgroups of patients with head and neck cancer. Methods We explored the necessity of human papillomavirus (HPV) status-specific biomarkers in patients with head and neck cancer and identified an HPV status-specific gene set. The identified gene set was validated with the external microarray datasets. For this purpose, we used 4 microarray datasets obtained from a public database. One dataset was used for identifying the HPV status specific gene set, and the other datasets were used for validation. Results The identified gene set for distinguishing head and neck cancer from head and neck normal, did not accurately discriminate the HPV specific patients with head and neck cancer from the head and neck normal group. Also, it was demonstrated that some HPV-positive (HPV+) head and neck cancer-specific genes may not be significant in HPV-negative (HPV-) head and neck cancer patients. The identified HPV specific gene sets showed good performance in validation datasets. The HPV+ head and neck cancer-specific gene set included various metabolism-related pathways, and the HPV- head and neck cancer-specific gene set included several pathways; fibroblast, collagen degradation, actin-binding, and actin cytoskeleton. Conclusion The identification of HPV status-specific significant gene set was necessary. It is expected that HPV status-specific biomarkers can be helpful in deciding therapeutic methods for patients with head and neck cancer, after biological validation and large prospective trials.
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