This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Slebos, R. J.C. Articles by Chung, C. H. Search for Related Content PubMed PubMed Citation Articles by Slebos, R. J.C. Articles by Chung, C. H.

Gene Expression Differences Associated with Human Papillomavirus Status in Head and Neck Squamous Cell Carcinoma

Authors' Affiliations: Departments of ¹ Cancer Biology, ² Otolaryngology, ³ Pathology, ⁴ Biostatistics, ⁵ Radiation Oncology, and ⁶ Biomedical Informatics; Divisions of ⁷ Genetic Medicine and ⁸ Hematology/Oncology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee

Requests for reprints: Christine H. Chung, Division of Hematology/Oncology, Department of Medicine, Vanderbilt University School of Medicine, 2220 Pierce Avenue, 777 Preston Research Building, Nashville, TN 37232-6307. Phone: 615-322-4967; Fax: 615-343-7602; E-mail: Christine.Chung{at}Vanderbilt.edu.

Human papillomavirus (HPV) is associated with a subset of head and neck squamous cell carcinoma (HNSCC). Between 15% and 35% of HNSCCs harbor HPV DNA. Demographic and exposure differences between HPV-positive (HPV⁺) and negative (HPV^–) HNSCCs suggest that HPV⁺ tumors may constitute a subclass with different biology, whereas clinical differences have also been observed. Gene expression profiles of HPV⁺ and HPV^– tumors were compared with further exploration of the biological effect of HPV in HNSCC. Thirty-six HNSCC tumors were analyzed using Affymetrix Human 133U Plus 2.0 GeneChip and for HPV by PCR and real-time PCR. Eight of 36 (22%) tumors were positive for HPV subtype 16. Statistical analysis using Significance Analysis of Microarrays based on HPV status as a supervising variable resulted in a list of 91 genes that were differentially expressed with statistical significance. Results for a subset of these genes were verified by real-time PCR. Genes highly expressed in HPV⁺ samples included cell cycle regulators (p16^INK4A, p18, and CDC7) and transcription factors (TAF7L, RFC4, RPA2, and TFDP2). The microarray data were also investigated by mapping genes by chromosomal location (DIGMAP). A large number of genes on chromosome 3q24-qter had high levels of expression in HPV⁺ tumors. Further investigation of differentially expressed genes may reveal the unique pathways in HPV⁺ tumors that may explain the different natural history and biological properties of these tumors. These properties may be exploited as a target of novel therapeutic agents in HNSCC treatment.

This article has been cited by other articles:

				M. L. Gillison, G. D'Souza, W. Westra, E. Sugar, W. Xiao, S. Begum, and R. Viscidi Distinct Risk Factor Profiles for Human Papillomavirus Type 16-Positive and Human Papillomavirus Type 16-Negative Head and Neck Cancers J Natl Cancer Inst, March 19, 2008; 100(6): 407 - 420. [Abstract] [Full Text] [PDF]

				D. Pyeon, M. A. Newton, P. F. Lambert, J. A. den Boon, S. Sengupta, C. J. Marsit, C. D. Woodworth, J. P. Connor, T. H. Haugen, E. M. Smith, et al. Fundamental Differences in Cell Cycle Deregulation in Human Papillomavirus-Positive and Human Papillomavirus-Negative Head/Neck and Cervical Cancers Cancer Res., May 15, 2007; 67(10): 4605 - 4619. [Abstract] [Full Text] [PDF]

				F. Perrone, S. Suardi, E. Pastore, P. Casieri, M. Orsenigo, S. Caramuta, G. Dagrada, M. Losa, L. Licitra, P. Bossi, et al. Molecular and Cytogenetic Subgroups of Oropharyngeal Squamous Cell Carcinoma. Clin. Cancer Res., November 15, 2006; 12(22): 6643 - 6651. [Abstract] [Full Text] [PDF]

				C. H. Chung, K. Ely, L. McGavran, M. Varella-Garcia, J. Parker, N. Parker, C. Jarrett, J. Carter, B. A. Murphy, J. Netterville, et al. Increased Epidermal Growth Factor Receptor Gene Copy Number Is Associated With Poor Prognosis in Head and Neck Squamous Cell Carcinomas J. Clin. Oncol., September 1, 2006; 24(25): 4170 - 4176. [Abstract] [Full Text] [PDF]

				C. H. Chung, J. S. Parker, K. Ely, J. Carter, Y. Yi, B. A. Murphy, K. K. Ang, A. K. El-Naggar, A. M. Zanation, A. J. Cmelak, et al. Gene Expression Profiles Identify Epithelial-to-Mesenchymal Transition and Activation of Nuclear Factor-{kappa}B Signaling as Characteristics of a High-risk Head and Neck Squamous Cell Carcinoma Cancer Res., August 15, 2006; 66(16): 8210 - 8218. [Abstract] [Full Text] [PDF]