title: Gene expression differences associated with human papillomavirus status in head and neck squamous cell carcinoma.
abstract: 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.
authors.affiliation: Department of Cancer Biology, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-6307, USA.
authors.forename: Robbert J C
authors.initials: RJ
authors.lastname: Slebos
authors.forename: Yajun
authors.initials: Y
authors.lastname: Yi
authors.forename: Kim
authors.initials: K
authors.lastname: Ely
authors.forename: Jesse
authors.initials: J
authors.lastname: Carter
authors.forename: Amy
authors.initials: A
authors.lastname: Evjen
authors.forename: Xueqiong
authors.initials: X
authors.lastname: Zhang
authors.forename: Yu
authors.initials: Y
authors.lastname: Shyr
authors.forename: Barbara M
authors.initials: BM
authors.lastname: Murphy
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Cmelak
authors.forename: Brian B
authors.initials: BB
authors.lastname: Burkey
authors.forename: James L
authors.initials: JL
authors.lastname: Netterville
authors.forename: Shawn
authors.initials: S
authors.lastname: Levy
authors.forename: Wendell G
authors.initials: WG
authors.lastname: Yarbrough
authors.forename: Christine H
authors.initials: CH
authors.lastname: Chung
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000821:virology*; D002874:Chromosome Mapping; D002877:Chromosomes, Human / Q000235:genetics; D016000:Cluster Analysis; D003663:Decision Trees; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D027383:Papillomaviridae / Q000235:genetics*; D012367:RNA, Viral / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D012367:RNA, Viral