Genetic Patterns in Head and Neck Cancers That Contain or Lack Transcriptionally Active Human Papillomavirus

• Published in: JNCI : Journal of the National Cancer Institute 2004-07, Vol.96 (13), p.998-1006
• Main Authors: Braakhuis, Boudewijn J. M., Snijders, Peter J. F., Keune, Willem-Jan H., Meijer, Chris J. L. M., Ruijter-Schippers, Henrique J., Leemans, C. René, Brakenhoff, Ruud H.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Biological and medical sciences; Cancer; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - virology; Case-Control Studies; Chromosomes; Deoxyribonucleic acid; DNA; DNA, Viral - genetics; Female; Gene Expression Regulation, Neoplastic; Genes; Genes, p53; Head and Neck Neoplasms - genetics; Head and Neck Neoplasms - virology; Human papillomavirus; Human papillomavirus 16; Humans; Loss of Heterozygosity; Male; Medical sciences; Microsatellite Repeats; Middle Aged; Mutation; Oncogene Proteins, Viral - genetics; Oncology; Otorhinolaryngology (head neck, general aspects and miscellaneous); Otorhinolaryngology. Stomatology; Papillomaviridae - genetics; Papillomaviridae - isolation & purification; Papillomavirus E7 Proteins; Papillomavirus Infections - complications; Papillomavirus Infections - virology; Repressor Proteins; RNA, Messenger - isolation & purification; Sexually transmitted diseases; STD; Transcription, Genetic; Tumors
• ISSN: 0027-8874; 1460-2105
• DOI: 10.1093/jnci/djh183

Background: Transcriptionally active high-risk human papilloma viruses (HPVs), particularly HPV type 16 (HPV16), are found in a subset of head and neck squamous-cell carcinomas (HNSCCs). HPV16-associated carcinogenesis is mediated by expression of the viral E6 and E7 oncoproteins, which cause deregulation of the cell cycle by inactivating p53 and pRb, respectively. We tested the hypothesis that HPV-associated HNSCCs display a pattern of genetic alterations different from those of HNSCCs without HPV DNA. Methods: Polymerase chain reaction–based assays were used to examine 143 consecutive HNSCCs (106 of the oral cavity and 37 of the oropharynx) for the presence of HPV DNA and for viral E6 and/or E7 messenger RNA (mRNA) expression. The HPV DNA–and E6 and E7 mRNA–positive HNSCCs and an equal number of HPV DNA–negative HNSCCs were further analyzed for mutations in TP53, the gene encoding p53, and for allelic loss of 28 microsatellite markers at chromosome arms 3p, 6q, 8p, 9p, 13q, 17p, and 18q, including markers located in regions of chromosome arms 9p and 17p that harbor genes involved the p53 and pRb pathways. All statistical tests were two-sided. Results: Twenty-four (16.7%) of the 143 HNSCCs were positive for HPV16 DNA, and 12 of these HNSCCs (8.4% of total number) expressed E6 and E7 mRNAs. None of the HPV DNA–and E6/E7 mRNA–positive tumors had TP53 gene mutations, whereas nine (75%) of the 12 HPV DNA–negative tumors had such mutations (P