title: 11q13 amplification status and human papillomavirus in relation to p16 expression defines two distinct etiologies of head and neck tumours.
abstract: Two distinct etiologies of head and neck squamous cell carcinoma (HNSCC) have been proposed, DNA damage owing to tobacco and alcohol exposure and human papillomavirus (HPV) oncogene-mediated transformation. Common genetic alterations in HNSCC include TP53 mutations, 11q13 amplification (amp) and CDKN2A/p16 mutations or promoter methlyation. However, in HPV+ HNSCC it is frequent to observe wild-type TP53 and expression of p16. The relationship of this unusual pattern with 11q13 amp has not been tested. In a retrospective study on 125 HNSCC patients, only 17% (five out of 30) of HPV+ vs 44% (39 out of 89) of HPV - tumours expressed 11q13 amp (adjusted odds ratio (OR)=0.2, 95% confidence interval (CI)=0.1-0.6). A subpopulation of tumours (n=69) were classified according to the three molecular markers, TP53, p16 and 11q13 amp. In addition to wild-type TP53, and p16 expression, HPV+ tumours were more likely not to be amplified at 11q13 (OR=6.5, 95% CI=1.8-23.9). As HPV+ HNSCC lack the genetic alterations which are common in other tumours, we hypothesise that HPV infection may represent an early event in the HNSCC carcinogenic process, thus suggesting a distinct molecular pathway.
authors.affiliation: Department of Human Genetics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA 15261, USA.
authors.forename: C C R
authors.initials: CC
authors.lastname: Ragin
authors.forename: E
authors.initials: E
authors.lastname: Taioli
authors.forename: J L
authors.initials: JL
authors.lastname: Weissfeld
authors.forename: J S
authors.initials: JS
authors.lastname: White
authors.forename: K M
authors.initials: KM
authors.lastname: Rossie
authors.forename: F
authors.initials: F
authors.lastname: Modugno
authors.forename: S M
authors.initials: SM
authors.lastname: Gollin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000821:virology; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics; D005260:Female; D005784:Gene Amplification; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000235:genetics / Q000821:virology*; D012189:Retrospective Studies; D017422:Sequence Analysis, DNA; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral; D016159:Tumor Suppressor Protein p53