TY - JOUR
T1 - 11q13 amplification status and human papillomavirus in relation to p16 expression defines two distinct etiologies of head and neck tumours
AU - Ragin, C. C.R.
AU - Taioli, E.
AU - Weissfeld, J. L.
AU - White, J. S.
AU - Rossie, K. M.
AU - Modugno, F.
AU - Gollin, S. M.
PY - 2006/11/20
Y1 - 2006/11/20
N2 - 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.
AB - 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.
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Carcinoma, Squamous Cell/genetics
KW - Chromosomes, Human, Pair 11/genetics
KW - Cyclin-Dependent Kinase Inhibitor p16/genetics
KW - DNA, Viral/chemistry
KW - Female
KW - Gene Amplification
KW - Head and Neck Neoplasms/genetics
KW - Humans
KW - Male
KW - Middle Aged
KW - Papillomaviridae/genetics
KW - Papillomavirus Infections/genetics
KW - Retrospective Studies
KW - Sequence Analysis, DNA
KW - Survival Rate
KW - Tumor Cells, Cultured
KW - Tumor Suppressor Protein p53/genetics
UR - http://www.scopus.com/inward/record.url?scp=33751038688&partnerID=8YFLogxK
UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=purepublist2023&SrcAuth=WosAPI&KeyUT=WOS:000242046700021&DestLinkType=FullRecord&DestApp=WOS
U2 - 10.1038/sj.bjc.6603394
DO - 10.1038/sj.bjc.6603394
M3 - Article
C2 - 17003776
SN - 0007-0920
VL - 95
SP - 1432
EP - 1438
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 10
ER -