title: Chromosome stability in tonsillar squamous cell carcinoma is associated with HPV16 integration and indicates a favorable prognosis.
abstract: Tonsillar squamous cell carcinoma (TSCC) is frequently associated with human papillomavirus (HPV) and chromosome instability. Data from cellular model systems are, however, controversial concerning a relation between HPV and chromosome instability development. Here we studied this association in 77 primary TSCC with known clinical outcome and cell cycle protein expression profiles. Thirty-two tumors (42%) showed HPV16-integration. All 77 cases were analyzed by fluorescence in situ hybridization using chromosome 1- and 7-specific centromere DNA probes to detect chromosome instability, indicated by the presence of chromosome imbalances and/or polyploidization for these chromosomes. In addition, eight HPV-positive dysplasias, seven of which were adjacent to a carcinoma, were analyzed. Disomy for chromosome 1 and 7 was present in 29 out of 77 TSCC (38%), of which 19 were HPV16-positive (p = 0.002). Aneusomy was observed in the remaining 48 TSCC, of which 13 were HPV-positive. Aneusomies correlated significantly with tobacco- and alcohol consumption (p = 0.001 and p = 0.016, respectively) and a higher T-stage (p = 0.018). Both HPV-positivity and chromosome disomy were significantly associated with a favorable disease-free survival (p = 0.001 and p = 0.025, respectively). Particularly in the HPV16-positive group chromosome instability is a very strong indicator for an unfavorable prognosis (p = 0.032). In the dysplasias an identical HPV and chromosome copy number status was identified as in the adjacent tumors. We conclude that HPV-positive TSCC and their precursor lesions are more often genetically stable than HPV-negative lesions and that these tumors are associated with a favorable prognosis. Chromosome instability is an indicator for unfavorable prognosis, particularly in the HPV-positive patient group.
authors.affiliation: Department of Otorhinolaryngology and Head and Neck Surgery, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, The Netherlands. Jeroenmooren@hotmail.com
authors.forename: Jeroen J
authors.initials: JJ
authors.lastname: Mooren
authors.forename: Bernd
authors.initials: B
authors.lastname: Kremer
authors.forename: Sandra M H
authors.initials: SM
authors.lastname: Claessen
authors.forename: Adri C
authors.initials: AC
authors.lastname: Voogd
authors.forename: Fredrik J
authors.initials: FJ
authors.lastname: Bot
authors.forename: J
authors.initials: J
authors.lastname: Peter Klussmann
authors.forename: Christian U
authors.initials: CU
authors.lastname: Huebbers
authors.forename: Anton H N
authors.initials: AH
authors.lastname: Hopman
authors.forename: Frans C S
authors.initials: FC
authors.lastname: Ramaekers
authors.forename: Ernst-Jan M
authors.initials: EJ
authors.lastname: Speel
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology / Q000821:virology; D043171:Chromosomal Instability; D015342:DNA Probes; D052162:Human papillomavirus 16 / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D011379:Prognosis; D014067:Tonsillar Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology; D016662:Virus Integration
chemical_list: D015342:DNA Probes