title: Genomic profiling identifies common HPV-associated chromosomal alterations in squamous cell carcinomas of cervix and head and neck.
abstract: BACKGROUND
  It is well known that a persistent infection with high-risk human papillomavirus (hrHPV) is causally involved in the development of squamous cell carcinomas of the uterine cervix (CxSCCs) and a subset of SCCs of the head and neck (HNSCCs). The latter differ from hrHPV-negative HNSCCs at the clinical and molecular level.
  
  
  METHODS
  To determine whether hrHPV-associated SCCs arising from different organs have specific chromosomal alterations in common, we compared genome-wide chromosomal profiles of 10 CxSCCs (all hrHPV-positive) with 12 hrHPV-positive HNSCCs and 30 hrHPV-negative HNSCCs. Potential organ-specific alterations and alterations shared by SCCs in general were investigated as well.
  
  
  RESULTS
  Unsupervised hierarchical clustering resulted in one mainly hrHPV-positive and one mainly hrHPV-negative cluster. Interestingly, loss at 13q and gain at 20q were frequent in HPV-positive carcinomas of both origins, but uncommon in hrHPV-negative HNSCCs, indicating that these alterations are associated with hrHPV-mediated carcinogenesis. Within the group of hrHPV-positive carcinomas, HNSCCs more frequently showed gains of multiple regions at 8q whereas CxSCCs more often showed loss at 17p. Finally, gains at 3q24-29 and losses at 11q22.3-25 were frequent (>50%) in all sample groups.
  
  
  CONCLUSIONS
  In this study hrHPV-specific, organ-specific, and pan-SCC chromosomal alterations were identified. The existence of hrHPV-specific alterations in SCCs of different anatomical origin, suggests that these alterations are crucial for hrHPV-mediated carcinogenesis.
authors.affiliation: Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands. s.wilting@vumc.nl
authors.forename: Saskia M
authors.initials: SM
authors.lastname: Wilting
authors.forename: Serge J
authors.initials: SJ
authors.lastname: Smeets
authors.forename: Peter J F
authors.initials: PJ
authors.lastname: Snijders
authors.forename: Wessel N
authors.initials: WN
authors.lastname: van Wieringen
authors.forename: Mark A
authors.initials: MA
authors.lastname: van de Wiel
authors.forename: Gerrit A
authors.initials: GA
authors.lastname: Meijer
authors.forename: Bauke
authors.initials: B
authors.lastname: Ylstra
authors.forename: C René
authors.initials: CR
authors.lastname: Leemans
authors.forename: Chris J L M
authors.initials: CJ
authors.lastname: Meijer
authors.forename: Ruud H
authors.initials: RH
authors.lastname: Brakenhoff
authors.forename: Boudewijn J M
authors.initials: BJ
authors.lastname: Braakhuis
authors.forename: Renske D M
authors.initials: RD
authors.lastname: Steenbergen