title: Integration of high-risk human papillomavirus into cellular cancer-related genes in head and neck cancer cell lines.
abstract: Human papillomavirus (HPV)-positive oropharyngeal cancer is generally associated with excellent response to therapy, but some HPV-positive tumors progress despite aggressive therapy. The purpose of this study was to evaluate viral oncogene expression and viral integration sites in HPV16- and HPV18-positive squamous cell carcinoma lines.
  
  
  
  E6/E7 alternate transcripts were assessed by reverse transcriptase-polymerase chain reaction (RT-PCR). Detection of integrated papillomavirus sequences (DIPS-PCR) and sequencing identified viral insertion sites and affected host genes. Cellular gene expression was assessed across viral integration sites.
  
  
  
  All HPV-positive cell lines expressed alternate HPVE6/E7 splicing indicative of active viral oncogenesis. HPV integration occurred within cancer-related genes TP63, DCC, JAK1, TERT, ATR, ETV6, PGR, PTPRN2, and TMEM237 in 8 head and neck squamous cell carcinoma (HNSCC) lines but UM-SCC-105 and UM-GCC-1 had only intergenic integration.
  
  
  
  HPV integration into cancer-related genes occurred in 7 of 9 HPV-positive cell lines and of these 6 were from tumors that progressed. HPV integration into cancer-related genes may be a secondary carcinogenic driver in HPV-driven tumors. © 2017 Wiley Periodicals, Inc. Head Neck 39: 840-852, 2017.
authors.affiliation: Cancer Biology Program, Program in the Biomedical Sciences, Rackham Graduate School, University of Michigan, Ann Arbor, Michigan.|Department of Otolaryngology/Head and Neck Surgery, University of Michigan, Ann Arbor, Michigan.
authors.forename: Heather M
authors.initials: HM
authors.lastname: Walline
authors.affiliation: Department of Otolaryngology/Head and Neck Surgery, University of Michigan, Ann Arbor, Michigan.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Goudsmit
authors.affiliation: Department of Pathology, University of Michigan, Ann Arbor, Michigan.
authors.forename: Jonathan B
authors.initials: JB
authors.lastname: McHugh
authors.affiliation: Department of Otolaryngology/Head and Neck Surgery, University of Michigan, Ann Arbor, Michigan.|Department of Otolaryngology, University of Cincinnati, Cincinnati, Ohio.
authors.forename: Alice L
authors.initials: AL
authors.lastname: Tang
authors.affiliation: Department of Otolaryngology/Head and Neck Surgery, University of Michigan, Ann Arbor, Michigan.
authors.forename: John H
authors.initials: JH
authors.lastname: Owen
authors.affiliation: National Cancer Centre - Cancer Science Institute of Singapore, Duke-NUS Graduate Medical School, Singapore.
authors.forename: Bin T
authors.initials: BT
authors.lastname: Teh
authors.affiliation: Department of Otolaryngology/Head and Neck Surgery, University of Michigan, Ann Arbor, Michigan.
authors.forename: Erin
authors.initials: E
authors.lastname: McKean
authors.affiliation: Department of Human Genetics, University of Michigan, Ann Arbor, Michigan.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Glover
authors.affiliation: Department of Otolaryngology/Head and Neck Surgery, University of Michigan, Ann Arbor, Michigan.
authors.forename: Martin P
authors.initials: MP
authors.lastname: Graham
authors.affiliation: Department of Otolaryngology/Head and Neck Surgery, University of Michigan, Ann Arbor, Michigan.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Prince
authors.affiliation: Department of Otolaryngology/Head and Neck Surgery, University of Michigan, Ann Arbor, Michigan.
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Chepeha
authors.affiliation: Department of Otolaryngology/Head and Neck Surgery, University of Michigan, Ann Arbor, Michigan.
authors.forename: Steven B
authors.initials: SB
authors.lastname: Chinn
authors.affiliation: Department of Otolaryngology, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Ferris
authors.affiliation: Department of Human Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Susanne M
authors.initials: SM
authors.lastname: Gollin
authors.affiliation: Department of Otolaryngology, Heinrich Heine University, Dusseldorf, Germany.|Department of Otolaryngology, University of Ulm, Ulm, Germany.
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Hoffmann
authors.affiliation: Department of Otolaryngology, Heinrich Heine University, Dusseldorf, Germany.|Department of Otolaryngology, Technical University Medical Center, Munich, Germany.
authors.forename: Henning
authors.initials: H
authors.lastname: Bier
authors.affiliation: Department of Otolaryngology/Head and Neck Surgery, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Ruud
authors.initials: R
authors.lastname: Brakenhoff
authors.affiliation: Department of Otolaryngology/Head and Neck Surgery, University of Michigan, Ann Arbor, Michigan.
authors.forename: Carol R
authors.initials: CR
authors.lastname: Bradford
authors.affiliation: Department of Otolaryngology/Head and Neck Surgery, University of Michigan, Ann Arbor, Michigan.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Carey
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology / Q000821:virology*; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000473:pathology / Q000821:virology*; D052162:Human papillomavirus 16 / Q000502:physiology*; D052161:Human papillomavirus 18 / Q000502:physiology*; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000378:metabolism; D016662:Virus Integration / Q000502:physiology*
chemical_list: D009856:Oncogene Proteins, Viral
keywords: cancer; head and neck squamous cell carcinoma (HNSCC); human papillomavirus (HPV); integration; oropharynx