title: Association between human papilloma virus/Epstein-Barr virus coinfection and oral carcinogenesis.
abstract: BACKGROUND
  The recent epidemic of head and neck squamous cell carcinomas associated with human papilloma virus (HPV) has not addressed its association with lymphoid tissue in the oropharynx or the potential role of Epstein-Barr virus (EBV)/HPV coinfection.
  
  
  METHODS
  The prevalence of HPV and EBV infection/coinfection and CD21 mRNA expression were determined in normal and cancerous tissues from the oropharynx using in situ hybridization (ISH), p16, and quantitative reverse transcriptase PCR (qRT-PCR). The effects of coinfection on tumorigenicity were evaluated using proliferation and invasion assays.
  
  
  RESULTS
  Normal oropharynx, tonsil, non-cancer base of tongue (BOT), and BOT from sleep apnea patients demonstrated EBV positivity ranging from 7% to 36% depending on the site and methods of detection used (qRT-PCR or ISH). Among non-malignant BOT samples, HPV positivity was noted only in 20%. The percent of tonsil and BOT cancers positive for HPV (up to 63% and 80%, respectively) or coinfected with HPV/EBV (up to 25% and 70%, respectively) were both significantly associated with cancer status. Notably, HPV/EBV coinfection was observed only in malignant tissue originating in lymphoid-rich oropharynx sites (tonsil, BOT). CD21 mRNA (the major EBV attachment receptor) was detected in tonsil and BOT epithelium, but not in soft-palate epithelium. Coinfected cell lines showed a significant increase in invasiveness (P < 0.01).
  
  
  CONCLUSIONS
  There is a high prevalence of HPV/EBV infection and coinfection in BOT and tonsil cancers, possibly reflecting their origins in lymphoid-rich tissue. In vitro, cells modeling coinfection have an increased invasive potential.
authors.affiliation: Department of Microbiology and Immunology, LSUHSC, Shreveport, LA, USA; Department of Clinical Teaching and Training, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
authors.forename: Ru
authors.initials: R
authors.lastname: Jiang
authors.forename: Oleksandr
authors.initials: O
authors.lastname: Ekshyyan
authors.forename: Tara
authors.initials: T
authors.lastname: Moore-Medlin
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Rong
authors.forename: Sean
authors.initials: S
authors.lastname: Nathan
authors.forename: Xin
authors.initials: X
authors.lastname: Gu
authors.forename: Fleurette
authors.initials: F
authors.lastname: Abreo
authors.forename: Eben L
authors.initials: EL
authors.lastname: Rosenthal
authors.forename: Mingxia
authors.initials: M
authors.lastname: Shi
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Guidry
authors.forename: Rona S
authors.initials: RS
authors.lastname: Scott
authors.forename: Lindsey M
authors.initials: LM
authors.lastname: Hutt-Fletcher
authors.forename: Cherie-Ann O
authors.initials: CA
authors.lastname: Nathan
mesh_terms: D052685:Alphapapillomavirus / Q000502:physiology*; D063646:Carcinogenesis; D002294:Carcinoma, Squamous Cell / Q000821:virology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D060085:Coinfection / Q000821:virology*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis; D020031:Epstein-Barr Virus Infections / Q000821:virology*; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D009361:Neoplasm Invasiveness; D009959:Oropharyngeal Neoplasms / Q000821:virology*; D009960:Oropharynx / Q000821:virology; D010157:Palatal Neoplasms / Q000821:virology; D010160:Palate, Soft / Q000821:virology; D014066:Palatine Tonsil / Q000821:virology; D030361:Papillomavirus Infections / Q000821:virology*; D017464:Receptors, Complement 3d / Q000032:analysis; D012891:Sleep Apnea Syndromes / Q000821:virology; D014059:Tongue / Q000821:virology; D014062:Tongue Neoplasms / Q000821:virology; D014067:Tonsillar Neoplasms / Q000821:virology
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D017464:Receptors, Complement 3d
keywords: Epstein-Barr virus; coinfection; human papilloma virus; oral carcinogenesis; squamous cell carcinoma; tumorigenesis