title: Clonal history of papillomavirus-induced dysplasia in the female lower genital tract.
abstract: BACKGROUND
  Dysplastic lesions of the vagina or the vulva often occur in women who have a previous history of cervical dysplasia. Most lesions in the female lower genital tract are induced by infections with high-risk oncogenic human papillomaviruses (HR-HPVs), including HPV16 and HPV18. HR-HPV genomes frequently integrate into host cell chromosomes at random sites. We analyzed viral integration sites in multiple metachronous lesions of the lower genital tract from women previously treated for HR-HPV-positive cervical dysplasia or cancer to determine whether the metachronous lesions emerged from a single common preexisting dysplastic cell clone or as consequence of independent HR-HPV infection events in the female lower genital tract.
  
  
  METHODS
  From among 1500 patients with anogenital lesions, seven patients with high-grade vaginal or vulvar lesions and with a previous history of cervical disease (five with prior high-grade cervical dysplasia and two with a history of cervical cancer) were included in this study. Integration sites of HPV16 or HPV18 in vaginal or vulvar lesions were mapped by an adaptor ligation polymerase chain reaction (PCR) method. The sequence information was used to design an integrate-specific PCR assay that was applied to DNA extracted from archival paraffin-embedded material derived from biopsy samples of cervical lesions.
  
  
  RESULTS
  Identical HPV DNA integration loci were found in vaginal or vulvar and cervical samples of all lesions available for four of the five patients with a prior history of high-grade cervical dysplasia and for both patients with a history of cervical cancer.
  
  
  CONCLUSIONS
  These data indicate that high-grade dysplastic lesions in the female lower genital tract may emerge primarily as monoclonal lesions from a transformed cell population derived from the uterine cervix.
authors.affiliation: Department of Molecular Pathology/Applied Tumor Biology, Institute of Pathology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Vinokurova
authors.forename: Nicolas
authors.initials: N
authors.lastname: Wentzensen
authors.forename: Jens
authors.initials: J
authors.lastname: Einenkel
authors.forename: Ruediger
authors.initials: R
authors.lastname: Klaes
authors.forename: Corina
authors.initials: C
authors.lastname: Ziegert
authors.forename: Peter
authors.initials: P
authors.lastname: Melsheimer
authors.forename: Heike
authors.initials: H
authors.lastname: Sartor
authors.forename: Lars-Christian
authors.initials: LC
authors.lastname: Horn
authors.forename: Michael
authors.initials: M
authors.lastname: Höckel
authors.forename: Magnus
authors.initials: M
authors.lastname: von Knebel Doeberitz
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000821:virology; D002471:Cell Transformation, Neoplastic; D002999:Clone Cells; D004279:DNA, Viral / Q000302:isolation & purification; D005260:Female; D052162:Human papillomavirus 16 / Q000302:isolation & purification; D052161:Human papillomavirus 18 / Q000302:isolation & purification; D006801:Humans; D008875:Middle Aged; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000150:complications*; D016133:Polymerase Chain Reaction; D012107:Research Design; D002578:Uterine Cervical Dysplasia / Q000473:pathology / Q000821:virology*; D002583:Uterine Cervical Neoplasms / Q000473:pathology / Q000821:virology*; D014623:Vaginal Diseases / Q000821:virology
chemical_list: D004279:DNA, Viral