title: High-risk human papillomavirus seems not involved in DES-related and of limited importance in nonDES related clear-cell carcinoma of the cervix.
abstract: OBJECTIVE
  Over 90% of all cervical adenocarcinoma are caused by a transforming infection with a high-risk type human papillomavirus (hrHPV). Previous studies demonstrated that the association between hrHPV positivity and cervical clear-cell adenocarcinoma (CCAC) varies between 0% and 100%. As approximately 60% of all CCAC are associated with intra-uterine diethylstilbestrol (DES) exposure, we determined in a cohort of both DES-exposed and DES-unexposed women the prevalence of hrHPV infections, and the potential etiological role of hrHPV by additional analysis of p16INK4a and p53 expression.
  
  
  METHODS
  Representative slides of 28 women diagnosed with CCAC were tested for hrHPV by two PCR methods (the clinically validated GP5+/6+ PCR and the very sensitive SPF(10)PCR/LiPA(25)). Fifteen women were DES-exposed, 10 unexposed and of 3 women DES-exposure was unknown. Twenty-one cases with sufficient material were immuno-histochemically stained for p16INK4a and p53.
  
  
  RESULTS
  Seven tumors, of which four DES-exposed and two unexposed tested positive for hrHPV with GP5+/6+ PCR. Thirteen tumors, of which five DES-exposed and seven unexposed, tested positive with SPF(10)PCR/LiPA(25). In one women with unknown exposure, a CCAC tested positive in both assays. Only three cases, none in DES-exposed women, and all positive with both hrHPV assays, revealed diffuse p16INK4a immuno-staining and weak p53 staining as well, supporting indisputable hrHPV involvement.
  
  
  CONCLUSIONS
  Although the prevalence of hrHPV was high, only two DES-unrelated CCAC (25%) and one tumor in a woman with unknown exposure could be attributed to hrHPV.
authors.affiliation: Department of Obstetrics and Gynecology, Erasmus MC University Medical Centre, Rotterdam, The Netherlands. m.kocken@erasmusmc.nl
authors.forename: Mariëlle
authors.initials: M
authors.lastname: Kocken
authors.forename: Astrid
authors.initials: A
authors.lastname: Baalbergen
authors.forename: Peter J F
authors.initials: PJ
authors.lastname: Snijders
authors.forename: Johan
authors.initials: J
authors.lastname: Bulten
authors.forename: Wim G V
authors.initials: WG
authors.lastname: Quint
authors.forename: Frank
authors.initials: F
authors.lastname: Smedts
authors.forename: Chris J L M
authors.initials: CJ
authors.lastname: Meijer
authors.forename: Theo J M
authors.initials: TJ
authors.lastname: Helmerhorst
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000139:chemically induced / Q000209:etiology* / Q000821:virology; D000293:Adolescent; D000328:Adult; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004054:Diethylstilbestrol / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis; D027383:Papillomaviridae / Q000302:isolation & purification*; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012306:Risk; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D002583:Uterine Cervical Neoplasms / Q000139:chemically induced / Q000209:etiology* / Q000821:virology
chemical_list: C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins; D016159:Tumor Suppressor Protein p53; D004054:Diethylstilbestrol