title: BD-ProExC as adjunct molecular marker for improved detection of CIN2+ after HPV primary screening.
abstract: METHODS
  We investigated the efficacy of 8 cervical cancer screening strategies relative to cytology with emphasis on immunocytochemical detection of high-risk human papillomavirus (hrHPV)-induced cell transformation (BD-ProExC) as a tool of triage following primary cytology or hrHPV testing. 3,126 women were tested with BD-SurePath liquid-based cytology, hrHPV PCR genotyping and BD-ProExC immunostaining, and colposcopy verification to calculate sensitivity and positive predictive value (PPV) in detecting cervical intraepithelial neoplasia (CIN2(+)).
  
  
  RESULTS
  Compared to cytology screening, double testing with cytology and hrHPV resulted in the same sensitivity with a significant increase in the PPV (relative PPV: 1.83). However, twice as many tests were needed. Cytology with atypical squamous cells of undetermined significance (ASC-US) triage and hrHPV testing showed comparative results to double testing requiring only a small increase in number of tests. Screening for hrHPV subtypes 16/18, and ASC-US triage with hrHPV16/18 resulted in significant reductions in sensitivity (ratio: 0.74 and 0.96, respectively). Primary hrHPV/BD-ProExC screening was significantly more sensitive (ratio: 1.63/1.33), but had a significantly lower PPV (ratio: 0.64/0.88). ASC-US triage by BD-ProExC increased the PPV (ratio: 1.90) but decreased the sensitivity (ratio: 0.96). Primary hrHPV screening followed by BD-ProExC triage, led to significant increases in sensitivity (ratio: 1.30) and PPV (ratio: 2.89), and resulted in 55% fewer referrals for colposcopy.
  
  
  CONCLUSIONS
  From the investigated screening strategies, primary hrHPV DNA-based screening followed by BD-ProExC triage was determined to be the best screening strategy.
  
  
  CONCLUSIONS
  Immunocytological triage could be used to perfect hrHPV primary screening.
authors.affiliation: Department of Molecular Pathology (RIATOL), Sonic Healthcare, Emiel Vloorsstraat 9, B-2020, Antwerp, Belgium. Christophe.Depuydt@riatol.be
authors.forename: Christophe E
authors.initials: CE
authors.lastname: Depuydt
authors.forename: Amin P
authors.initials: AP
authors.lastname: Makar
authors.forename: Maya J
authors.initials: MJ
authors.lastname: Ruymbeke
authors.forename: Ina H
authors.initials: IH
authors.lastname: Benoy
authors.forename: Annie J
authors.initials: AJ
authors.lastname: Vereecken
authors.forename: Johannes J
authors.initials: JJ
authors.lastname: Bogers
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D003127:Colposcopy; D004268:DNA-Binding Proteins / Q000235:genetics*; D055088:Early Detection of Cancer / Q000379:methods; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D027383:Papillomaviridae / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000175:diagnosis*; D011446:Prospective Studies; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000821:virology; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis* / Q000821:virology
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins