BD-ProExC as Adjunct Molecular Marker for Improved Detection of CIN2+ after HPV Primary Screening

• Published in: Cancer epidemiology, biomarkers & prevention biomarkers & prevention, 2011-04, Vol.20 (4), p.628-637
• Main Authors: DEPUYDT, Christophe E, MAKAR, Amin P, RUYMBEKE, Maya J, BENOY, Ina H, VEREECKEN, Annie J, BOGERS, Johannes J
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Bioindicators; Biological and medical sciences; biomarkers; Biomarkers, Tumor - analysis; Cancer; Cervical cancer; Cervical Intraepithelial Neoplasia - diagnosis; Cervical Intraepithelial Neoplasia - virology; Cervix; Colposcopy; DNA-Binding Proteins - genetics; Early Detection of Cancer - methods; Female; Female genital diseases; Genotyping; Gynecology. Andrology. Obstetrics; Human papillomavirus; Humans; Immunohistochemistry; Medical sciences; Middle Aged; Neoplasia; Papillomaviridae - isolation & purification; Papillomavirus Infections - diagnosis; Polymerase chain reaction; prevention; Prospective Studies; Risk groups; Sensitivity; Squamous cells; Transformation; Tumors; Uterine Cervical Neoplasms - diagnosis; Uterine Cervical Neoplasms - virology; Young Adult
• ISSN: 1055-9965; 1538-7755
• DOI: 10.1158/1055-9965.EPI-10-0818

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(+)). 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. From the investigated screening strategies, primary hrHPV DNA-based screening followed by BD-ProExC triage was determined to be the best screening strategy. Immunocytological triage could be used to perfect hrHPV primary screening.