Performance of proex c and pretect hpv-proofer e6/e7 mrna tests in comparison with the hybrid capture 2 hpv dna test for triaging ascus and lsil cytology

• Published in: Diagnostic cytopathology Vol. 41; no. 9; pp. 767 - 775
• Main Authors: Alaghehbandan, Reza, Fontaine, Daniel, Bentley, James, Escott, Nicholas, Ghatage, Prafull, Lear, Adrian, Coutlee, Francois, Ratnam, Samuel
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.09.2013; Wiley Subscription Services, Inc
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; ASCUS triage; Cervical Intraepithelial Neoplasia - diagnosis; Cervical Intraepithelial Neoplasia - pathology; Cervical Intraepithelial Neoplasia - virology; CIN 2; Female; HC2; Human Papillomavirus DNA Tests - methods; Humans; LSIL triage; Middle Aged; Oncogene Proteins, Viral - genetics; Oncogene Proteins, Viral - metabolism; Papillomaviridae - genetics; PreTect HPV-proofer; ProEx C; RNA, Messenger - genetics; RNA, Messenger - metabolism; ROC Curve; Sensitivity and Specificity; Triage; Uterine Cervical Dysplasia - diagnosis; Uterine Cervical Dysplasia - pathology; Uterine Cervical Dysplasia - virology; Young Adult; ASCUS triage; CIN 2; LSIL triage; ProEx C; PreTect HPV-proofer; HC2
• ISSN: 8755-1039; 1097-0339
• DOI: 10.1002/dc.22944

The clinical usefulness of the ProEx C (Becton Dickinson) and PreTect HPV‐Proofer E6/E7 mRNA tests (Proofer; Norchip) for the triage of ASCUS and LSIL cytology was determined in comparison with the Hybrid Capture 2 HPV DNA test (HC2; Qiagen). The study population consisted of women with a history of abnormal cytology referred to colposcopy. Histology‐confirmed CIN 2+ served as the disease endpoint. The study was based on 1,360 women (mean age 30.7 years), of whom 380 had CIN 2+. Among 315 with ASCUS (CIN 2+, n = 67), the sensitivities of ProEx C, Proofer, and HC2 to detect CIN 2+ were, 71.6, 71.6, and 95.5%, respectively, with a corresponding specificity of 74.6, 74.2, and 35.1%. Among 363 with LSIL (CIN 2+, n = 108), the sensitivities of ProEx C, Proofer, and HC2 were, 67.6, 74.1, and 96.3%, respectively, with a corresponding specificity of 60, 68.2, and 18.4%. Among 225 HC2‐positive ASCUS (CIN 2+, n = 64), 105 tested positive by ProEx C, reducing colposcopy referral by 53.3% and detecting 71.9% of CIN 2+; Proofer was positive in 112/225, reducing colposcopy referral by 50.2% and detecting 75.0% of CIN 2+. Among 312 HC2‐positive LSIL (CIN 2+, n = 104), 160 tested positive by ProEx C, reducing coloposcopy referral by 48.7% and detecting 66.3% of CIN 2+; Proofer was positive in 159/312, reducing colposcopy referral by 49.0% and detecting 75.0% of CIN 2+. In conclusion, both ProEx C and Proofer have a similar performance profile with a significantly higher specificity but lower sensitivity than HC2 for the detection of CIN 2+. Consequently, although they can reduce colposcopy referral, they will miss a proportion of CIN 2+ cases. This is a major limitation and should be taken into account if these tests are considered for ASCUS or LSIL triage. Diagn. Cytopathol. 2013;41:767–775. © 2013 Wiley Periodicals, Inc.