title: 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.
abstract: 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.
authors: Department of Anatomic Pathology, Faculty of Medicine, Memorial University, St. John's, Newfoundland and Labrador, Canada.
authors: Reza
authors: R
authors: Alaghehbandan
authors: Daniel
authors: D
authors: Fontaine
authors: James
authors: J
authors: Bentley
authors: Nicholas
authors: N
authors: Escott
authors: Prafull
authors: P
authors: Ghatage
authors: Adrian
authors: A
authors: Lear
authors: Francois
authors: F
authors: Coutlee
authors: Samuel
authors: S
authors: Ratnam
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D061809:Human Papillomavirus DNA Tests / Q000379:methods*; D006801:Humans; D008875:Middle Aged; D009856:Oncogene Proteins, Viral / Q000235:genetics* / Q000378:metabolism; D027383:Papillomaviridae / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012372:ROC Curve; D012680:Sensitivity and Specificity; D014218:Triage; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis / Q000473:pathology* / Q000821:virology; D055815:Young Adult
chemical_list: D009856:Oncogene Proteins, Viral; D012333:RNA, Messenger
keywords: ASCUS triage; CIN 2+; HC2; LSIL triage; PreTect HPV-proofer; ProEx C