title: Sensitivity, specificity, and clinical value of human papillomavirus (HPV) E6/E7 mRNA assay as a triage test for cervical cytology and HPV DNA test.
abstract: There is evidence that testing for human papillomavirus (HPV) E6/E7 mRNA is more specific than testing for HPV DNA. A retrospective study was carried out to evaluate the performance of the PreTect HPV-Proofer E6/E7 mRNA assay (Norchip) as a triage test for cytology and HPV DNA testing. This study analyzed 1,201 women, 688 of whom had a colposcopy follow-up and 195 of whom had histology-confirmed high-grade intraepithelial neoplasia or worse (CIN2+). The proportion of positive results and the sensitivity and specificity for CIN2+ were determined for HPV mRNA in comparison to HPV DNA and cytology. All data were adjusted for follow-up completeness. Stratified by cytological grades, the HPV mRNA sensitivity was 83% (95% confidence interval [CI] = 63 to 94%) in ASC-US (atypical squamous cells of undetermined significance), 62% (95% CI = 47 to 75%) in L-SIL (low-grade squamous intraepithelial lesion), and 67% (95% CI = 57 to 76%) in H-SIL (high-grade squamous intraepithelial lesion). The corresponding figures were 99, 91, and 96%, respectively, for HPV DNA. The specificities were 82, 76, and 45%, respectively, for HPV mRNA and 29, 13, and 4%, respectively, for HPV DNA. Used as a triage test for ASC-US and L-SIL, mRNA reduced colposcopies by 79% (95% CI = 74 to 83%) and 69% (95% CI = 65 to 74%), respectively, while HPV DNA reduced colposcopies by 38% (95% CI = 32 to 44%) and by 15% (95% CI = 12 to 19%), respectively. As a HPV DNA positivity triage test, mRNA reduced colposcopies by 63% (95% CI = 60 to 66%), having 68% sensitivity (95% CI = 61 to 75%), whereas cytology at the ASC-US+ threshold reduced colposcopies by 23% (95% CI = 20 to 26%), showing 92% sensitivity (95% CI = 87 to 95%). In conclusion, PreTect HPV-Proofer mRNA can serve as a better triage test than HPV DNA to reduce colposcopy referral in both ASC-US and L-SIL. It is also more efficient than cytology for the triage of HPV DNA-positive women. Nevertheless, its low sensitivity demands a strict follow-up of HPV DNA positive-mRNA negative cases.
authors.affiliation: Agency for Public Health Lazio Sanità, Via di Santa Costanza 53, 00198 Rome, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Benevolo
authors.forename: Amina
authors.initials: A
authors.lastname: Vocaturo
authors.forename: Donatella
authors.initials: D
authors.lastname: Caraceni
authors.forename: Deborah
authors.initials: D
authors.lastname: French
authors.forename: Sandra
authors.initials: S
authors.lastname: Rosini
authors.forename: Roberta
authors.initials: R
authors.lastname: Zappacosta
authors.forename: Irene
authors.initials: I
authors.lastname: Terrenato
authors.forename: Lucia
authors.initials: L
authors.lastname: Ciccocioppo
authors.forename: Antonio
authors.initials: A
authors.lastname: Frega
authors.forename: Paolo
authors.initials: P
authors.lastname: Giorgi Rossi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003584:Cytological Techniques / Q000379:methods; D004279:DNA, Viral / Q000235:genetics / Q000302:isolation & purification*; D055088:Early Detection of Cancer / Q000379:methods*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000175:diagnosis* / Q000821:virology; D012333:RNA, Messenger / Q000235:genetics / Q000302:isolation & purification*; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D014481:United States; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis*; D055815:Young Adult
chemical_list: D004279:DNA, Viral; D009856:Oncogene Proteins, Viral; D012333:RNA, Messenger