title: Clinical performance of human papillomavirus E6 and E7 mRNA testing for high-grade lesions of the cervix.
abstract: Infection with high-risk (HR) human papillomavirus (HPV) is the major cause of cervical cancer. However, relatively few infections progress to malignant disease. Progression to malignancy requires the overexpression of the E6 and E7 genes in the integrated HPV genome. It follows that the E6 and E7 transcripts could be useful markers of disease progression. The study presented here tests this possibility, using data from colposcopy and from cytological and histological tests to compare RNA assays for the E6 and E7 genes with DNA testing. A total of 180 women underwent colposcopy, cytology, and biopsy of suspected lesions (143 cases). Cervical brush specimens were analyzed for HPV DNA and for E6 and E7 mRNA. DNA from HR HPV was found in 57.8% of the specimens; E6 and E7 transcripts were found in 45%. The rates of detection of HPV DNA and of E6 and E7 transcripts were 33.3% and 25%, respectively, for specimens with normal findings; 51.4% and 31.9%, respectively, for specimens with cervical intraepithelial neoplasia grade 1 (CIN1); and 61.1% and 44.2% for specimens with CIN2, respectively. All specimens with CIN3 and 95.5% of specimens from patients with squamous cell carcinoma were positive by both assays. Thirty-seven patients with normal colposcopy findings did not undergo biopsy. HPV DNA and mRNA transcripts were found in 32.4% and 18.9% of these cases, respectively. Comparisons with cytological tests produced similar results. Overall, the mRNA tests showed a higher specificity than the DNA tests for high-grade lesions (72.7% and 56.2%, respectively) and a higher positive predictive value (59.3% and 49.0%, respectively). These findings suggest that mRNA assays could be more powerful than DNA testing for predicting the risk of progression and offer a strong potential as a tool for triage and patient follow-up.
authors.affiliation: Institute of Microbiology, Università Cattolica del Sacro Cuore, Largo A Gemelli 8, Rome 00168, Italy. pcattani@rm.unicatt.it
authors.forename: Paola
authors.initials: P
authors.lastname: Cattani
authors.forename: Gian Franco
authors.initials: GF
authors.lastname: Zannoni
authors.forename: Caterina
authors.initials: C
authors.lastname: Ricci
authors.forename: Sara
authors.initials: S
authors.lastname: D'Onghia
authors.forename: Ilaria Nausica
authors.initials: IN
authors.lastname: Trivellizzi
authors.forename: Aldo
authors.initials: A
authors.lastname: Di Franco
authors.forename: Valerio G
authors.initials: VG
authors.lastname: Vellone
authors.forename: Maria
authors.initials: M
authors.lastname: Durante
authors.forename: Giovanni
authors.initials: G
authors.lastname: Fadda
authors.forename: Giovanni
authors.initials: G
authors.lastname: Scambia
authors.forename: Giovanni
authors.initials: G
authors.lastname: Capelli
authors.forename: Rosa
authors.initials: R
authors.lastname: De Vincenzo
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000821:virology; D002584:Cervix Uteri; D004279:DNA, Viral / Q000032:analysis / Q000235:genetics; D005260:Female; D006801:Humans; D008875:Middle Aged; D009856:Oncogene Proteins, Viral / Q000235:genetics* / Q000378:metabolism; D050725:Papillomavirus E7 Proteins / Q000235:genetics* / Q000378:metabolism; D030361:Papillomavirus Infections / Q000175:diagnosis / Q000821:virology; D016133:Polymerase Chain Reaction / Q000379:methods; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D012367:RNA, Viral / Q000032:analysis / Q000235:genetics; D012680:Sensitivity and Specificity; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis / Q000821:virology; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis / Q000821:virology
chemical_list: D004279:DNA, Viral; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012333:RNA, Messenger; D012367:RNA, Viral