title: Determinants of Viral Oncogene E6-E7 mRNA Overexpression in a Population-Based Large Sample of Women Infected by High-Risk Human Papillomavirus Types.
abstract: Cervical cancer screening by human papillomavirus (HPV) DNA testing with cytology triage is more effective than cytology testing. Compared to cytology, the HPV DNA test's higher sensitivity, which allows better protection with longer intervals, makes it necessary to triage the women with a positive result to compensate its lower specificity. We are conducting a large randomized clinical trial (New Technologies for Cervical Cancer 2 [NTCC2]) within organized population-based screening programs in Italy using HPV DNA as the primary screening test to evaluate, by the Aptima HPV assay (Hologic), the use of HPV E6-E7 mRNA in a triage test in comparison to cytology. By the end of June 2016, data were available for 35,877 of 38,535 enrolled women, 2,651 (7.4%) of whom were HPV DNA positive. Among the samples obtained, 2,453 samples were tested also by Aptima, and 1,649 (67.2%) gave a positive result. The proportion of mRNA positivity was slightly higher among samples tested for HPV DNA by the Cobas 4800 HPV assay (Roche) than by the Hybrid Capture 2 (HC2) assay (Qiagen). In our setting, the observed E6-E7 mRNA positivity rate, if used as a triage test, would bring a rate of immediate referral to colposcopy of about 4 to 5%. This value is higher than that observed with cytology triage for both immediate and delayed referrals to colposcopy. By showing only a very high sensitivity and thus allowing a longer interval for HPV DNA-positive/HPV mRNA-negative women, a triage by this test might be more efficient than by cytology.
authors.affiliation: Interinstitutional Epidemiology Unit, AUSL, Reggio Emilia, Italy paolo.giorgirossi@ausl.re.it.|Arcispedale S. Maria Nuova, IRCCS, Reggio Emilia, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Giorgi Rossi
authors.affiliation: Cancer Research and Prevention Institute (ISPO), Cancer Prevention Laboratory, HPV Laboratory and Molecular Oncology Unit, Florence, Italy.
authors.forename: Simonetta
authors.initials: S
authors.lastname: Bisanzi
authors.affiliation: Centro Unico Screening Cervico-Vaginale, Turin, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Allia
authors.affiliation: Cancer Research and Prevention Institute (ISPO), Cancer Prevention Laboratory, HPV Laboratory and Molecular Oncology Unit, Florence, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mongia
authors.affiliation: Cancer Research and Prevention Institute (ISPO), Cancer Prevention Laboratory, HPV Laboratory and Molecular Oncology Unit, Florence, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Carozzi
authors.affiliation: Centro Unico Screening Cervico-Vaginale, Turin, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Gillio-Tos
authors.affiliation: Centro Unico Screening Cervico-Vaginale, Turin, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: De Marco
authors.affiliation: Center for Cancer Epidemiology and Prevention (CPO), Turin, Italy.
authors.forename: Guglielmo
authors.initials: G
authors.lastname: Ronco
authors.affiliation: Laboratorio Unico di Screening USL Umbria 1, Perugia, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Gustinucci
authors.affiliation: Istituto Oncologico Veneto (IOV), IRCCS, Padua, Italy.
authors.forename: Annarosa
authors.initials: A
authors.lastname: Del Mistro
authors.affiliation: Istituto Oncologico Veneto (IOV), IRCCS, Padua, Italy.
authors.forename: Helena
authors.initials: H
authors.lastname: Frayle
authors.affiliation: Cancer Research and Prevention Institute (ISPO), Cancer Prevention Laboratory, HPV Laboratory and Molecular Oncology Unit, Florence, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Iossa
authors.affiliation: Cancer Research and Prevention Institute (ISPO), Cancer Prevention Laboratory, HPV Laboratory and Molecular Oncology Unit, Florence, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Fantacci
authors.affiliation: Cancer Research and Prevention Institute (ISPO), Cancer Prevention Laboratory, HPV Laboratory and Molecular Oncology Unit, Florence, Italy.
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Pompeo
authors.affiliation: Laboratorio Unico di Screening USL Umbria 1, Perugia, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Cesarini
authors.affiliation: Laboratorio Unico di Screening USL Umbria 1, Perugia, Italy.
authors.forename: Simonetta
authors.initials: S
authors.lastname: Bulletti
authors.affiliation: Laboratorio Unico di Screening USL Umbria 1, Perugia, Italy.
authors.forename: Basilio
authors.initials: B
authors.lastname: Passamonti
authors.affiliation: Istituto Oncologico Veneto (IOV), IRCCS, Padua, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Rizzi
authors.affiliation: ULSS 17 Este-Monselice, Este, Padua, Italy.
authors.forename: Maria Gabriella
authors.initials: MG
authors.lastname: Penon
authors.affiliation: Assessorato alla Salute, Regione Lazio, Rome, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Barca
authors.affiliation: Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Benevolo
mesh_terms: D000328:Adult; D003430:Cross-Sectional Studies; D055088:Early Detection of Cancer / Q000379:methods*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007558:Italy; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques / Q000379:methods*; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000175:diagnosis* / Q000821:virology; D012333:RNA, Messenger / Q000032:analysis* / Q000235:genetics; D012367:RNA, Viral / Q000032:analysis* / Q000235:genetics; D012680:Sensitivity and Specificity
chemical_list: D009856:Oncogene Proteins, Viral; D012333:RNA, Messenger; D012367:RNA, Viral
keywords: HPV E6-E7 oncogene mRNA; biomarkers; cervical cancer screening; human papillomavirus