title: HPV E6/E7 mRNA versus HPV DNA biomarker in cervical cancer screening of a group of Macedonian women.
abstract: High risk types of human papillomaviruses E6/E7 oncogenes and their association with tumor suppressor genes products are the key factors of cervical carcinogenesis. This study proposed them as specific markers for cervical dysplasia screening. The aim of the study is to compare the clinical and prognostic significance of HPV E6/E7 mRNA as an early biomarker versus HPV DNA detection and cytology in triage of woman for cervical cancer. The study group consists of 413 women: 258 NILM, 26 ASC-US, 81 LSIL, 41 HSIL, and 7 unsatisfactory cytology. HPV4AACE screening, real-time multiplex PCR and MY09/11 consensus PCR primers methods were used for the HPV DNA detection. The real-time multiplex nucleic acid sequence-based assay (NucliSENS EasyQ HPV assay) was used for HPV E6/E7 mRNA detection of the five most common high risk HPV types in cervical cancer (16, 18, 31, 33, and 45). The results show that HPV E6/E7 mRNA testing had a higher specificity 50% (95% CI 32-67) and positive predictive value (PPV) 62% (95% CI 46-76) for CIN2+ compared to HPV DNA testing that had specificity of 18% (95% CI 7-37) and PPV 52% (95% CI 39-76) respectively. The higher specificity and PPV of HPV E6/E7 mRNA testing are valuable in predicting insignificant HPV DNA infection among cases with borderline cytological finding. It can help in avoiding aggressive procedures (biopsies and over-referral of transient HPV infections) as well as lowering patient's anxiety and follow up period.
authors.affiliation: Institute of Public Health of R. Macedonia, Skopje, Republic of Macedonia.
authors.forename: Sotirija
authors.initials: S
authors.lastname: Duvlis
authors.affiliation: Research Center for Genetic Engineering and Biotechnology "Georgi D. Efremov", Macedonian Academy of Science and Arts, Skopje, Republic of Macedonia.
authors.forename: Katerina
authors.initials: K
authors.lastname: Popovska-Jankovic
authors.affiliation: Institute of Public Health of R. Macedonia, Skopje, Republic of Macedonia.
authors.forename: Zorica Sarafinovska
authors.initials: ZS
authors.lastname: Arsova
authors.affiliation: Institute of Public Health of R. Macedonia, Skopje, Republic of Macedonia.
authors.forename: Shaban
authors.initials: S
authors.lastname: Memeti
authors.affiliation: Faculty of Computer Science and Engineering, Ss. Cyril and Methodius University of Skopje, Skopje, Republic of Macedonia.
authors.forename: Zaneta
authors.initials: Z
authors.lastname: Popeska
authors.affiliation: Research Center for Genetic Engineering and Biotechnology "Georgi D. Efremov", Macedonian Academy of Science and Arts, Skopje, Republic of Macedonia.
authors.forename: Dijana
authors.initials: D
authors.lastname: Plaseska-Karanfilska
mesh_terms: D000328:Adult; D000368:Aged; D052685:Alphapapillomavirus / Q000235:genetics; D065309:Atypical Squamous Cells of the Cervix / Q000821:virology; D015415:Biomarkers; D004279:DNA, Viral / Q000032:analysis; D055088:Early Detection of Cancer / Q000379:methods*; D005260:Female; D006115:Greece; D061809:Human Papillomavirus DNA Tests; D006801:Humans; D008875:Middle Aged; D060885:Multiplex Polymerase Chain Reaction; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D027383:Papillomaviridae / Q000235:genetics*; D030361:Papillomavirus Infections / Q000821:virology; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D012367:RNA, Viral / Q000032:analysis* / Q000235:genetics; D012680:Sensitivity and Specificity; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000517:prevention & control* / Q000821:virology; D055815:Young Adult
chemical_list: D015415:Biomarkers; D004279:DNA, Viral; D009856:Oncogene Proteins, Viral; D012333:RNA, Messenger; D012367:RNA, Viral
keywords: HPV DNA; HPV E6/E7 mRNA; PPV; cervical cancer screening; specificity