title: Expression of E6/E7 mRNA from 'high risk' human papillomavirus in relation to CIN grade, viral load and p16INK4a.
abstract: Detection of E6/E7 mRNA expression with real-time nucleic acid sequence-based amplification assay (NASBA) method (PreTect HPV-Proofer) from high-risk types of human papillomaviruses (HR-HPV) were compared with the presence of viral load, determined with quantitative real-time PCR in 80 cervical samples. Results regarding positivity and typing were in agreement using the two methods. However, there was no correlation between viral loads for HPV 16 or 18/45 and oncogene expression. Among 15 women with low grade atypia detected at a population-based cytology screening, and scored as 'within normal limits' according to histopathology, 14% were positive for oncogene expression, whereas 71% were HR-HPV positive. A correlation was observed between HR-HPV oncogene expression and high scores of p16(INK4a) positivity. Since HPV-Proofer detects full-length E6/E7 mRNA, a positive result should correlate with presence of integrated HPV, loss of HPV replication and stabilized E6/E7 full-length mRNA expression. Such expression from integrated HR-HPV generates a high and stable expression of full-length E6 proteins, which explains why a positive HPV-Proofer result was independent of viral load and correlate with high expression of p16(INK4a). Thus, E6/E7 oncogene expression analysis yielded information, which is consistent with and will complement the results from a real-time PCR method in a clinical prognostic procedure.
authors.affiliation: Department for Clinical Science, Intervention and Technology, Division of Obstetrics and Gynecology, Karolinska University Hospital, Huddinge, Karolinska Institute, S-141 86 Stockholm, Sweden. sonia.anderson@telia.com
authors.forename: Sonia
authors.initials: S
authors.lastname: Andersson
authors.forename: Berit
authors.initials: B
authors.lastname: Hansson
authors.forename: Ingrid
authors.initials: I
authors.lastname: Norman
authors.forename: Vera
authors.initials: V
authors.lastname: Gaberi
authors.forename: Miriam
authors.initials: M
authors.lastname: Mints
authors.forename: Anders
authors.initials: A
authors.lastname: Hjerpe
authors.forename: Frank
authors.initials: F
authors.lastname: Karlsen
authors.forename: Bo
authors.initials: B
authors.lastname: Johansson
mesh_terms: D000328:Adult; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism*; D004279:DNA, Viral / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D006801:Humans; D008875:Middle Aged; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D027383:Papillomaviridae / Q000235:genetics; D050725:Papillomavirus E7 Proteins; D030361:Papillomavirus Infections / Q000235:genetics / Q000378:metabolism / Q000821:virology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism / Q000821:virology*; D019562:Viral Load; D002578:Uterine Cervical Dysplasia / Q000235:genetics / Q000378:metabolism / Q000821:virology*
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012333:RNA, Messenger; D012367:RNA, Viral; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16