title: The diagnostic accuracy of E6 & 7 mRNA detection as a primary screening test for the detection of severe cervical lesions.
abstract: OBJECTIVE
  This prospective accuracy study aimed to assess the diagnostic accuracy of nucleic acid sequence amplification (NASBA) and flow cytometry for E6/7 human papillomavirus (HPV) mRNA detection as a primary screening test compared to cytology in the triage of severe cervical intraepithelial neoplasia (CIN) lesions.
  
  
  METHODS
  1083 women referred to our outpatient gynecology clinics for a routine Pap test were recruited. Residual material of the Pap smears was tested by NASBA and by flow cytometry for E6/7 mRNA expression. Biopsy results were used as reference standards. The accuracy indices of both techniques and of NASBA type-16 HPV were assessed for the detection of CIN2+ lesions and were compared to cytology.
  
  
  RESULTS
  An increased lesion severity was associated with increased positivity rates of both NASBA and flow cytometry tests (x(2), p<0.001). A positive correlation between NASBA and flow cytometry was identified when these methods were examined with the Phi coefficient (value 0.369, 95% confidence interval [95%CI] : 0.307-0.426). Furthermore, NASBA (89.7 vs 57.7%, p<0.0005) and flow cytometry (77.3 vs 57.7%, p<0.0005) exhibited higher specificity rates than cytology. However, their sensitivity rates did not exceed those of cytology (NASBA:69.8 vs 84.6%, p=0.051; flow cytometry: 69.12 vs 84.6%, p=0.043).
  
  
  CONCLUSIONS
  Both NASBA and flow cytometry exhibited increased specificity for the triage of CIN2+ lesions. However, their relatively lower sensitivity and higher positivity rates when compared to cytology do not make them ideal for a primary screening test. Hence, the role of mRNA detection in the screening for severe cervical lesions remains to be clarified.
authors: 3rd Department of Obstetrics and Gynecology, University of Athens Medical School, "Attikon" University Hospital, Chaidari, Athens, Greece.
authors: Vasiliki
authors: V
authors: Stathopoulou
authors: George
authors: G
authors: Koliopoulos
authors: Dimitrios
authors: D
authors: Zygouris
authors: Asimakis
authors: A
authors: Pappas
authors: Aris
authors: A
authors: Spathis
authors: Petros
authors: P
authors: Karakitsos
authors: Dimitrios
authors: D
authors: Kassanos
authors: Charalambos
authors: C
authors: Chrelias
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D055088:Early Detection of Cancer / Q000379:methods*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008875:Middle Aged; D021141:Nucleic Acid Amplification Techniques; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D050725:Papillomavirus E7 Proteins / Q000235:genetics*; D011446:Prospective Studies; D012333:RNA, Messenger / Q000032:analysis*; D012097:Repressor Proteins / Q000235:genetics*; D012680:Sensitivity and Specificity; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000821:virology; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis* / Q000821:virology
chemical_list: C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16