title: HPV E6/E7 mRNA testing is more specific than cytology in post-colposcopy follow-up of women with negative cervical biopsy.
abstract: BACKGROUND
  In Norway, women with negative or low-grade cervical biopsies (normal/CIN1) are followed up after six months in order to decide on further follow-up or recall for screening at three-year intervals. A high specificity and positive predictive value (PPV) of the triage test is important to avoid unnecessary diagnostic and therapeutic procedures whereas a low risk of high-grade disease among triage negative women assures safety.
  
  
  METHODS
  At the University Hospital of North Norway, cytology and the HPV mRNA test PreTect HPV-Proofer, detecting E6/E7 mRNA from HPV types 16, 18, 31, 33 and 45, are used in post-colposcopy follow-up of women with negative or low-grade biopsy. In this study, women with negative biopsy after high grade cytology (ASC-H/HSIL) and/or positive HPV mRNA test in the period 2005-2009 were included (n = 520). Histologically confirmed cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) was used as study endpoint.
  
  
  RESULTS
  Of 520 women with negative or low-grade biopsy, 124 women (23.8%) had CIN2+ in follow-up biopsy. The sensitivity and specificity of the HPV mRNA test were 89.1% (95% CI, 80.1-98.1) and 92.5% (95% CI, 88.2-96.7), respectively. The ratios of sensitivity, specificity and PPV of HPV mRNA testing compared to repeat cytology for finding CIN2+ was 1.05 (95% CI: 0.92-1.21), 1.21 (95% CI: 1.12-1.32), and 1.49 (95% CI: 1.20-1.86), respectively. The PPV of mRNA was 77.3% (95% CI, 59.8-94.8) in women aged 40 or older.
  
  
  CONCLUSIONS
  Women with negative cervical biopsy require follow-up before resumption of routine screening. Post-colposcopy HPV mRNA testing was as sensitive but more specific than post-colposcopy cytology. In addition, the HPV mRNA test showed higher PPV. A positive mRNA test post-colposcopy could justify treatment in women above 40 years.
authors: Department of Clinical Pathology, The University Hospital of North Norway, Tromsø, Norway.
authors: Sveinung Wergeland
authors: SW
authors: Sørbye
authors: Marc
authors: M
authors: Arbyn
authors: Silje
authors: S
authors: Fismen
authors: Tore Jarl
authors: TJ
authors: Gutteberg
authors: Elin Synnøve
authors: ES
authors: Mortensen
mesh_terms: D000328:Adult; D000368:Aged; D002584:Cervix Uteri / Q000473:pathology* / Q000821:virology*; D003127:Colposcopy; D003584:Cytological Techniques; D055088:Early Detection of Cancer / Q000379:methods*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D060787:Neoplasm Grading; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D027383:Papillomaviridae / Q000235:genetics* / Q000302:isolation & purification; D012333:RNA, Messenger / Q000032:analysis; D012367:RNA, Viral / Q000032:analysis*; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis / Q000473:pathology / Q000821:virology
chemical_list: D009856:Oncogene Proteins, Viral; D012333:RNA, Messenger; D012367:RNA, Viral