title: HPV mRNA is more specific than HPV DNA in triage of women with minor cervical lesions.
abstract: BACKGROUND
  In Norway, repeat cytology and HPV testing comprise delayed triage of women with minor cytological lesions. The objective of this study was to evaluate HPV DNA and HPV mRNA testing in triage of women with an ASC-US/LSIL diagnosis.
  
  
  METHODS
  We used repeat cytology, HPV DNA testing (Cobas 4800) and HPV mRNA testing (PreTect HPV-Proofer) to follow up 311 women aged 25-69 years with ASC-US/LSIL index cytology.
  
  
  RESULTS
  Of 311 women scheduled for secondary screening, 30 women (9.6%) had ASC-H/HSIL cytology at triage and 281 women (90.4%) had ASC-US/LSIL or normal cytology. The HPV DNA test was positive in 92 (32.7%) of 281 instances, and 37 (13.2%) were mRNA positive. Of the 132 women with repeated ASC-US/LSIL, we received biopsies from 97.0% (65/67) of the DNA-positive and 92.9% (26/28) of the mRNA-positive cases. The positive predictive values for CIN2+ were 21.5% (14/65) for DNA positive and 34.6% (9/26) for mRNA positive (ns). The odds ratio for being referred to colposcopy in DNA-positive cases were 2.8 times (95% CI: 1.8-4.6) higher that of mRNA-positive cases. Compared to the mRNA test, the DNA test detected four more cases of CIN2 and one case of CIN3.
  
  
  CONCLUSIONS
  The higher positivity rate of the DNA test in triage leads to higher referral rate for colposcopy and biopsy, and subsequent additional follow-up of negative biopsies. By following mRNA-negative women who had ASC-US/LSIL at triage with cytology, the additional cases of CIN2+ gained in DNA screening can be discovered. Our study indicates that in triage of repeated ASC-US/LSIL, HPV mRNA testing is more specific and is more relevant in clinical use than an HPV DNA test.
authors.affiliation: Department of Clinical Pathology, University Hospital of North Norway, Tromsø, Norway; Department of Medical Biology, Faculty of Health Sciences, The Arctic University of Norway, Tromsø, Norway.
authors.forename: Sveinung Wergeland
authors.initials: SW
authors.lastname: Sørbye
authors.affiliation: Department of Clinical Pathology, University Hospital of North Norway, Tromsø, Norway.
authors.forename: Silje
authors.initials: S
authors.lastname: Fismen
authors.affiliation: Department of Medical Biology, Faculty of Health Sciences, The Arctic University of Norway, Tromsø, Norway; Department of Microbiology and Infection Control, University Hospital of North Norway, Tromsø, Norway.
authors.forename: Tore Jarl
authors.initials: TJ
authors.lastname: Gutteberg
authors.affiliation: Department of Clinical Pathology, University Hospital of North Norway, Tromsø, Norway; Department of Microbiology and Infection Control, University Hospital of North Norway, Tromsø, Norway.
authors.forename: Elin Synnøve
authors.initials: ES
authors.lastname: Mortensen
authors.affiliation: Institute of Clinical Medicine, The Arctic University of Norway, Tromsø, Norway.
authors.forename: Finn Egil
authors.initials: FE
authors.lastname: Skjeldestad
mesh_terms: D000328:Adult; D000368:Aged; D065309:Atypical Squamous Cells of the Cervix / Q000473:pathology*; D004279:DNA, Viral / Q000235:genetics*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009664:Norway; D027383:Papillomaviridae / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D065310:Squamous Intraepithelial Lesions of the Cervix / Q000175:diagnosis* / Q000473:pathology; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D014218:Triage / Q000379:methods*
chemical_list: D004279:DNA, Viral; D012333:RNA, Messenger