title: HPV mRNA testing in triage of women with ASC-US cytology may reduce the time for CIN2+diagnosis compared with repeat cytology.
abstract: BACKGROUND
  In delayed HPV triage women with atypical squamous cells of uncertain significance (ASC-US) cytology are retested after 6-12 months in order to decide whether they should be referred for colposcopy, further follow-up cytology or routine screening in three years. Triage using a specific HPV E6/E7 mRNA test may reduce referrals for colposcopy of women with ASC-US cytology compared to HPV DNA testing. We explored whether HPV mRNA triaging could reduce the time from ASC-US index cytology to biopsy compared with repeat cytology, and whether the positive predictive value (PPV) of the HPV mRNA test for high grade cervical intraepithelial neoplasia (CIN2+) was comparable with the PPV of repeat cytology.
  
  
  METHODS
  We used repeat cytology and the HPV mRNA test PreTect HPV-Proofer, which detects E6/E7 mRNA from HPV subtypes 16, 18, 31, 33 and 45, in the triage of women with ASC-US. We included all women from the two northernmost counties of Norway with a first ASC-US cytology during the period 2004-2008. Two triage methods were evaluated 1) only repeat cytology (n=964) and 2) both HPV mRNA testing and cytology (n=542). Histologically confirmed CIN2+ was the study endpoint.
  
  
  RESULTS
  Among 1506 women with an ASC-US index cytology, 59 women (3.9%) had biopsy taken, of whom 49 women had CIN2+ (PPV 83.1%). The mean time from index ASC-US cytology until the case was resolved (biopsy or return to screening) was 10.6 months in the repeat cytology group and 7.3 months in the HPV group (P < 0.001). Of the 964 women in the group with repeat cytology only, 35 women (3.6%) had biopsy and 30 had CIN2+ (PPV 85.7%). Of the 542 women in the group with both HPV test and cytology, 24 women (4.4%) had biopsy and 19 had CIN2+ (PPV 79.2%).
  
  
  CONCLUSIONS
  In triage of women with ASC-US, the HPV mRNA test significantly reduced the time from the first abnormal cytology until biopsy and had predictive values comparable with those of repeat cytology.
authors.affiliation: Department of Clinical Pathology, University Hospital of North Norway, 9038 Tromsø, Norway. sveinung.sorbye@unn.no
authors.forename: Sveinung Wergeland
authors.initials: SW
authors.lastname: Sørbye
authors.forename: Silje
authors.initials: S
authors.lastname: Fismen
authors.forename: Tore Jarl
authors.initials: TJ
authors.lastname: Gutteberg
authors.forename: Elin Synnøve
authors.initials: ES
authors.lastname: Mortensen
authors.forename: Finn Egil
authors.initials: FE
authors.lastname: Skjeldestad
mesh_terms: D000328:Adult; D052685:Alphapapillomavirus / Q000235:genetics*; D005260:Female; D006801:Humans; D011230:Precancerous Conditions / Q000175:diagnosis* / Q000821:virology; D012333:RNA, Messenger / Q000235:genetics*; D014218:Triage; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000821:virology
chemical_list: D012333:RNA, Messenger