title: Triage of women with minor abnormal cervical cytology: meta-analysis of the accuracy of an assay targeting messenger ribonucleic acid of 5 high-risk human papillomavirus types.
abstract: BACKGROUND
  High-risk human papillomavirus (hrHPV) DNA detection is generally accepted for the triage of women with a cytologic diagnosis of atypical squamous cells of undetermined significance (ASC-US). However, no consensus has been reached on the optimal management of low-grade squamous intraepithelial lesions (LSIL).
  
  
  METHODS
  In this meta-analysis, the diagnostic accuracy of nucleic acid sequence-based amplification (NASBA) detection of messenger ribonucleic acid (mRNA) of 5 hrHPV types (the PreTect HPV-Proofer and NucliSENS EasyQ tests) for detecting grade 2 cervical intraepithelial neoplasia or worse (CIN2+) and CIN3+ was assessed in women who had a diagnosis of ASC-US and LSIL. The results were compared with the Hybrid Capture-2 (HC2) assay, which detects the DNA of 13 hrHPV types. A bivariate random-effect model that incorporated the intrinsic correlation between the true-positive and false-positive rates was used for a pooled meta-analysis.
  
  
  RESULTS
  Considering underlying CIN2+, the pooled absolute sensitivity of the 10 included studies was 75.4% (95% confidence interval [CI], 68.1%-82.7%) and 76.2% (95% CI, 68.3%-76.9%) for the triage of ASC-US and LSIL, respectively. The pooled absolute specificity to exclude CIN2+ was 77.9% (95% CI, 70.1%-85.7%) and 74.2% (95% CI, 69.5%-78.8%) in women with ASC-US and LSIL, respectively. Five studies allowed direct comparison of the mRNA assays with HC2. Considering CIN2+ in women with ASC-US and LSIL, mRNA testing was substantially more specific than the HC2 assay (ratio: 1.98 and 3.36, respectively; P < .001) but was less sensitive (ratio: 0.80 and 0.74, respectively; P < .001).
  
  
  CONCLUSIONS
  HPV assays for detecting the mRNA of 5 hrHPV types may reduce the over-diagnosis of women who have minor cytologic abnormalities. However, given the lower sensitivity, women with negative mRNA test results cannot be considered free of CIN2+ and require further surveillance.
authors.affiliation: Unit of Cancer Epidemiology, Scientific Institute of Public Health, Brussels, Belgium.
authors.forename: Freija
authors.initials: F
authors.lastname: Verdoodt
authors.forename: Anne
authors.initials: A
authors.lastname: Szarewski
authors.forename: Philippe
authors.initials: P
authors.lastname: Halfon
authors.forename: Kate
authors.initials: K
authors.lastname: Cuschieri
authors.forename: Marc
authors.initials: M
authors.lastname: Arbyn
mesh_terms: D000328:Adult; D055088:Early Detection of Cancer; D005260:Female; D006801:Humans; D008875:Middle Aged; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification; D030361:Papillomavirus Infections / Q000175:diagnosis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis* / Q000235:genetics; D012367:RNA, Viral / Q000032:analysis / Q000235:genetics; D012680:Sensitivity and Specificity; D014218:Triage / Q000379:methods*; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis / Q000821:virology*; D014626:Vaginal Smears; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis / Q000821:virology*
chemical_list: D012333:RNA, Messenger; D012367:RNA, Viral
keywords: HPV; atypical squamous cells of undetermined significance; cervical cancer; cervical intraepithelial neoplasia; diagnostic accuracy; human papillomavirus testing; low-grade squamous intraepithelial lesions; messenger RNA; meta-analysis; triage