title: Triage of women with ASCUS and LSIL cytology: use of qualitative assessment of p16INK4a positive cells to identify patients with high-grade cervical intraepithelial neoplasia.
abstract: BACKGROUND
  The identification of a small percentage of high-grade cervical intraepithelial neoplasias (HGCIN) among patients with minor cytological abnormalities (atypical squamous cells of undetermined significance [ASCUS] and/or low-grade squamous intraepithelial lesions [LSIL] group) is a major problem in cytology-based cervical cancer screening. The authors investigated the efficacy of p16INK4a as a biomarker to identify samples of patients with HGCIN among those with an ASCUS or LSIL result in Papanicolaou cytology.
  
  
  METHODS
  Consecutive liquid-based cytology specimens of 137 ASCUS and 88 LSIL results were selected from gynecologists who adopted a triage regimen with biopsy under colposcopy 2 months later, independent of the p16INK4a result. p16INK4a stained slides were prepared and independently read by 2 observers, who used a recently described score to categorize p16INK4a stained squamous cells. The endpoint of the study was detection of a biopsy-confirmed HGCIN.
  
  
  RESULTS
  The overall sensitivity and specificity of p16INK4a positive cells with a nuclear score >2 for diagnosis of HGCIN in ASCUS and LSIL cases combined was 96% and 83%, respectively. The sensitivity and specificity in the ASCUS group was 95% and 84%, and 100% and 81% in the LSIL group, respectively. Two observers had a high concordance in assessing p16INK4a stained cells (kappa value of 0.841).
  
  
  CONCLUSIONS
  These data suggested that the use of p16INK4a as a biomarker combined with nuclear scoring of p16INK4a positive cells in cervical cytology to triage ASCUS and/or LSIL cases allows identification of HGCIN with good sensitivity and specificity.
authors.affiliation: Department of Applied Tumor Biology, Institute of Pathology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Wentzensen
authors.forename: Christine
authors.initials: C
authors.lastname: Bergeron
authors.forename: Frederic
authors.initials: F
authors.lastname: Cas
authors.forename: Svetlana
authors.initials: S
authors.lastname: Vinokurova
authors.forename: Magnus
authors.initials: M
authors.lastname: von Knebel Doeberitz
mesh_terms: D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D002278:Carcinoma in Situ / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D005260:Female; D006801:Humans; D008403:Mass Screening / Q000379:methods; D008875:Middle Aged; D018307:Neoplasms, Squamous Cell / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D015588:Observer Variation; D012680:Sensitivity and Specificity; D014218:Triage / Q000379:methods*; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16