title: Triaging Atypical Squamous Cells-Cannot Exclude High-Grade Squamous Intraepithelial Lesion With p16/Ki67 Dual Stain.
abstract: OBJECTIVE
  The management of women with Pap cytology results categorized as "atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion" (ASC-H) can often be challenging. We assessed the performance of p16/Ki67 dual-stained cytology as a potential triage tool for the detection of biopsy-confirmed high-grade squamous intraepithelial lesions (HSILs) in women with ASC-H.
  
  
  METHODS
  Women with ASC-H were followed for a period of 36 months by repeat cytology and colposcopy. p16/Ki67 dual staining was performed retrospectively on the initial Pap cytology slide with ASC-H interpretation. Results were compared with the final histological diagnosis and/or cytological follow-up for at least 1 year. All outcomes were defined as clinically significant at the threshold of HSIL (cervical intraepithelial neoplasia grade 2 or worse).
  
  
  RESULTS
  One hundred sixty-nine cases fulfilled all conditions to be included in the study group. The rate of histologically confirmed HSIL was 57.4%, low-grade squamous intraepithelial lesion was diagnosed in 17.7% of the patients and normal histology or follow-up in 24.9% of the patients. Overall sensitivity and specificity of p16/Ki67 dual stain were 95% and 72%, respectively. Overall positive likelihood ratio of p16/Ki67 in detection of HSIL was 3.41, considerably increasing pretest probability from 57% to posttest probability of 82%.
  
  
  CONCLUSIONS
  A substantial subset of patients with ASC-H interpretations is associated with an appreciable risk of clinically significant cervical disease. p16/Ki67 dual stain can provide additional valuable information that may lead to higher-quality management of women with ASC-H, especially when initial colposcopy or biopsy results do not show HSIL lesions.
authors.affiliation: Department of Pathology and Cytology, Celje General Hospital, Celje, Slovenia.
authors.forename: Daja
authors.initials: D
authors.lastname: Šekoranja
authors.forename: Alenka
authors.initials: A
authors.lastname: Repše Fokter
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D065309:Atypical Squamous Cells of the Cervix; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis*; D003584:Cytological Techniques / Q000379:methods*; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis*; D008875:Middle Aged; D012189:Retrospective Studies; D065310:Squamous Intraepithelial Lesions of the Cervix / Q000175:diagnosis* / Q000628:therapy; D013194:Staining and Labeling / Q000379:methods*; D055815:Young Adult
chemical_list: C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D019394:Ki-67 Antigen