Utility of P16 expression and Ki-67 proliferation index in ASCUS and ASC-H pap tests

Adam D. Toll, Deidra Kelly, Zahra Maleki

Research output: Contribution to journalArticlepeer-review


Current cervical screening uses a combination of cytology and high-risk human papillomavirus (HR-HPV) analysis in cases of atypical squamous cells of undetermined significance (ASCUS) and atypical squamous cells cannot exclude high-grade intraepithelial lesion (ASC-H). These diagnoses are subject to interobserver variability and HR-HPV analysis can be limited by sampling inadequacy. This study correlates immunoexpression of P16 and Ki-67 in residual cervicovaginal material against cytology category and HR-HPV status. Eighteen pap tests were selected: 8 ASCUS, 4 ASC-H, and 6 controls (2 LSIL and 4 HSIL). Digene Hybrid Capture II test was used to detect HR-HPV. The cytospins were stained for P16/Ki-67. Pap tests, P16, Ki-67, HR-HPV result and available biopsies were correlated. P16 expression correlated with HR-HPV status in 15/17 cases. Discordant cases (1 ASCUS and 1 ASC-H) were +P16/-HR-HPV. Ki-67 correlated with HR-HPV in 8/15 cases. Discordant cases were +HR-HPV/- Ki-67 (HSIL, LSIL, and ASC-H one each), and -HR-HPV/+Ki-67 (3 ASCUS, 1 LSIL, 1 ASC-H). Two cases were?+?P16/+ Ki-67/- HR-HPV. None were - P16/- Ki-67/+ HR-HPV. Histologic follow-up in 13 cases varied from benign to CIN III. Two cases of +P16/ - Ki-67/- HR-HPV had benign cervical biopcies. Although a small sample size, our findings show a utility for adjunct P16/ Ki-67 in addition to HR-HPV testing in cases of squamous atypia when HR-HPVs are non-detected due to low DNA copies, or missed lesions in cervical biopsies. Diagn. Cytopathol. 2014;42:576-581.

Original languageEnglish (US)
Pages (from-to)576-581
Number of pages6
JournalDiagnostic cytopathology
Issue number7
StatePublished - Jul 2014
Externally publishedYes


  • ASC-H
  • HR-HPV
  • Ki-67
  • P16

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology


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