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Utility of P16 expression and Ki‐67 proliferation index in ASCUS and ASC‐H pap tests
Authors:Adam D. Toll M.D.  Deidra Kelly C.T.  Zahra Maleki M.D.
Affiliation:Division of Cytopathology, Department of Pathology, The Johns Hopkins Hospital, Baltimore, Maryland
Abstract: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. © 2013 Wiley Periodicals, Inc.
Keywords:ASCUS  ASC‐H  Ki‐67  P16  HR‐HPV
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