title: Utility of P16 expression and Ki-67 proliferation index in ASCUS and ASC-H pap tests.
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.
authors.affiliation: Division of Cytopathology, Department of Pathology, The Johns Hopkins Hospital, Baltimore, Maryland.
authors.forename: Adam D
authors.initials: AD
authors.lastname: Toll
authors.forename: Deidra
authors.initials: D
authors.lastname: Kelly
authors.forename: Zahra
authors.initials: Z
authors.lastname: Maleki
mesh_terms: D000328:Adult; D065309:Atypical Squamous Cells of the Cervix; D049109:Cell Proliferation; D002584:Cervix Uteri / Q000473:pathology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism*; D008875:Middle Aged; D065006:Papanicolaou Test; D030361:Papillomavirus Infections / Q000175:diagnosis* / Q000378:metabolism; D065310:Squamous Intraepithelial Lesions of the Cervix / Q000175:diagnosis* / Q000378:metabolism / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D055815:Young Adult
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D019394:Ki-67 Antigen
keywords: ASC-H; ASCUS; HR-HPV; Ki-67; P16