Abstract | BACKGROUND: Although previous studies have shown that p16(INK4a) and Ki-67 are sensitive and specific markers for high-grade lesions (≥CIN2) on cervical biopsies, limited information is available regarding the performance of a dual-staining approach as a diagnostic adjunct in cervical cytology. We evaluated a dual p16(INK4a)/Ki-67 immunocytochemistry (ICC) assay to determine its sensitivity and specificity versus that of high-risk HPV (HR-HPV) in a US-based pilot cytology study. METHODS: ThinPrep specimens from 122 cervical cytology specimens encompassing 23 negative (NILM), 20 ASC-US, 22 LSIL, 17 ASCH, 22 HSIL, and 18AGC cases were processed for multiplexed ICC staining using a CINtec Plus Kit. Dual-positive assay results were defined based on the detection of 1 or more epithelial cells that were stained for both p16INK4a and Ki-67 without regard to cellular morphology. HR-HPV testing was performed by multiplex PCR with capillary electrophoresis genotyping. RESULTS: Dual staining for p16(INK4a) and Ki-67 was frequently detected in HSIL and AGC but was rarely detected in NILM cases. The HR-HPV assay showed a sensitivity of 76.2% and a specificity of 55.8% for the detection of clinically significant cervical squamous or endometrial lesions. In contrast, the colocalization of p16(INK4a) plus Ki-67 maintained a high sensitivity of 81.8% and improved specificity to 81.8% for biopsy-confirmed CIN2/3, endocervical adenocarcinoma, or endometrial adenocarcinoma. CONCLUSIONS: Dual staining for p16(INK4a)/Ki-67 immunocytochemistry dramatically increased specificity and maintained high-level sensitivity for the diagnosis of CIN2/3 or glandular lesions compared with PCR-based testing for HR-HPV.
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Authors | Meenakshi Singh, Daniel Mockler, Ali Akalin, Stephanie Burke, A Laurie Shroyer, Kenneth R Shroyer |
Journal | Cancer cytopathology
(Cancer Cytopathol)
Vol. 120
Issue 1
Pg. 26-34
(Feb 25 2012)
ISSN: 1934-6638 [Electronic] United States |
PMID | 22162342
(Publication Type: Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Cyclin-Dependent Kinase Inhibitor p16
- Ki-67 Antigen
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Topics |
- Adenocarcinoma
(diagnosis)
- Carcinoma, Squamous Cell
(diagnosis)
- Cyclin-Dependent Kinase Inhibitor p16
(analysis)
- Cytodiagnosis
- Early Detection of Cancer
(methods)
- Female
- Humans
- Immunohistochemistry
(methods)
- Ki-67 Antigen
(analysis)
- Multiplex Polymerase Chain Reaction
- Papillomavirus Infections
(diagnosis)
- Pilot Projects
- Sensitivity and Specificity
- Uterine Cervical Neoplasms
(diagnosis, virology)
- Uterine Cervical Dysplasia
(diagnosis)
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