Identification of high-grade cervical dysplasia by the detection of p16INK4a in cell lysates obtained from cervical samples.

Abstract:

BACKGROUND:Current cervical cancer screening approaches are based on cytology supplemented by human papillomavirus (HPV) testing in some settings. Whereas cytology is laborious and depends on the cytologists' experience, HPV testing has limited specificity when it is used to detect high-grade lesions. A dichotomous test to identify high-grade lesions with greater specificity may be a useful tool for cervical cancer screening. p16(INK4a) is a cell-cycle regulator that has demonstrated strong overexpression in cervical precancer cells and cervical cancer induced by the deregulated expression of HPV oncogenes. METHODS:The authors used a sandwich enzyme-linked immunosorbent assay (ELISA) to quantify the amount of solubilized p16(INK4a) protein in lysates that were prepared from cervical samples to detect high-grade cervical lesions. In total, 187 specimens that were obtained after sampling for conventional cytology in women who attended a cervical colposcopy clinic were analyzed. Seventy-six women underwent a biopsy, and 45 of those women showed histologically confirmed, high-grade cervical intraepithelial neoplasia. RESULTS:For 76 women with biopsy-proven diagnoses, receiver operating characteristic (ROC) analysis of different cutoff values showed an area under the ROC curve of 0.89 for the detection of high-grade cervical dysplasia. At a cutoff value of 8 U/mL, the sensitivity of the p16(INK4a) ELISA for detecting high-grade dysplastic cervical lesions was 96%. CONCLUSIONS:The data obtained in this study suggested that ELISA-based quantification of solubilized p16(INK4a) protein may have high sensitivity for detecting cervical precancer. Further population-based studies will be necessary to analyze the specificity and predictive values of p16(INK4a) protein quantification in cervical samples.

journal_name

Cancer

journal_title

Cancer

authors

Wentzensen N,Hampl M,Herkert M,Reichert A,Trunk MJ,Poremba C,Ridder R,von Knebel Doeberitz M

doi

10.1002/cncr.22247

subject

Has Abstract

pub_date

2006-11-01 00:00:00

pages

2307-13

issue

9

eissn

0008-543X

issn

1097-0142

journal_volume

107

pub_type

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