Analysis of performance characteristics of five cell cycle-related immunohistochemical markers and human papillomavirus genotyping in the diagnosis of cervical squamous cell carcinoma precursor lesions.

OBJECTIVE: To study the performance values of a set of five immunohistochemical markers involved in cell cycle regulation as a potential aid in the differential diagnosis between squamous intraepithelial lesions (SILs) and normal or benign conditions of the uterine cervix.

STUDY DESIGN: Results from immunohistochemical evaluation of p16, cyclin D1, p53, Ki67, and ProEx C markers and human papillomavirus genotyping were collected from a previous study performed on 37 normal or benign cervices, 39 low grade SILs and 73 high grade SILs. A multivariate analysis was used to examine the specific diagnostic value of each marker and to ascertain those most relevant for SIL diagnosis. For markers with good data fit, sensitivity, specificity, accuracy, area under the receiver operating characteristic curve, and integrated discrimination improvement, were calculated.

RESULTS: Among individual markers, ProEx C showed the best specificity; p16 displayed the highest sensitivity and area under receiver operating characteristic curve for SIL diagnosis. Integrated discrimination improvement demonstrated that the p16 plus ProEx C model has better discrimination capacity than p16 plus Ki67 or ProEx C plus Ki67.

CONCLUSION: Use of ProEx C alone or in combination with p16 could provide useful information for SIL diagnosis.