[404] What Is the Optimal Number of CINtec® PLUS Positive Cells for Detection of High Grade Cervical Intraepithelial Neoplasia?

Sanam Loghavi, Ann E Walts, Fai Chung, Shikha Bose. Cedars-Sinai Medical Center, Los Angeles, CA

Background: p16 and ki67 have each been shown to be good biomarkers for high grade cervical intraepithelial neoplasia (HG CIN). Recently CINtec® PLUS (CINtec), a dual immunostain for p16 and ki67, has been proposed as a tool for the triage of women with atypical squamous cells of undetermined significance (ASC) and/or low grade squamous intraepithelial lesions (LSIL) on Pap smear. Based on the manufacturer's guidelines the presence of ≥1 CINtec positive cell is interpreted as a positive test result. This retrospective study was designed to determine whether increasing the threshold for a positive result improves the test utility for detecting an underlying or subsequent HG CIN.
Design: 152 cervical SurePath Pap smears (87 ASC and 65 LSIL) with histological and/or cytological follow up (range 1 to 83 mos; median 10 mos) were retrieved from our departmental files. The Pap stained slides were destained and then immunostained utilizing the CINtec®PLUS Kit (mtm laboratories, Inc Westborough, MA) that detects over-expression of p16 and ki67 as brown/cytoplasmic and red/nuclear reaction products, respectively. p16 or ki67 staining alone was recorded as negative. CINtec positive cells were counted in each smear and the cases were classified into four groups (A: 0 + cells, B: ≥1 + cell, C: ≥5 + cells, D: ≥10 + cells). Sensitivity, specificity, and positive and negative predictive values for detecting an underlying or subsequent HG CIN were calculated for each group.
Results: The correlation between the number of CINtec positive cells and detection of HG CIN in ASC and LSIL Pap smears is shown in the tables below.

ASC (N=87)
Number of CINtec + cellsSensitivitySpecificityPPV*NPV*
≥ 162.5%67.1%16.1%94.6%
≥ 550%82.2%22.2%94.2%
≥ 1037.5%90.0%27.3%93.4%

LSIL (N=65)
Number of CINtec + cellsSensitivitySpecificityPPV*NPV*
≥ 171.4%47.1%27.0%85.7%
≥ 535.7%66.7%22.7%79.1%
≥ 1028.6%84.3%33.3%81.1%
* PPV: positive predictive value, NPV: negative predictive value

Conclusions: Increasing the threshold number of CINtec® PLUS positive cells required for a positive test result increases the specificity of the test significantly without sacrificing the negative predictive value.
A prospective study is warranted to confirm our results.
Category: Cytopathology

Tuesday, March 1, 2011 9:30 AM

Poster Session III # 94, Tuesday Morning


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