The utility of ThinPrep cytology and immunohistochemical staining of p16INK4a, Ki-67, and p63 in the assessment of cervical intraepithelial neoplasia (dysplasia)

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Cervical intraepithelial neoplasia (CIN) is a precancerous lesion with the capability of progressing to squamous-cell carcinoma (SCC). Despite the clearly defined criteria, histopathological diagnoses in hematoxylin and eosin-stained sections are subject to high rates of interpathologist discordance. The aim of this study was to compare and evaluate the results of both ThinPrep cytology and the immunohistochemical-staining pattern of p16, Ki-67, and p63, in diagnosing and grading cervical dysplasia. After such a comparison, the researchers hoped that the diagnostic accuracy in equivocal cases would improve.

Patients and methods

The current study was carried out on 38 patients with nondysplastic and neoplastic cervical lesions, and initial screening with ThinPrep cytology was performed. Immunohistochemical-staining of p16, Ki-67, and p63 was performed for all the patients. The results were compared with the histopathological diagnoses.


ThinPrep cytology was found to have 100% sensitivity in detecting low-grade and high-grade squamous intraepithelial lesions – with relatively low specificity – when compared with confirmed histopathological results. Diffuse, strong, band-like p16-immunostaining was detected in 71.4% of the CIN2 patients, 91.7% of the CIN3 patients, and 87.5% of the SCC patients, which were significantly associated with the CIN grade (P<0.001). Most of the CIN3 and SCC patients showed strong Ki-67 and p63 expression levels, with significant CIN-grade association (P<0.001 for both). A significant positive correlation was found between the expression levels of the three biomarkers.


ThinPrep cytology, with slightly high sensitivity but low specificity, can be useful as a screening method to detect CIN and SCC in patients. Also, p16 and Ki-67 are valuable diagnostic markers for cervical lesions, and the expression levels of p16, Ki-67, and p63 increase as the cervical-lesion grade is higher. Combined staining of these three studied biomarkers is thus useful for detecting and grading CIN, especially in problematical patients, for optimum management.

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