Modern biomarkers for precancerous lesions of the uterine cervix : Histological-cytological correlation and use

Abstract

The correlation between the cytological findings from the PAP smear and the histological outcome in cases where the cytological findings must be histologically verified, is an integral component of the German screening program for cervical cancer. These data are collected nationwide as part of abenchmarking process by the individual Associations of Statutory Health Insurance Physicians (KV) in the federal states and reported to the National Association of Statutory Health Insurance Physicians (KBV) in Berlin. In most cases there is agood correlation between cytology and histology but in some cases either adifferent grade of severity of cervical intraepithelial neoplasia (CIN) is found or the histological findings are negative. The reasons for alack of correlation can be insufficient sampling in the cytology or the biopsy or amisinterpretation of the individual findings. Although the findings from H&E sections are considered to be the gold standard in the histological evaluation, it has long been known that the interobserver agreement in these preparations is only moderate. Asignificant improvement becomes apparent, firstly by the classification of cervical cancer precursors into low-grade and high-grade groups and secondly by the targeted application of biomarkers, in particular p16 and Ki-67, according to the recommendations of the lower anogenital squamous terminology standardization (LAST) project. The biomarkers p16 and Ki-67 should be used in the differential diagnostics between reactive and reparative alterations and for further differentiation of a CIN grade 2 but not to confirm aCIN grade 3. It is still unclear whether p16 is suitable as aprognostic marker for low-grade lesions.