Molecular Biomarkers in Cervical Cytology: Screening and Triage

Abstract

Cervical cytological examination is a widely applied screening method for cervical cancer and its precursors. Liquid based cytology, besides produce good quality cervical cytology preparation, allows the use of ancillary laboratory techniques to improve the efficiency of cancer detection. Besides the commonly applied Human papilloma virus (HPV) tests, cervical cytology samples can also be used for genetic and epigentic studies such as mutation and gene promoter methylation analysis as well as assessment of telomerase activity. The ploidy of epithelial cells, the copy number and the expression of genes can also be assessed with an intact morphological background by immunocytochemistry and in situ hybridization. p16 immunocytochemical study on liquid based cytology has been reported to have a high positive predictive value in detection of cancer cells and their precursors.We have earlier applied chromosome in situ hybridization (ISH) as well as Ki-67 and telomerase immunocytochemistry in liquid based cervical cytology as attempts to assist the detection of carcinoma cells and high grade squamous intraepithelial lesions (HGSIL). Recently, we reported p63 and p73 immunocytochemistry to be potential good markers for detection of carcinoma and HGSIL in cervical cytology samples from screening population. Significantly higher p63 and p73 indices were found in HGSIL or carcinoma. Among atypical squamous cells of undetermined significance (ASC-US) and LGSIL, p63 and p73 indices of cases that subsequently progressed to HGSIL were significantly higher than those that did not. p63 and p73 immunocytochemistry was therefore useful for triage management of women with ASC-US and LGSIL. Amplification or deletion of genes has been identified in cervical cancers and their precursors by comparative genomic hybridization, real time PCR and ISH. Actually, evaluation of copy number of such candidate genes can be applied in cervical cytology samples by in situ hybridization. Combined cytopathologic evaluation and application of molecular markers in cervical cytology can facilitate reliable detection of cervical cancer and to allow triage of equivocal diagnoses based on a single clinical collection.