Correlation of CXCL12 expression and FoxP3+ cell infiltration with human papillomavirus infection and clinicopathological progression of cervical cancer.

Human cervical cancer is an immunogenic tumor with a defined pattern of histopathological and clinical progression. Tumor-infiltrating T cells contribute to immune control of this tumor; however, cervical cancer dysregulates this immune response both through its association with human papillomavirus (HPV) infection and by producing cytokines and chemokines. Animal tumor models have revealed associations between overproduction of the chemokine stromal cell-derived factor-1 (SDF-1 or CXCL12) and dysregulation of tumor-specific immunity. We therefore proposed that CXCL12 expression by cervical precancerous and cancerous lesions correlates with histopathological progression, loss of immune control of the tumor, and HPV infection. We found a significant association between cancer stage and CXCL12 expression for squamous and glandular lesions as well as with the HPV16+ (high-risk) status of the neoplastic lesions. Cancer progression was correlated with increasing levels of FoxP3 T-cell infiltration in the tumor. FoxP3 and CXCL12 expression significantly correlated for squamous and glandular neoplastic lesions. These observations were supported by enzyme-linked immunosorbent assay and Western blotting. In addition, we demonstrated CXCL12 expression by dyskaryotic cells in ThinPrep cervical smears. This study robustly links increased CXCL12 expression and FoxP3(+)-cell infiltration to HPV infection and progression of cervical cancer. It supports the detection of CXCL12 in cervical smears and biopsies as an additional biomarker for this disease.

Evaluation of NMP179 for the detection of squamous intraepithelial neoplasia in ThinPrep cervical slides using a combination of double immunostaining and morphometric methods of analysis.

This study investigates the potential value of the nuclear matrix protein NMP179 as a marker of abnormal squamous cells in ThinPrep slides. Forty-six cervical scrapes were collected as cell suspensions and ThinPrep slides were prepared. They were double-immunostained for NMP179 and Cytokeratin 18 (CK18), an endocervical cell marker. The method of analysis adopted for the study was designed to distinguish the abnormal squamous cells from benign epithelial cell so that the percentages of abnormal squamous cells that expressed the marker could accurately be determined. Initially, an attempt was made to identify benign and abnormal cells in the ThinPrep slides on the basis of their morphology and immunostaining patterns. Discrimination between the various types of epithelial cells was incomplete using this approach and a more precise method of discrimination between the different epithelial cell types was carried out using a combination of double immunostaining (NMP179 and CK18) and morphometry using nuclear area and nuclear cytoplasmic ratios. Once the different epithelial cell types had been identified, the specificity and sensitivity of NMP179 were determined. The optimal sensitivity (89.9%) was achieved at the N/C ratio 0.36; however, the specificity of NMP179 was very low for all N/C ratios and ranged from 38.8% to 42.2%.

Video monitoring of smear-taking at colposcopy: relationship to cytology.

OBJECTIVE: To investigate the reasons why cervical smears occasionally fail to reflect the underlying pathology in the cervix even when the smear is taken at colposcopy. DESIGN: A randomised study of three different smear-taking devices. SETTING: A colposcopy clinic. POPULATION: Women attending the colposcopy clinic. METHODS: A smear was taken from 172 nulliparous and 100 multiparous women at colposcopy and the procedure was monitored on a video-imaging system. The cytological findings were compared with the biopsy report in 147 nulliparous and 85 multiparous women. MAIN OUTCOME MEASURES: Accuracy of cytology and the effect of a range of variables on the accuracy of cytology. RESULTS: Sampling of the transformation zone was incomplete in 15% of nulliparous women and 8% of multiparous women. Univariate analysis of a range of variables including parity, type of sampling devices, completeness of sampling of the transformation zone, size of the transformation zone, size of the lesion (aceto-white area) and location of the squamo-columnar junction showed that the accuracy of cytology was influenced by all these factors except for parity and smear-taking devices. Multivariate analysis showed that the location of the squamo-columnar junction, the size of the transformation zone area, the size of the aceto-white area and the ratio of the aceto-white area to the area of the transformation zone influenced the accuracy of cytology. CONCLUSIONS: Women with large transformation zone areas (>30.03 mm(2)) and/or small aceto-white lesions (<7.01 mm(2)) are more likely to have an inaccurate cytology reports than women with small transformation zone and women with larger aceto-white areas. A ratio of the aceto-white area to the area of the transformation zone of 0.22 or less increases the risk of disagreement between the cytological and histological findings.