Local immune response in the microenvironment of CIN2-3 with and without spontaneous regression

Fifteen to thirty percent of cases with histologically confirmed CIN2-3 in cervical biopsies regress spontaneously (ie, show CIN1 or less in the follow-up cervical cone). The balance between immune-reactive cells from the host and high-risk human papillomavirus (hrHPV) genotypes may provide a biological explanation for this phenomenon. We retrospectively studied 55 cases of CIN2-3 in a cervical biopsy with subsequent cervical cone to assess whether hrHPV genotypes (by AMPLICOR and Linear Array tests) CD4, CD8, CD25, CD138 and Foxp3 cells (by quantitative immunohistochemistry) in the cervical biopsies can predict regression (defined as CIN1 or less in the follow-up cone biopsy). Eighteen percent of the CIN2-3 cases regressed (median biopsy-cervical cone time interval: 12.0 weeks, range: 5.0-34.1 weeks). HPV-16 correlated with low CD8(+) and high CD25(+). None of the regressing CIN2-3 lesions contained HPV-16. The regressing CIN2-3 lesions had lower numbers of stromal CD138(+) and higher numbers of stromal CD8(+) cells; higher stromal and intra-epithelial ratios of CD4(+)/CD25(+) cells; higher ratios of CD8(+)/CD25(+) cells and lower ratios of CD8(+)/CD4(+), CD138(+)/Foxp3(+) and CD25(+)/Foxp3(+) cells in the stroma. With multivariate survival analysis, stromal CD8(+) cell numbers, CD4(+)/CD25(+) cell ratios and CD138(+) cell numbers are found to be independent regression predictors. In conclusion, in non-HPV-16 CIN2-3 lesions, assessing stromal immune cells can be a useful prognostic indicator of regression or persistence. Modern Pathology (2010) 23, 1231-1240; doi:10.1038/modpathol.2010.109; published online 28 May 201

Interaction of epithelial biomarkers, local immune response and condom use in cervical intraepithelial neoplasia 2-3 regression

Objective. Cervical intraepithelial neoplasia grades 2-3 (CIN2-3) are usually treated by cone excision, although only 30% progress to cancer and 6-50% regress spontaneously. Biomarkers predicting CIN2-3 regression would be of great clinical value and could reduce unnecessary cone excision and associated complications. The aim of this study was to investigate whether punch-biopsy derived immunohistochemical biomarkers, local immune response, CIN lesion size and condom use are independently correlated to regression of CIN2-3. Methods. A prospective population-based cohort study of 162 women aged 25-40, with first-time onset diagnosis of CIN2-3 in colposcopy-directed biopsies was carried out. The median biopsy-cone interval was 16 weeks. Regression was defined as CIN1 or less in the cone biopsy. Results. The regression rate was 21% (34/162). pRb>30% in the lower epithelial half was the strongest predictor for regression (30% regression, p 2.5 mm and CD4 + - strom