Consistent Condom Use Increases the Regression Rate of Cervical Intraepithelial Neoplasia 2-3

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. The aim of this study was to examine the influence of clinical factors like smoking habits, number of lifetime sexual partners, age at first sexual intercourse, sexual activity span and hormonal versus non-hormonal contraception type on the regression rate of CIN2-3.In this prospective population-based cohort study 170 women aged 25-40 with abnormal cytology and colposcopy-directed biopsies showing first time onset CIN2-3 were consecutively included. The interval between biopsy and cone excision was standardized to minimum 12 weeks. Regression was defined as ≤ CIN1 in the cone biopsy.The regression rate was 22%. Consistent condom use, defined as those women whose partners used condoms for all instances of sexual intercourse, was infrequent (n=20, 12%). In univariate analysis consistent condom use, hormonal contraception and age at first sexual intercourse significantly predicted regression. In a multivariate analysis only consistent condom use remained as an independent predictor of regression (regression rate 55%, p=0.001, hazard ratio=4.4).Consistent condom use between punch biopsy and cone excision in first-time onset CIN2-3 patients significantly increases the regression rate

Human papillomavirus testing versus repeat cytology for triage of minor cytological cervical lesions

Background: A typical squamous cells of undetermined significance (ASCUS) and low-grade squamous intra-epithelial lesions (LSIL) are minor lesions of the cervical epithelium, detectable by cytological examination of cells collected from the surface of the cervix of a woman. Usually, women with ASCUS and LSIL do not have cervical (pre-) cancer, however a substantial proportion of them do have underlying high-grade cervical intra-epithelial neoplasia (CIN, grade 2 or 3) and so are at increased risk for developing cervical cancer. Therefore, accurate triage of women with ASCUS or LSIL is required to identify those who need further management. This review evaluates two ways to triage women with ASCUS or LSIL: repeating the cytological test, and DNA testing for high-risk types of the human papillomavirus (hrHPV) - the main causal factor of cervical cancer. Objectives Main objective: To compare the accuracy of hrHPV testing with the Hybrid Capture 2 (HC2) assay against that of repeat cytology for detection of underlying cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) or grade 3 or worse (CIN3+) in women with ASCUS or LSIL. For the HC2 assay, a positive result was defined as proposed by the manufacturer. For repeat cytology, different cut-offs were used to define positivity: Atypical squamous cells of undetermined significance or worse (ASCUS+), low-grade squamous intra-epithelial lesions or worse (LSIL+) or high-grade squamous intra-epithelial lesions or worse (HSIL+). Secondary objective: To assess the accuracy of the HC2 assay to detect CIN2+ or CIN3+ in women with ASCUS or LSIL in a larger group of reports of studies that applied hrHPV testing and the reference standard (coloscopy and biopsy), irrespective whether or not repeat cytology was done. Search methods: We made a comprehensive literature search that included the Cochrane Register of Diagnostic Test Accuracy Studies; the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE (through PubMed), and EMBASE (last search 6 January 2011). Selected journals likely to contain relevant papers were handsearched from 1992 to 2010 (December). We also searched CERVIX, the bibliographic database of the Unit of Cancer Epidemiology at the Scientific Institute of Public Health (Brussels, Belgium) which contains more than 20,000 references on cervical cancer. More recent searches, up to December 2012, targeted reports on the accuracy of triage of ASCUS or LSIL with other HPV DNA assays, or HPV RNA assays and other molecular markers. These searches will be used for new Cochrane reviews as well as for updates of the current review. Selection criteria: Studies eligible for inclusion in the review had to include: women presenting with a cervical cytology result of ASCUS or LSIL, who had undergone both HC2 testing and repeat cytology, or HC2 testing alone, and were subsequently subjected to reference standard verification with colposcopy and colposcopy-directed biopsies for histologic verification. Data collection and analysis: The review authors independently extracted data from the selected studies, and obtained additional data from report authors. Two groups of meta-analyses were performed: group I concerned triage of women with ASCUS, group II concerned women with LSIL. The bivariate model (METADAS-macro in SAS) was used to assess the absolute accuracy of the triage tests in both groups as well as the differences in accuracy between the triage tests. Main results: The pooled sensitivity of HC2 was significantly higher than that of repeat cytology at cut-off ASCUS+ to detect CIN2+ in both triage of ASCUS and LSIL (relative sensitivity of 1.27 (95% CI 1.16 to 1.39; P value < 0.0001) and 1.23 (95% CI 1.06 to 1.4; P value 0.007), respectively. In ASCUS triage, the pooled specificity of the triage methods did not differ significantly from each other (relative specificity: 0.99 (95% CI 0.97 to 1.03; P value 0.98)). However, the specificity of HC2 was substantially, and significantly, lower than that of repeat cytology in the triage of LSIL (relative specificity: 0.66 (95% CI 0.58 to 0.75) P value < 0.0001). Authors' conclusions: HPV-triage with HC2 can be recommended to triage women with ASCUS because it has higher accuracy (significantly higher sensitivity, and similar specificity) than repeat cytology. When triaging women with LSIL, an HC2 test yields a significantly higher sensitivity, but a significantly lower specificity, compared to a repeat cytology. Therefore, practice recommendations for management of women with LSIL should be balanced, taking local circumstances into account

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&gt;30% in the lower epithelial half was the strongest predictor for regression (30% regression, p 2.5 mm and CD4 + - strom