Dataset Information

Host cell DNA methylation markers for the detection of high-grade anal intraepithelial neoplasia and anal cancer.

ABSTRACT: High-grade anal intraepithelial neoplasia (AIN2/3; HGAIN) is highly prevalent in HIV+ men who have sex with men (MSM), but only a minority will eventually progress to cancer. Currently the cancer risk cannot be established, and therefore all HGAIN are treated, resulting in overtreatment. We assessed the potential of host cell DNA methylation markers for detecting HGAIN and anal cancer.Tissue samples of HIV+ men with anal cancer (n=26), AIN3 (n=24), AIN2 (n=42), AIN1 (n=22) and controls (n=34) were analyzed for DNA methylation of nine genes using quantitative methylation-specific-PCR. Univariable and LASSO logistic regression, followed by leave-one-out-cross-validation (LOOCV) were used to determine the performance for the detection of AIN3 and cancer.Methylation of all genes increased significantly with increasing severity of disease (p<2x10-6). HGAIN revealed a heterogeneous methylation pattern, with a subset resembling cancer. Four genes (ASCL1, SST, ZIC1 and ZNF582) showed remarkable performance for AIN3 and anal cancer detection (AUC>0.85). The most potent marker, ZNF582 (AUC=0.89), detected all cancers and 54% of AIN3 at 93% specificity. Slightly better performance (AUC=0.90) was obtained using a marker panel including five markers.DNA methylation is significantly associated with anal carcinogenesis. A methylation marker panel, including ZNF582, can identify anal cancer and HGAIN with a cancer-like methylation pattern. Validation studies are warranted to verify their potential for the screening and management of HIV+ MSM at risk for anal cancer.

SUBMITTER: van der Zee RP

PROVIDER: S-EPMC6424081 | biostudies-other | 2018 Jul

REPOSITORIES: biostudies-other

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Host Cell Deoxyribonucleic Acid Methylation Markers for the Detection of High-grade Anal Intraepithelial Neoplasia and Anal Cancer.

van der Zee Ramon P RP Richel Olivier O van Noesel Carel J M CJM Novianti Putri W PW Ciocanea-Teodorescu Iuliana I van Splunter Annina P AP Duin Sylvia S van den Berk Guido E L GEL Meijer Chris J L M CJLM Quint Wim G V WGV de Vries Henry J C HJC Prins Jan M JM Steenbergen Renske D M RDM

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20190301 7

<h4>Background</h4>High-grade anal intraepithelial neoplasia (AIN2/3; HGAIN) is highly prevalent in human immunodeficiency virus positive (HIV+) men who have sex with men (MSM), but only a minority will eventually progress to cancer. Currently, the cancer risk cannot be established, and therefore all HGAIN is treated, resulting in overtreatment. We assessed host cell deoxyribonucleic acid (DNA) methylation markers for detecting HGAIN and anal cancer.<h4>Methods</h4>Tissue samples of HIV+ men wit ...[more]

PMID: 30060049

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Project description:BackgroundVulval intraepithelial neoplasia (VIN) is a pre-malignant condition of the vulval skin; its incidence is increasing in women under 50 years. VIN is graded histologically as low grade or high grade. High grade VIN is associated with infection with human papilloma virus (HPV) infection and may progress to invasive disease. There is no consensus on the optimal management of high grade VIN. The high morbidity and high relapse rate associated with surgical interventions call for a formal appraisal of the evidence available for less invasive but effective interventions for high grade VIN.ObjectivesTo evaluate the effectiveness and safety of medical interventions for high grade VIN.Search strategyWe searched the Cochrane Gynaecological Cancer Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 3), MEDLINE and EMBASE (up to September 2010). We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field.Selection criteriaRandomised controlled trials (RCTs) that assessed medical interventions, in adult women diagnosed with high grade VIN.Data collection and analysisTwo review authors independently abstracted data and assessed risk of bias. Where possible the data were synthesised in a meta-analysis.Main resultsFour trials met our inclusion criteria: three assessed the effectiveness of topical imiquimod versus placebo in women with high grade VIN; one examined low versus high dose indole-3-carbinol in similar women. Meta-analysis of three trials found that the proportion of women who responded to treatment at 5 to 6 months was much higher in the group who received topical imiquimod than in the group who received placebo (relative risk (RR) = 11.95, 95% confidence interval (CI) 3.21 to 44.51). A single trial showed similar results at 12 months in (RR = 9.10, 95% CI 2.38 to 34.77). Only one trial reported adverse events, which were more common in the imiquimod group. One trial found no significant differences in quality of life (QoL) or body image between the imiquimod and placebo groups.Authors' conclusionsImiquimod appears to be effective, but its safety needs further examination. Its use is associated with side effects which are tolerable, but more extensive data on adverse effects are required. Long term follow-up should be mandatory in view of the known progression of high grade VIN to invasive disease. Alternative medical interventions, such as cidofovir, should be explored.

Dataset Information

Host cell DNA methylation markers for the detection of high-grade anal intraepithelial neoplasia and anal cancer.

Publications

Host Cell Deoxyribonucleic Acid Methylation Markers for the Detection of High-grade Anal Intraepithelial Neoplasia and Anal Cancer.

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