scholarly journals Performance of DNA methylation assays for detection of high-grade cervical intraepithelial neoplasia (CIN2+): a systematic review and meta-analysis

2019 ◽  
Vol 121 (11) ◽  
pp. 954-965 ◽  
Author(s):  
Helen Kelly ◽  
Yolanda Benavente ◽  
Miquel Angel Pavon ◽  
Silvia De Sanjose ◽  
Philippe Mayaud ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cervical Intraepithelial Neoplasia ◽  
Meta Analysis ◽  
Intraepithelial Neoplasia ◽  
Relative Sensitivity ◽  
High Grade ◽  
Abnormal Cytology ◽  
Random Effects Models ◽  
Relative Specificity ◽  
Sensitivity Specificity

Abstract Background To conduct a meta-analysis of performance of DNA methylation in women with high-grade cervical intraepithelial neoplasia (CIN2+). Methods Medline and Embase databases were searched for studies of methylation markers versus histological endpoints. Pooled sensitivity, specificity and positive predictive value (PPV) for CIN2+ were derived from bivariate models. Relative sensitivity and specificity for CIN2+ compared to cytology and HPV16/18 genotyping were pooled using random-effects models. Results Sixteen thousand three hundred thirty-six women in 43 studies provided data on human genes (CADM1, MAL, MIR-124-2, FAM19A4, POU4F3, EPB41L3, PAX1, SOX1) and HPV16 (L1/L2). Most (81%) studies evaluated methylation assays following a high-risk (HR)-HPV-positive or abnormal cytology result. Pooled CIN2+ and CIN3+ prevalence was 36.7% and 21.5%. For a set specificity of 70%, methylation sensitivity for CIN2+ and CIN3+ were 68.6% (95% CI: 62.9–73.8) and 71.1% (95% CI: 65.7–76.0) and PPV were 53.4% (95% CI: 44.4–62.1) and 35.0% (95% CI: 28.9–41.6). Among HR-HPV+ women, the relative sensitivity of methylation for CIN2+ was 0.81 (95% CI: 0.63–1.04) and 1.22 (95% CI: 1.05–1.42) compared to cytology of atypical squamous cells of undetermined significance, or greater (ASCUS+) and HPV16/18 genotyping, respectively, while relative specificity was 1.25 (95% CI: 0.99–1.59) and 1.03 (95% CI: 0.94–1.13), respectively. Conclusion DNA methylation is significantly higher in CIN2+ and CIN3+ compared to ≤CIN1. As triage test, DNA methylation has higher specificity than cytology ASCUS+ and higher sensitivity than HPV16/18 genotyping.

scholarly journals The PapilloCheck Assay for Detection of High-Grade Cervical Intraepithelial Neoplasia

2015 ◽  
Vol 53 (11) ◽  
pp. 3553-3559 ◽  
Author(s):  
Emma J. Crosbie ◽  
Andrew Bailey ◽  
Alex Sargent ◽  
Clare Gilham ◽  
Julian Peto ◽  
...  
Keyword(s):  
Cervical Intraepithelial Neoplasia ◽  
Cervical Screening ◽  
Intraepithelial Neoplasia ◽  
Relative Sensitivity ◽  
Population Based ◽  
Cervical Cytology ◽  
Low Grade ◽  
High Grade ◽  
Abnormal Cytology ◽  
Normal Cytology

Human papillomavirus (HPV) testing is used in primary cervical screening, as an adjunct to cervical cytology for the management of low grade abnormal cytology, and in a test of cure. PapilloCheck (Greiner Bio-One) is a PCR-based DNA microarray system that can individually identify 24 HPV types, including the 13 high-risk (HR) types identified by Hybrid Capture 2 (HC2). Here, we compare PapilloCheck with HC2 for the detection of high-grade cervical intraepithelial neoplasia (CIN2+) in a total of 8,610 cervical cytology samples from the ARTISTIC population-based cervical screening study. We performed a retrospective analysis of 3,518 cytology samples from round 1 ARTISTIC enriched for underlying CIN2+ (n= 723) and a prospective analysis of 5,092 samples from round 3 ARTISTIC. Discrepant results were tested using the Roche reverse line blot (RLB) or Linear Array (LA) assay. The relative sensitivity and specificity of HR PapilloCheck compared with that of HC2 for the detection of CIN2+ in women aged over 30 years were 0.94 (95% confidence interval [CI], 0.91, 0.97) and 1.05 (95% CI, 1.04, 1.05), respectively. HC2 missed 44/672 (7%) CIN2+ lesions, while HR PapilloCheck missed 74/672 (11%) CIN2+ lesions. Thirty-six percent of HC2-positive normal cytology samples were HR HPV negative by both PapilloCheck and RLB/LA, indicating that the use of HR PapilloCheck rather than HC2 in population-based primary screening would reduce the number of additional tests required (e.g., reflex cytology) in women where underlying CIN2+ is extremely unlikely. HR PapilloCheck could be a suitable HPV detection assay for use in the cervical screening setting.

scholarly journals Identification of Circulating MicroRNAs as a Promising Diagnostic Biomarker for Cervical Intraepithelial Neoplasia and Early Cancer: A Meta-Analysis

2020 ◽  
Vol 2020 ◽  
pp. 1-14 ◽  
Author(s):  
Yao Jiang ◽  
Zuohong Hu ◽  
Zhihua Zuo ◽  
Yiqin Li ◽  
Fei Pu ◽  
...  
Keyword(s):  
Cervical Intraepithelial Neoplasia ◽  
Likelihood Ratio ◽  
Meta Analysis ◽  
Precancerous Lesion ◽  
Positive Likelihood Ratio ◽  
Negative Likelihood Ratio ◽  
Intraepithelial Neoplasia ◽  
Diagnostic Biomarker ◽  
Diagnostic Efficacy ◽  
Sensitivity Specificity

Background. Cervical cancer (CC) is one of the most common female malignant tumors. And cervical intraepithelial neoplasia (CIN) is the precancerous lesion of CC, which can progress to invasive CC. MicroRNAs (miRNAs) have been found to be potential diagnostic biomarkers for CIN or CC. However, recently, the lack of sufficient studies about the diagnostic value of miRNAs for CIN made it challenging to separately investigate the diagnostic efficacy of miRNAs for CIN. Likewise, the conclusions among those studies were discordant. Therefore, we conducted this meta-analysis, aimed at evaluating the diagnostic efficacy of miRNAs for CIN and CC patients. Methods. Literature search was performed in PubMed, Embase, and Web of Science databases. Pooled sensitivity, specificity, and other diagnostic parameters were calculated through Stata 14.0 software. Furthermore, subgroup analyses and metaregression analysis were conducted to explore the main sources of heterogeneity. Results. Ten articles covering 50 studies were eligible, which included 5,908 patients and 4,819 healthy individuals. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) were 0.81 (95% CI, 0.77-0.85), 0.86 (95% CI, 0.83-0.89), 5.9 (95% CI, 4.5-7.7), 0.22 (95% CI, 0.17-0.28), 27 (95% CI, 17-44), and 0.91 (95% CI, 0.88-0.93), respectively. Additionally, the ethnicity and internal reference were the main sources of heterogeneity. Conclusions. Circulating miRNAs can be a promising noninvasive diagnostic biomarker for CIN and early CC, especially miR-9 and miR-205, which need to be verified by large-scale studies.

scholarly journals Natural history of histologically confirmed high-grade cervical intraepithelial neoplasia during pregnancy: meta-analysis

BMJ Open ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. e048055
Author(s):  
Cheng Chen ◽  
Yu Xu ◽  
Wu Huang ◽  
Yi Du ◽  
Cui Hu
Keyword(s):  
Natural History ◽  
Cervical Intraepithelial Neoplasia ◽  
Meta Analysis ◽  
Intraepithelial Neoplasia ◽  
Progression Rate ◽  
Lower Grade ◽  
High Grade ◽  
Regression Rate ◽  
Persistence Rate ◽  
History Of

ObjectivesThis study aimed to conduct a meta-analysis of estimates of the natural history of high-grade cervical intraepithelial neoplasia (CIN) during pregnancy.SettingStudies examining the clinical courses of histologically confirmed high-grade CIN during pregnancy.ParticipantsWe searched PubMed, Web of Science and Embase for eligible studies. Studies were included if they reported the data regarding the natural history of histologically confirmed high-grade CIN during pregnancy. Final estimates were from the meta-analysis of 10 eligible studies.Primary outcome measuresThe regression rate, persistence rate and progression rate of histologically proven untreated high-grade CIN during pregnancy.ResultsA total of 10 original studies were included in this meta-analysis. During pregnancy, the regression rate, persistence rate and progression rate of high-grade CIN were 40% (95% CI 35% to 45%), 59% (95% CI 54% to 64%) and 1% (95% CI 0% to 2%), respectively. There was moderate heterogeneity among the studies. The results of the subgroup meta-analysis show that the pooled rates of regression and persistence during pregnancy were 59% (95% CI 54% to 65%) and 40% (95% CI 35% to 45%) for CIN2, and 29% (95% CI 25% to 33%) and 70% (95% CI 65% to 73%) for CIN3.ConclusionsDuring pregnancy, the majority of histologically confirmed high-grade CIN would be persistent or regressed to lower grade CIN or normal. However, it is still worth noting that a small percentage of high-grade CIN would progress to cervical cancer during pregnancy.

scholarly journals Evaluation of the Clinical Performance of the HPV-Risk Assay Using the VALGENT-3 Panel

2017 ◽  
Vol 55 (12) ◽  
pp. 3544-3551 ◽  
Author(s):  
N. J. Polman ◽  
A. Oštrbenk ◽  
L. Xu ◽  
P. J. F. Snijders ◽  
C. J. L. M. Meijer ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Screening ◽  
Cervical Cancer Screening ◽  
Clinical Performance ◽  
Intraepithelial Neoplasia ◽  
Relative Sensitivity ◽  
Hpv Testing ◽  
Abnormal Cytology ◽  
Cervical Intraepithelial Neoplasia Grade ◽  
Relative Specificity

ABSTRACTHuman papillomavirus (HPV) testing is increasingly being incorporated into cervical cancer screening. The Validation of HPV Genotyping Tests (VALGENT) is a framework designed to evaluate the clinical performance of various HPV tests relative to that of the validated and accepted comparator test in a formalized and uniform manner. The aim of this study was to evaluate the clinical performance of the HPV-Risk assay with samples from the VALGENT-3 panel and to compare its performance to that of the clinically validated Hybrid Capture 2 assay (HC2). The VALGENT-3 panel comprises 1,300 consecutive samples from women participating in routine cervical cancer screening and is enriched with 300 samples from women with abnormal cytology. DNA was extracted from original ThinPrep PreservCyt medium aliquots, and HPV testing was performed using the HPV-Risk assay by investigators blind to the clinical data. HPV prevalence was analyzed, and the clinical performance of the HPV-Risk assay for the detection of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) and CIN2 or worse (CIN2+) relative to the performance of HC2 was assessed. The sensitivity of the HPV-Risk assay for the detection of CIN3+ was similar to that of HC2 (relative sensitivity, 1.00; 95% confidence interval [CI], 0.95 to 1.05;P= 1.000), but the specificity of the HPV-Risk assay was significantly higher than that of HC2 (relative specificity, 1.02; 95% CI, 1.01 to 1.04;P< 0.001). For the detection of CIN2+, similar results were obtained, with the relative sensitivity being 0.98 (95% CI, 0.93 to 1.02;P= 0.257) and the relative specificity being 1.02 (95% CI, 1.01 to 1.03;P< 0.001). The performance of the HPV-Risk assay for the detection of CIN3+ and CIN2+ was noninferior to that of HC2, with allPvalues being ≤0.006. In conclusion, the HPV-Risk assay demonstrated noninferiority to the clinically validated HC2 by the use of samples from the VALGENT-3 panel for test validation and comparison.

scholarly journals Association between PEG3 DNA methylation and high-grade cervical intraepithelial neoplasia

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Claire Bosire ◽  
Adriana C. Vidal ◽  
Jennifer S. Smith ◽  
Dereje Jima ◽  
Zhiqing Huang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
North Carolina ◽  
Cervical Intraepithelial Neoplasia ◽  
Regression Models ◽  
Medical Center ◽  
Intraepithelial Neoplasia ◽  
Hpv Infection ◽  
High Grade ◽  
Logistic Regression Models ◽  
High Risk Hpv

Abstract Background Epigenetic mechanisms are hypothesized to contribute substantially to the progression of cervical intraepithelial neoplasia (CIN) to cervical cancer, although empirical data are limited. Methods Women (n = 419) were enrolled at colposcopic evaluation at Duke Medical Center in Durham, North Carolina. Human papillomavirus (HPV) was genotyped by HPV linear array and CIN grade was ascertained by biopsy pathologic review. DNA methylation was measured at differentially methylated regions (DMRs) regulating genomic imprinting of the IGF2/H19, IGF2AS, MESTIT1/MEST, MEG3, PLAGL1/HYMAI, KvDMR and PEG10, PEG3 imprinted domains, using Sequenom-EpiTYPER assays. Logistic regression models were used to evaluate the associations between HPV infection, DMR methylation and CIN risk overall and by race. Results Of the 419 participants, 20 had CIN3+, 52 had CIN2, and 347 had ≤ CIN1 (CIN1 and negative histology). The median participant age was 28.6 (IQR:11.6) and 40% were African American. Overall, we found no statistically significant association between altered methylation in selected DMRs and CIN2+ compared to ≤CIN1. Similarly, there was no significant association between DMR methylation and CIN3+ compared to ≤CIN2. Restricting the outcome to CIN2+ cases that were HR-HPV positive and p16 staining positive, we found a significant association with PEG3 DMR methylation (OR: 1.56 95% CI: 1.03–2.36). Conclusions While the small number of high-grade CIN cases limit inferences, our findings suggest an association between altered DNA methylation at regulatory regions of PEG3 and high grade CIN in high-risk HPV positive cases.

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