Dataset Information

Evaluation of CIN2/3 Lesion Regression in GynTect^® DNA Methylation-Marker-Negative Patients in a Longitudinal Study.

ABSTRACT: Cervical intraepithelial neoplasia (CIN) grade 2/3 has a high spontaneous regression rate, especially among women ≤29 years of age. To reduce overtreatment, reliable prognostic biomarkers would be helpful. The main aim of this study was to analyze the negative predictive value of the methylation marker panel GynTect^® for lesion regression. In this prospective, multicenter, longitudinal observational proof-of-concept study, women aged ≤29 years with histologically confirmed CIN2 (n = 24) or CIN3 (n = 36) were closely monitored without treatment for up to 24 or 12 months, respectively. The outcome was either regression, persistence, or progression of the lesion. For each patient, a single baseline sample (V0) for cytology, hrHPV detection and methylation analysis was taken. In a primary analysis, the negative predictive value (NPV) of a GynTect^®-negative test result at V0 for regression was determined. We tested the null hypothesis NPV ≤ 70% against the alternative hypothesis NPV ≥ 90%. Twelve of the eighteen GynTect^®-negative CIN2 patients showed regression (NPV = 67%, 90% CI 44-85%, p = 0.53). Of the 27 GynTect^®-negative CIN3 lesions, 15 regressed (NPV = 56%, 90% CI 38-72%, p = 0.92). Although the majority of GynTect^®-negative lesions regressed, the postulated NPV of ≥90% was not observed. Thus, the clinical relevance for an implementation of the GynTect^® assay for patients undergoing watchful waiting remains questionable. Further studies with longer observation periods should be undertaken.

SUBMITTER: Hoyer H

PROVIDER: S-EPMC10417134 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Evaluation of CIN2/3 Lesion Regression in GynTect<sup>®</sup> DNA Methylation-Marker-Negative Patients in a Longitudinal Study.

Hoyer Heike H Stolte Claudia C Böhmer Gerd G Hampl Monika M Hagemann Ingke I Maier Elisabeth E Denecke Agnieszka A Hirchenhain Christine C Patzke Jan J Jentschke Matthias M Gerick Axel A Heller Tabitha T Hippe Juliane J Wunsch Kristina K Schmitz Martina M Dürst Matthias M

Cancers 20230803 15

Cervical intraepithelial neoplasia (CIN) grade 2/3 has a high spontaneous regression rate, especially among women ≤29 years of age. To reduce overtreatment, reliable prognostic biomarkers would be helpful. The main aim of this study was to analyze the negative predictive value of the methylation marker panel GynTect<sup>®</sup> for lesion regression. In this prospective, multicenter, longitudinal observational proof-of-concept study, women aged ≤29 years with histologically confirmed CIN2 (n = 2 ...[more]

PMID: 37568767

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Project description:IntroductionThe clinical course of high-grade cervical intraepithelial neoplasia (CIN2/3) is characterised by a high spontaneous regression rate. Histological assessment is unable to differentiate between CIN2/3 lesions likely to regress and those likely to persist or progress. Most CIN2/3 lesions are treated by surgical excision, leading to overtreatment of a substantial proportion. In this prospective study, we evaluate the value of DNA methylation of host cell genes, which has shown to be particularly sensitive for the detection of advanced CIN2/3 and cervical cancer, in the prediction of regression or non-regression of CIN2/3 lesions.Methods and analysisThis is a multicentre observational longitudinal study with 24-month follow-up. Women referred for colposcopy with an abnormal cervical scrape, who have been diagnosed with CIN2/3 and a small cervical lesion (≤50% of cervix) will be asked to participate. Participants will be monitored by 6-monthly cytological and colposcopic examination. In case of clinical progression, participants will receive treatment and exit the study protocol. At baseline and during follow-up, self-sampled cervicovaginal brushes and cervical scrapes will be collected for high-risk human papillomavirus (HPV) testing and FAM19A4/miR124-2 methylation analysis. A colposcopy-directed biopsy will be taken from all participants at the last follow-up visit. The primary study endpoint is regression or non-regression at the end of the study based on the histological diagnosis. Regression is defined as CIN1 or less. Non-regression is defined as CIN2 or worse. The secondary study endpoint is defined as HPV clearance (double-negative HPV test at two consecutive time-points). The association between methylation status and regression probability will be evaluated by means of χ2 testing.Ethics and disseminationEthics approval was obtained in all participating clinics. Results of the main study will be submitted for publication in a peer-reviewed journal.Trial registration numberNTR6069; Pre-results.

Project description:IntroductionCervical intraepithelial neoplasia grade 2 (CIN2) represents a spectrum of lesions with variable progression and regression. Pathological diagnosis of CIN2 is subjective and poorly reproducible. Accurate diagnosis and identification of different patterns of CIN2 related to outcome are essential to reduce the risks of overtreatment or undertreatment. It is important to explore novel methods for risk stratification of CIN2 to enable targeted treatment of women at high risk of progression or persistent disease and follow-up of women at low risk. The combination of the novel biomarker human papillomavirus (HPV) E4 with p16INK4a targets steps in the transition from a productive oncogenic HPV infection (CIN1) to a transformed lesion (CIN3) within CIN2. Previous cross-sectional studies suggest that HPV E4 combined with p16INK4a may be valuable for risk assessment of CIN2. However, data on HPV E4/p16INK4a as a predictor for CIN2 regression is lacking.Methods and analysisWe will conduct a historical cohort study including 500 women aged 23-40 years with a first CIN2 diagnosis in Aarhus, Denmark during 2000-2010. Women will be eligible if they have undergone active surveillance and have no previous record of hysterectomy, cone biopsy, and CIN2 or worse. Women will be randomly selected through the Danish Pathology Databank. Tissue samples from women included will be sectioned for p16INK4a and HPV E4 immunohistochemical staining in addition to conventional hematoxylin and eosin (H&E) staining. A positive result will be defined as HPV E4 positive. Through the Danish Pathology Databank, we will collect results on all subsequent cervical biopsies. Regression will be used as the primary outcome.Ethics and disseminationThe study has been approved by the Ethical Committee in Central Denmark Region (1-10-72-60-20) and registered at the Faculty of Health, Aarhus University. Results will be published in a peer-reviewed journal and presented at scientific meetings.Trial registration numberNCT05049252.

Project description:BackgroundScreening for latent tuberculosis infection using Interferon-Gamma Release Assays is a routine procedure prior to the initiation of anti-tumor necrosis factor (TNF) biotherapy or immunosuppressive therapy. However, indeterminate results are relatively frequent and are an obstacle to treatment initiation.AimThe aim of this cross-sectional study was to estimate the frequency of indeterminate QuantiFERON-TB Gold Plus® test results in Tunisian patients, and to analyze the potential clinico-biological risk factors associated with these indeterminate results.MethodsWhole blood samples from 712 patients being monitored for autoimmune diseases and candidates for anti-TNF biotherapy or switch of immunosuppressive therapy were used to screen for latent tuberculosis infection using the QuantiFERON-TB Gold Plus® test. Based on literature background, the following variables were tested for the association with indeterminate results: gender, age, diabetes, immunosuppressive drugs, lymphocyte count, Neutrophil-to-lymphocyte ratio, serum albumin, and estimated glomerular filtration rate.ResultsThe QuantiFERON-TB Gold Plus® test was negative in 572 (80.3%) patients, positive in 106 (14.9%), and indeterminate in 34 (4.8%) cases. Positive results were significantly associated with a family history of confirmed and treated tuberculosis, OR (95% CI) = 52 (20.2-134.3). The use of immunosuppressive drugs and duration of treatment were significantly associated with the occurrence of indeterminate results: OR (95% CI) = 24.5 (5.8-103) and OR (95% CI) = 1.004 (1.002-1.007), respectively. Biologically, lymphopenia, hypoalbuminemia, and decreased estimated glomerular filtration rate were significant risk factors for indeterminate results: p = 5 E-6, p = 4.3 E-4, and p = 0.002, respectively. Thus, a multiple logistic regression model based on these three biological parameters enabled us to develop a predictive score for indeterminate results with a sensitivity of 91.2% and a specificity of 99.9%, AUC = 0.9964 (0.9917-1), p = 2.8 E-52.ConclusionImmunosuppressive therapy, lymphopenia, hypoalbuminemia, and kidney failure appeared to be risk factors for indeterminate QuantiFERON-TB Gold Plus® results.

Dataset Information

Evaluation of CIN2/3 Lesion Regression in GynTect^® DNA Methylation-Marker-Negative Patients in a Longitudinal Study.

Publications

Evaluation of CIN2/3 Lesion Regression in GynTect<sup>®</sup> DNA Methylation-Marker-Negative Patients in a Longitudinal Study.

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Dataset Information

Evaluation of CIN2/3 Lesion Regression in GynTect® DNA Methylation-Marker-Negative Patients in a Longitudinal Study.

Publications

Evaluation of CIN2/3 Lesion Regression in GynTect<sup>®</sup> DNA Methylation-Marker-Negative Patients in a Longitudinal Study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Evaluation of CIN2/3 Lesion Regression in GynTect^® DNA Methylation-Marker-Negative Patients in a Longitudinal Study.