Background: Methylation of viral DNA has been proposed as a novel biomarker for triage of human papillomavirus (HPV) positive women at screening. This systematic review and meta-analysis aims to assess how methylation levels change with disease severity and to determine diagnostic test accuracy (DTA) in detecting high-grade cervical intra-epithelial neoplasia (CIN).
Methods: We performed searches in MEDLINE, EMBASE and CENTRAL from inception to October 2019. Studies were eligible if they explored HPV methylation levels in HPV positive women. Data were extracted in duplicate and requested from authors where necessary. Random-effects models and a bivariate mixed-effects binary regression model were applied to determine pooled effect estimates.
Findings: 44 studies with 8819 high-risk HPV positive women were eligible. The pooled estimates for positive methylation rate in HPV16 L1 gene were higher for high-grade CIN (≥CIN2/high-grade squamous intra-epithelial lesion (HSIL) (95% confidence interval (95%CI:72·7% (47·8-92·2))) vs. low-grade CIN (≤CIN1/low-grade squamous intra-epithelial lesion (LSIL) (44·4% (95%CI:16·0-74·1))). Pooled difference in mean methylation level was significantly higher in ≥CIN2/HSIL vs. ≤CIN1/LSIL for HPV16 L1 (11·3% (95%CI:6·5-16·1)). Pooled odds ratio of HPV16 L1 methylation was 5·5 (95%CI:3·5-8·5) for ≥CIN2/HSIL vs. ≤CIN1/LSIL (p < 0·0001). HPV16 L1/L2 genes performed best in predicting CIN2 or worse (pooled sensitivity 77% (95%CI:63-87), specificity 64% (95%CI:55-71), area under the curve (0·73 (95%CI:0·69-0·77)).
Interpretation: Higher HPV methylation is associated with increased disease severity, whilst HPV16 L1/L2 genes demonstrated high diagnostic accuracy to detect high-grade CIN in HPV16 positive women. Direct clinical use is limited by the need for a multi-genotype and standardised assays. Next-generation multiplex HPV sequencing assays are under development and allow potential for rapid, automated and low-cost methylation testing.
Funding: NIHR, Genesis Research Trust, Imperial Healthcare Charity, Wellcome Trust NIHR Imperial BRC, European Union's Horizon 2020.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6921230 | PMC |
| http://dx.doi.org/10.1016/j.ebiom.2019.10.053 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Educational Interventions to Improve Knowledge and Attitudes Toward Human Papillomavirus (HPV) Vaccination and Cervical Cancer Screening Among Japanese University Students.
Cureus
December 2024
Department of Obstetrics and Gynecology, Osaka Metropolitan University Graduate School of Medicine, Osaka, JPN.
Aim This study evaluates university students' knowledge and attitudes toward Human Papillomavirus (HPV) vaccination and cervical cancer screening and assesses the impact of educational interventions. Methods Participants from Osaka Metropolitan University, Osaka City University, and Osaka Prefecture University completed questionnaires before and after receiving educational materials, including cartoons and a video featuring medical professionals. We compared the correct answer rates for knowledge-related questions and evaluated changes in behavioral characteristics and attitudes toward HPV vaccination and cervical cancer screening before and after distributing the educational materials.
View Article and Find Full Text PDFEffect of information awareness on attitudes toward human papillomavirus vaccination intentions in Japan.
Vaccine X
January 2025
Minpapi Association, Tokyo, Japan.
Background: The Human Papillomavirus (HPV) vaccination rate among Japanese high school girls remains critically low, reflecting ongoing public apprehension and misinformation. This study explores the relationship between information presentation and attitudes toward HPV vaccination in Japan.
Methods: We conducted a web-based survey of female high school students aged 15 to 16 and mothers of daughters of similar age across Japan.
Head and Neck Squamous Cell Carcinoma of Unknown Primary-Who Can Be Offered Surgery as the Sole Treatment Modality? A Systematic Review.
Clin Otolaryngol
January 2025
Consultant ENT/Head and Neck Surgeon, Department of Otolaryngology/Head and Neck Surgery, University Hospitals Dorset NHS Foundation Trust. Professor of Head and Neck Surgical Oncology, University of Southampton, United Kingdom.
Objective: Evaluate the role of surgery as the sole treatment modality for patients with cervical head and neck squamous cell carcinoma of unknown primary (HNSCCUP).
Design: Systematic review of observational cohort studies with qualitative synthesis.
Setting: PubMed, Ovid EMBASE, and Cochrane Controlled register of Trials (CENTRAL) were screened from January 2000 up to October 2021.
Non-colorectal Cancer Screening and Vaccinations in Patients with Inflammatory Bowel Disease: Expert Review.
Clin Gastroenterol Hepatol
January 2025
Inflammatory Bowel Disease Center, Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville FL. Electronic address:
Description: The aim of this American Gastroenterological Association (AGA) Clinical Practice Update (CPU) is to provide best practice advice (BPA) statements for gastroenterologists and other health care providers who provide care to patients with inflammatory bowel disease (IBD). The focus is on IBD-specific screenings (excluding colorectal cancer screening, which is discussed separately) and vaccinations. We provide guidance to ensure that patients are up to date with the disease-specific cancer screenings, vaccinations, as well as advice for mental health and general wellbeing.
View Article and Find Full Text PDFDeep learning for predicting prognostic consensus molecular subtypes in cervical cancer from histology images.
NPJ Precis Oncol
January 2025
Tissue Image Analytics Centre, Department of Computer Science, University of Warwick, Coventry, United Kingdom.
Article Synopsis
- Cervical cancer is the fourth most common cancer in women globally, and this study introduces a deep learning framework to predict molecular subtypes in HPV-positive cervical squamous cell carcinoma using histology slides.
- The research analyzed three cohorts with 545 patients, demonstrating that the Digital-CMS scores can effectively predict both disease-specific and disease-free survival outcomes.
- Furthermore, the study found significant differences in the tumor microenvironment between subtypes, highlighting potential biomarkers and therapeutic targets that could guide clinical applications for better patient management.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!