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A systematic review and meta-analysis evaluated DNA methylation changes across pre-cancerous anal intraepithelial neoplasia (AIN-1, -2, -3) and cancerous squamous cell carcinoma (SCC) lesions. PubMed, Scopus, and Web of Science searches were conducted under PRISMA 2020, quality assessed with QUADAS-2, and diagnostic accuracy summarized using pooled sensitivity, specificity, prevalence, and DOR. Eight studies (1555 samples) showed higher methylation prevalence in more severe grades, with AUC for ≥AIN2 of 0.68 (95% CI 0.63–0.73). Findings support clinical triage and monitoring, while standardized protocols and prospective validation are required.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/diagnostic-performance-of-host-and-viral-dna-methylation-analysis-in-the-identification-of-anal-intraepithelial-neoplasia-and-cancer-systematic-review-and-meta-analysis/329119/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/diagnostic-performance-of-host-and-viral-dna-methylation-analysis-in-the-identification-of-anal-intraepithelial-neoplasia-and-cancer-systematic-review-and-meta-analysis/329119.png","ImageObject",300,407,{"name":92,"@type":93},"River Wang","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-27","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":44},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What question does the review address about DNA methylation biomarkers?","Question",{"text":112,"@type":113},"It evaluates how DNA methylation levels change in anal intraepithelial neoplasia (AIN grades) and anal squamous cell carcinoma (SCC), and how well methylation-based testing can detect high-grade lesions.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How were included studies selected and quality assessed?",{"text":117,"@type":113},"Searches were performed in PubMed, Scopus, and Web of Science following PRISMA 2020, observational studies were included based on reported methylation levels by lesion grade and target genes, and study quality was assessed with QUADAS-2.",{"name":119,"@type":110,"acceptedAnswer":120},"What diagnostic performance was reported for detecting high-grade lesions (≥AIN2)?",{"text":121,"@type":113},"The pooled area under the curve (AUC) for diagnosis of ≥AIN2 was 0.68 (95% CI 0.63–0.73), with higher diagnostic odds ratios observed for more severe lesions.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},329119,1790313556,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":44,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145,"preview_page_count":4},1099514067438,"https://ap-avatar.wpscdn.com/avatar/100002539ee87300030?x-image-process=image/resize,m_fixed,w_180,h_180&k=1780474512215547542","healthcare  \nSystematic Review  \nDiagnostic Performance of Host and Viral DNA Methylation Analysis in the Identification of Anal Intraepithelial Neoplasia and Cancer: Systematic Review and Meta-Analysis  \nNarcisa Muresu 1, *, Mariangela Valentina Puci 2, Giovanni Sotgiu 2, Illari Sechi 3, Andrea Cossu 3, Manuela Usai 4 and Andrea Fausto Piana 3  \nCitation: Muresu, N.; Puci, M.V.; Sotgiu, G.; Sechi, I.; Cossu, A.;  \nUsai, M.; Piana, A.F. Diagnostic Performance of Host and Viral DNA Methylation Analysis in the Identification of Anal Intraepithelial Neoplasia and Cancer: Systematic Review and Meta-Analysis. Healthcare 2024, 12, 1951. [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.3390/healthcare12191951](10.3390/healthcare12191951)  \nAcademic Editor: Kavita Batra  \nReceived: 13 August 2024  \nRevised: 17 September 2024  \nAccepted: 27 September 2024  \nPublished: 30 September 2024  \nCopyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Medical Management, Hygiene, Epidemiology and Hospital Infection, University Hospital of Sassari, 07100 Sassari, Italy  \n2 Clinical Epidemiology and Medical Statistics Unit, Department of Medicine, Surgery and Pharmacy, University of Sassari, 07100 Sassari, Italy; mvpuci@uniss.it (M.V.P.); gsotgiu@uniss.it (G.S.)  \n3 Department of Medicine, Surgery and Pharmacy, University of Sassari, 07100 Sassari, Italy;  \n[illasechi@uniss.it](illasechi@uniss.it) (I.S.); [andreacossu@uniss.it](andreacossu@uniss.it) (A.C.); [piana@uniss.it](piana@uniss.it) (A.F.P.)  \n4 Department of Humanities and Social Science, University of Sassari, 07100 Sassari, Italy; [manuelausai@hotmail.com](manuelausai@hotmail.com)  \n* [Correspondence: nmuresu@uniss.it](Correspondence: nmuresu@uniss.it)  \nAbstract: Introduction: DNA methylation-based biomarkers have been investigated as useful tools in the carcinogenesis process, including the triage of HPV-associated cancers. In this context, we conducted a systematic review and meta-analysis focused on evaluating the changes in the level of DNA methylation in cases of pre-cancerous (i.e., anal intraepithelial neoplasia, AIN-1, -2., -3) and cancerous (i.e., squamous cell carcinoma, SCC) anal lesions. Methods: A research in the PubMed, Scopus, and Web of Science databases was carried out, following the PRISMA 2020 protocol, using the following keywords: “anal cancer”,“anal intraepithelial neoplasia”,“methylation”, and “epigenetic”. All observational studies that reported the level of DNA methylation by grade of anal lesions and for different target genes were included. The QUADAS-2 tool was used to assess the studies’ quality, whereas pooled prevalence, sensitivity, specificity, and diagnostic odds ratio (DOR) were employed to verify the accuracy of the test in the detection of high-grade lesions. Results: Eight studies met the inclusion criteria, involving a total of 1555 clinical samples. The prevalence of methylationpositive samples by histological grading was 27%, 45%, 54%, and 98% for AIN1, AIN2, AIN3, and SCC, respectively. Similar results were observed for the DOR, with higher ORs in more severe lesions. The pooled AUC (95%CI) for the diagnosis of ≥AIN2 was 0.68 (0.63–0.73) . Conclusions: The present review and meta-analysis support the introduction of DNA methylation-based biomarkers in the triage of subjects with low-grade anal lesions and in the monitoring of treatment outcomes. Standardized protocols and a prospective study design are needed to implement methylation tests in clinical practice.  \nKeywords: HPV; anal cancer; DNA methylation test; biomarkers; epigenetic  \n1. Introduction  \nThe overall incidence and mortality of anal cancer in 2022 accounted for more t","cbCaifhwnOs7vxji","https://ap.wps.com/l/cbCaifhwnOs7vxji","pdf",2872172,13,"English","# Introduction\n# Methods\n# Results\n# Conclusions","[{\"question\":\"What question does the review address about DNA methylation biomarkers?\",\"answer\":\"It evaluates how DNA methylation levels change in anal intraepithelial neoplasia (AIN grades) and anal squamous cell carcinoma (SCC), and how well methylation-based testing can detect high-grade lesions.\"},{\"question\":\"How were included studies selected and quality assessed?\",\"answer\":\"Searches were performed in PubMed, Scopus, and Web of Science following PRISMA 2020, observational studies were included based on reported methylation levels by lesion grade and target genes, and study quality was assessed with QUADAS-2.\"},{\"question\":\"What diagnostic performance was reported for detecting high-grade lesions (≥AIN2)?\",\"answer\":\"The pooled area under the curve (AUC) for diagnosis of ≥AIN2 was 0.68 (95% CI 0.63–0.73), with higher diagnostic odds ratios observed for more severe lesions.\"}]","Diagnostic Performance of Host and Viral DNA Methylation Analysis in the Identification of Anal Intraepithelial Neoplasia and Cancer - Systematic Review and Meta-Analysis | PDF",1789982607,33]