Cancer Risk Stratification of Anal Intraepithelial Neoplasia in Human Immunodeficiency Virus–Positive Men by Validated Methylation Markers Associated With Progression to Cancer

Author:

van der Zee Ramon P123,Richel Olivier4,van Noesel Carel J M5,Ciocănea-Teodorescu Iuliana6,van Splunter Annina P1,ter Braak Timo J1,Nathan Mayura7,Cuming Tamzin7,Sheaff Michael8,Kreuter Alexander9,Meijer Chris J L M1,Quint Wim G V10,de Vries Henry J C311,Prins Jan M2,Steenbergen Renske D M1ORCID

Affiliation:

1. Department of Pathology, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands

2. Department of Internal Medicine, Division of Infectious Diseases, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam Institute for Infection and Immunity (AI&II), Amsterdam, The Netherlands

3. Department of Dermatology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands

4. Department of Internal Medicine, Division of Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands

5. Department of Pathology, Amsterdam University Medical Centers, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands

6. Department of Epidemiology and Biostatistics, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Amsterdam Public Health Research Institute, Amsterdam, The Netherlands

7. Homerton Anal Neoplasia Service, Homerton University Hospital, London, United Kingdom

8. Department of Cellular Pathology, Barts Health National Health Service (NHS) Trust, London, United Kingdom

9. Department of Dermatology, Venerology, and Allergology, Helios St Elisabeth Hospital Oberhausen, University Witten/Herdecke, Oberhausen, Germany

10. DDL Diagnostic Laboratory, Rijswijk, The Netherlands

11. Sexually Transmitted Infections Outpatient Clinic, Department of Infectious Diseases, Public Health Service of Amsterdam (GGD Amsterdam), Amsterdam, The Netherlands

Abstract

Abstract Background High-grade anal intraepithelial neoplasia (HGAIN; AIN2–3) is highly prevalent in HIV+ men, but only a minority of these lesions progress towards cancer. Currently, cancer progression risk cannot be established; therefore, no consensus exists on whether HGAIN should be treated. This study aimed to validate previously identified host cell DNA methylation markers for detection and cancer risk stratification of HGAIN. Methods A large independent cross-sectional series of 345 anal cancer, AIN3, AIN2, AIN1, and normal control biopsies of HIV+ men was tested for DNA methylation of 6 genes using quantitative methylation-specific PCR. We determined accuracy for detection of AIN3 and cancer (AIN3+) by univariable and multivariable logistic regression analysis, followed by leave-one-out cross-validation. Methylation levels were assessed in a series of 10 anal cancer cases with preceding HGAIN at similar anatomic locations, and compared with the cross-sectional series. Results Methylation levels of all genes increased with increasing severity of disease (P < .05). HGAIN revealed a heterogeneous methylation pattern, with a subset resembling cancer. ZNF582 showed highest accuracy (AUC = 0.88) for AIN3+ detection, slightly improved by addition of ASCL1 and SST (AUC = 0.89), forming a marker panel. In the longitudinal series, HGAIN preceding cancer displayed high methylation levels similar to cancers. Conclusions We validated the accuracy of 5 methylation markers for the detection of anal (pre-) cancer. High methylation levels in HGAIN were associated with progression to cancer. These markers provide a promising tool to identify HGAIN in need of treatment, preventing overtreatment of HGAIN with a low cancer progression risk.

Funder

Aidsfonds

KWF Kankerbestrijding

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Microbiology (medical)

Cited by 29 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3