Molecular Insights Into the Natural History of Anal HSIL

IF 6.8 3区医学 Q1 VIROLOGY

Journal of Medical Virology Pub Date : 2025-05-21 DOI:10.1002/jmv.70397

Aude Jary, Ramon P. van der Zee, Vita Jongen, Timo J. Ter Braak, Yongsoo Kim, Chris J. L. M. Meijer, Carel J. M. van Noesel, Henry J. C. de Vries, Maarten F. Schim van der Loeff, Renske D. M. Steenbergen

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Abstract

Anal squamous cell carcinoma is commonly associated with human papillomavirus (HPV) infection and preceded by low- and high-grade anal lesions (LSIL; HSIL). We performed a molecular comparison on paired LSIL- and HSIL-lesions collected in a longitudinal fashion to assess their relationship. Fifty biopsies from 22 men diagnosed with LSIL at baseline (T0) who developed HSIL during follow-up (T1) were subjected to a comprehensive molecular analysis: HPV-typing and HPV16 variant, cellular DNA methylation levels, and copy number aberrations (CNA). After histopathological revision, 23 biopsies were classified as LSIL and 27 as HSIL. Both methylation levels and CNA were significantly increased in HSIL compared to LSIL. In 15 out of 22 patients, LSIL at T0 was associated with HSIL at T1. Among them, six showed HPV-type persistence with similar or increased methylation levels and CNA in the HSIL at follow-up. Six patients harbored a different HPV-type in the follow-up biopsy, while in three patients, HPV was not detected or not-typable in one or both lesions. A subset of HSIL preceded by LSIL displayed both HPV-type persistence and an increase in molecular alterations, suggesting that some LSIL may progress to HSIL. In contrast, the HPV-type switch in another subset of HSIL preceded by LSIL, may suggest an alternative pathway of anal carcinogenesis, where HSIL develop directly.

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肛门HSIL自然史的分子研究

肛门鳞状细胞癌通常与人乳头瘤病毒（HPV）感染相关，并伴有低级别和高级别肛门病变(LSIL；HSIL)。我们对以纵向方式收集的配对LSIL和hsil病变进行了分子比较，以评估它们的关系。来自22名基线（T0）诊断为LSIL的男性(随访（T1）期间发展为HSIL的50例活检进行了全面的分子分析：hpv分型和HPV16变异，细胞DNA甲基化水平和拷贝数畸变（CNA）。经组织病理学复查，23例活检为低级别鳞状上皮性病变，27例为高级别鳞状上皮性病变。与LSIL相比，HSIL的甲基化水平和CNA均显著升高。22例患者中有15例，T0时的LSIL与T1时的HSIL相关。其中6例显示hpv型持续性，随访时HSIL的甲基化水平和CNA水平相似或增加。6例患者在随访活检中携带不同的HPV类型，而3例患者在一个或两个病变中未检测到HPV或无法分型。在LSIL之前的HSIL的一个子集显示hpv型持久性和分子改变的增加，这表明一些LSIL可能进展为HSIL。相比之下，在另一种HSIL亚群中，在LSIL之前的hpv型转换可能提示肛门癌变的另一种途径，其中HSIL直接发展。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Medical Virology 医学-病毒学

CiteScore

23.20

自引率

2.40%

发文量

777

审稿时长

1 months

期刊介绍： The Journal of Medical Virology focuses on publishing original scientific papers on both basic and applied research related to viruses that affect humans. The journal publishes reports covering a wide range of topics, including the characterization, diagnosis, epidemiology, immunology, and pathogenesis of human virus infections. It also includes studies on virus morphology, genetics, replication, and interactions with host cells. The intended readership of the journal includes virologists, microbiologists, immunologists, infectious disease specialists, diagnostic laboratory technologists, epidemiologists, hematologists, and cell biologists. The Journal of Medical Virology is indexed and abstracted in various databases, including Abstracts in Anthropology (Sage), CABI, AgBiotech News & Information, National Agricultural Library, Biological Abstracts, Embase, Global Health, Web of Science, Veterinary Bulletin, and others.