Jary Aude, van der Zee Ramon P, Jongen Vita, Ter Braak Timo J, Kim Yongsoo, Meijer Chris J L M, van Noesel Carel J M, de Vries Henry J C, van der Loeff Maarten F Schim, Steenbergen Renske D M
Pathology, Amsterdam UMC Location VU University, Amsterdam, The Netherlands.
Cancer Center Amsterdam, Imaging and Biomarkers, Amsterdam, The Netherlands.
J Med Virol. 2025 May;97(5):e70397. doi: 10.1002/jmv.70397.
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.
肛管鳞状细胞癌通常与人乳头瘤病毒（HPV）感染相关，并由低级别和高级别肛管病变（低级别鳞状上皮内病变；高级别鳞状上皮内病变）发展而来。我们对以纵向方式收集的配对低级别和高级别肛管病变进行了分子比较，以评估它们之间的关系。对22名男性的50份活检样本进行了全面的分子分析，这些男性在基线时（T0）被诊断为低级别鳞状上皮内病变，在随访期间（T1）发展为高级别鳞状上皮内病变：HPV分型和HPV16变体、细胞DNA甲基化水平以及拷贝数变异（CNA）。经过组织病理学复查，23份活检样本被分类为低级别鳞状上皮内病变，27份被分类为高级别鳞状上皮内病变。与低级别鳞状上皮内病变相比，高级别鳞状上皮内病变的甲基化水平和CNA均显著增加。在22名患者中的15名中，T0时的低级别鳞状上皮内病变与T1时的高级别鳞状上皮内病变相关。其中，6名患者在随访时高级别鳞状上皮内病变中显示HPV型别持续存在，甲基化水平和CNA相似或增加。6名患者在随访活检中携带不同的HPV型别，而在3名患者中，一个或两个病变中未检测到HPV或无法分型。一部分由低级别鳞状上皮内病变发展而来的高级别鳞状上皮内病变显示HPV型别持续存在且分子改变增加，这表明一些低级别鳞状上皮内病变可能进展为高级别鳞状上皮内病变。相比之下，另一部分由低级别鳞状上皮内病变发展而来的高级别鳞状上皮内病变中的HPV型别转换，可能提示肛管癌发生的另一种途径，即高级别鳞状上皮内病变直接发生。
