Pauciullo Silvia, Colombo Daniele, Zulian Verdiana, Sciamanna Roberta, Coppola Antonio, Scarabello Alessandra, Del Nonno Franca, Garbuglia Anna Rosa
Laboratory of Virology, National Institute for Infectious Diseases "Lazzaro Spallanzani" (IRCCS), 00149 Rome, Italy.
Pathology Unit, National Institute for Infectious Diseases "Lazzaro Spallanzani" (IRCCS), 00149 Rome, Italy.
Biomedicines. 2024 Aug 13;12(8):1838. doi: 10.3390/biomedicines12081838.
Human papillomavirus (HPV) infection is linked to several cancers, including anal and oral cancers. The incidence of anal cancer is particularly high among HIV-positive men who have sex with men (MSM). DNA methylation markers have shown promise as biomarkers for identifying precancerous lesions and cancer in HPV-infected individuals. The aim of this study was to investigate the correlation of DNA methylation with HPV infection in oral samples and the correlation of DNA methylation with lesion degree in the anal samples of HIV-positive MSM.
This study investigated DNA methylation in oral and anal samples from HIV-positive MSM at the National Institute for Infectious Diseases (INMI) in Rome, Italy. Exfoliated oral epithelial cells and anal samples were collected and analyzed for 28 HPV genotypes using the Allplex 28 HPV assay. DNA methylation was assessed with the PrecursorM+ kit for oral samples and the AnoGyn kit for anal samples, focusing on the promoter regions of specific genes.
The study included 63 participants, with a median age of 49 and a median CD4+ count of 705 cells/µL. The oral samples showed HPV16 as the most common type, with 22% testing positive for DNA methylation. The anal samples exhibited HPV-related methylation changes linked to cytological lesions, with a 30% increase in the observed ddCt ratio. Significant differences were found in both ASCL1 and ZNF582 genes, particularly for HSILNILM and HSILLSIL lesions. Of the samples with an increased ddCt ratio, 80% were from patients over 35 years old, and multiple HPV infections were common.
DNA methylation markers could be valuable in identifying high-risk HPV infections in oral samples and detecting potential precancerous lesions in anal samples. These markers may enhance the early detection and prevention strategies for HPV-related cancers in high-risk populations, with follow-up data indicating potential for monitoring lesion progression.
人乳头瘤病毒（HPV）感染与多种癌症相关，包括肛门癌和口腔癌。在与男性发生性关系的HIV阳性男性（男男性行为者）中，肛门癌的发病率尤其高。DNA甲基化标记物已显示出作为识别HPV感染个体癌前病变和癌症生物标志物的潜力。本研究的目的是调查口腔样本中DNA甲基化与HPV感染的相关性，以及HIV阳性男男性行为者肛门样本中DNA甲基化与病变程度的相关性。
本研究在意大利罗马的国家传染病研究所（INMI）对HIV阳性男男性行为者的口腔和肛门样本中的DNA甲基化进行了调查。收集脱落的口腔上皮细胞和肛门样本，并使用Allplex 28 HPV检测法分析28种HPV基因型。使用PrecursorM+试剂盒检测口腔样本的DNA甲基化，使用AnoGyn试剂盒检测肛门样本的DNA甲基化，重点关注特定基因的启动子区域。
该研究纳入了63名参与者，中位年龄为49岁，CD4+细胞计数中位数为705个/微升。口腔样本中HPV16是最常见的类型，22%的样本DNA甲基化检测呈阳性。肛门样本显示出与细胞学病变相关的HPV相关甲基化变化，观察到的数据下降临界值（ddCt）比值增加了30%。在ASCL1和ZNF582基因中均发现了显著差异，特别是对于高级别鳞状上皮内病变（HSIL）/低级别鳞状上皮内病变（LSIL）和HSIL/HSIL病变。在ddCt比值增加的样本中，80%来自35岁以上的患者，多重HPV感染很常见。
DNA甲基化标记物在识别口腔样本中的高危HPV感染和检测肛门样本中的潜在癌前病变方面可能具有重要价值。这些标记物可能会加强高危人群中HPV相关癌症的早期检测和预防策略，后续数据表明其具有监测病变进展的潜力。
