Methylation and Related Anogenital HPV Cancers

肛门癌是同性恋男性面临的一种新的健康危机，尤其是在人类的背景下 免疫缺陷病毒(HIV)感染。与浸润性宫颈癌一样，肛门癌主要是 可归因于慢性、高风险的人类乳头瘤病毒(HPV)感染。这些感染和他们的 相关的低级别和高级别肛门上皮内瘤(AIM)在有以下病史的男性中很常见 容易接受的肛交。尽管肛门发育不良的发生率很高，但恶性肿瘤是一种相对罕见的疾病。 发生了。在国内，对于护理标准和治疗结果没有达成共识 算法在很大程度上并不令人满意。迫切需要确定潜在自然事件中的关键事件 病史，这将使临床医生能够确定哪些人需要立即治疗或 可以一直处于严密的监视之下。更敏感的生物标记物可能会区分男性 从那些没有做到这一点的人身上取得进展，将允许测试更好的临床算法。从长远来看，这些 这些战略将减少发病率和死亡率，并减轻人口的疾病负担。 甲基化是一种适应性的细胞过程，通过使病毒产生来阻碍外来DNA的转录 宿主细胞转录因子和酶较难获得的基因组。我们最近的研究表明 HPV基因组甲基化可能是表观遗传决定因素，负责促进潜伏感染 和临床疾病的进展。本次调查集中在两个目标上，采用流行病学方法和 分子生物学技术。首先，我们将确定之前观察到的 在91名HIV/HPV16混合感染男性中可观察到HPV16基因组甲基化和疾病状态 已经针对AIM进行了评估。第二，利用纵向收集的临床样本，控制 时间依赖协变量的影响，我们将确定特定的甲基化基线模式在 HPV16基因组预测三种高危HPV的甲基化模式。 公共卫生声明：这项研究的结果将通过以下方式改善公众健康 通过识别可靠的生物标志物来提高肛门癌筛查的准确性，最终 防止过早死亡。

Anal cancer is an emerging health crisis for homosexual men, especially within the context of human mmunodeficiency virus (HIV) infection. Like invasive cervical cancer, intra-anal cancers are largely attributable to chronic, high-risk human papillomavirus (HPV) infections. These infections and their associated low- and high-grade anal intraepithelial neoplasias (AIM) are common for men with a history of receptive anal intercourse. Though the prevalence of anal dysplasia is high, malignancy is a relatively rare occurrence. Domestically, there is no consensus for standards of care, and the outcome of treatment algorithms is largely unsatisfactory. There is an urgent need to identify key events in the underlying natural history of disease, which will enable clinicians to determine which individuals need immediate treatment or can remain under careful surveillance. More sensitive biomarkersthat can discriminate between men likely to progress from those that do not will allow better clinical algorithms to be tested. In the long term, these strategies will reduce morbidity and mortality and diminish the population's burden of disease. Methylation is an adaptive cellular process that hinders transcription of foreign DMA by making viral genomes less accessible to host-cell transcription factors and enzymes. Our recent studies suggest methylation of HPV genomes may be an epigenetic determinant, responsible for promoting latent infection and clinical disease progression. This investigation focuses on two aims using epidemiological methods and molecular biology techniques. First, we will determine whether previously observed relationships between methylation of HPV16 genomes and disease state are observable in 91 HIV/HPV16 coinfected men that have been evaluated for AIM. Second, using longitudinally-collected clinical samples and controlling for the effect of time-dependent covariates, we will determine whether particular baseline patterns of methylation in HPV16 genomes predict methylation patterns overtime in three high-risk HPVs. PUBLIC HEALTH STATEMENT: The findings from this study will improve the public's health by improving anal cancer screening accuracy through the identification of reliable biomarkers, to ultimately prevent premature death.