Methylation and Related Anogenital HPV Cancers

肛门癌是一个新兴的健康危机的同性恋男子，特别是在人类的背景下， 免疫缺陷病毒（HIV）感染。与浸润性宫颈癌一样，肛门内癌主要是 可归因于慢性、高风险的人乳头瘤病毒（HPV）感染。这些感染及其 相关的低度和高度肛门上皮内瘤变（AIM）在有以下病史的男性中很常见： 接受性肛交虽然肛门发育不良的患病率很高，但恶性肿瘤相对罕见。 发生。在国内，对治疗标准和治疗结果没有共识 算法在很大程度上不能令人满意。迫切需要查明潜在自然灾害中的关键事件， 病史，这将使临床医生能够确定哪些人需要立即治疗， 可以继续受到严密监视更敏感的生物标志物，可以区分男性， 从那些不允许的进展将允许更好的临床算法被测试。从长远来看，这些 这些战略将降低发病率和死亡率，减轻人口的疾病负担。 甲基化是一种适应性细胞过程，通过使病毒DNA甲基化来阻碍外源DNA的转录。 宿主细胞转录因子和酶不易进入的基因组。我们最近的研究表明 HPV基因组甲基化可能是一种表观遗传决定因素，负责促进潜伏感染 和临床疾病进展。这项调查的重点是两个目标，使用流行病学方法， 分子生物学技术首先，我们将确定之前观察到的之间的关系是否 在91名HIV/HPV 16共感染男性中观察到HPV 16基因组甲基化和疾病状态， 已被评估为AIM。第二，使用临床采集的样本， 时间依赖性协变量的影响，我们将确定是否特定的基线模式的甲基化， HPV 16基因组预测三种高危HPV随时间推移的甲基化模式 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： 通过鉴定可靠的生物标志物来提高肛门癌筛查的准确性， 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.