Role of HPV in Head and Neck Cancer in African Am & European Am Patients

HPV 在非洲美洲头颈癌中的作用

• 批准号: 8580137
• 负责人: Rebecca Bullard-Dillard
• 金额: $ 10.07万
• 依托单位: UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-03-04 至 2015-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8580137
• 关键词: Accounting; African; African American; Alcohol consumption; American; Biological Assay; Biological Markers; Caring; Characteristics; Clinical; Clinical Data; DNA; Data; Data Analyses; Development; Disease; Early Diagnosis; Epidermal Growth Factor Receptor; European; Female; Frequencies; Frozen Sections; Gender; Gene Expression; Gene Expression Profiling; Genes; Genital system; Grant; HPV-High Risk; Head and Neck Cancer; Head and Neck Squamous Cell Carcinoma; Health Services Accessibility; Health Status; Hepatocyte Growth Factor; Human; Human Papillomavirus; Human papilloma virus infection; Human papillomavirus 16; Incidence; Infection; Investigation; Label; Laboratories; Lead; Left; Light; Link; MET Oncogene; Malignant Neoplasms; Malignant neoplasm of cervix uteri; Malignant neoplasm of prostate; Mediating; Medical; Metabolic Clearance Rate; Molecular; Molecular Profiling; Mouth Diseases; Nature; Oncogenes; Oral Sex; Oral cavity; Oropharyngeal; Patients; Play; Prevalence; Proteins; Protocols documentation; RNA; Race; Recurrence; Research; Resistance; Risk Factors; Role; Sampling; Seeds; Site; Sleep Apnea Syndromes; Smoking; South Carolina; Specimen; Staging; Testing; Time; Tissue Banking; Tissue Banks; Tonsil; Universities; Woman; base; cohort; cyanine dye 5; genital infection; health disparity; health equity; male; malignant breast neoplasm; men; mortality; receptor; response; social; tumor; university student

South Carolina (SC) ranks 3^" in the nation in mortality rates for head and neck squamous cell carcinoma (HNSCC), and exceeds national averages for incidence of HNSCC. In addition, African American (AA) males in SC have a higher incidence of HNSCC than any other racial/gender group, and a mortality rate almost threefold that observed in European (EA) males. This disparity closely parallels data for cervical cancer in African American (AA) and European American (EA) women in the state. Access to health care and early detection most likely play an important role in determining these and other health disparities between AA and EA. However, additional factors may also contribute. Up to 60% of oropharynegeal cancers and 25% of all HNSCC cases are due to high-risk human papillomaviruses (HR HPV). HPV-positive cancers appear to be a distinct disease, characterized by significantly better overall health status, greater response to therapy, and better disease-specific survival, in comparison with HPV-negative cancers. Preliminary evidence indicates that the prevalence of HPV positivity in HNSCC is much lower in AA than in EA patients. This observation may lead to the conclusion that AA men may be particularly susceptible to the more aggressive HPV-negative HNSCC, and this may contribute to the disparity between these two groups. However, while it is generally accepted that HPV positive HNSCC harbor almost exclusively HPV16, data recently obtained in the course of our Carolina Women's Care Study, which investigates the determinants of HR HPV persistence in the genital tract of female college students, point to a different explanation. We find profound differences in the distribution of HPV types that cause persistent infection between EA and AA women: while HPV16 accounts for almost V^ of all persistent infections in EA women, it accounts only for about % of these infections in AA women. Other HPV types, such as HPV52 and HPV59 are well represented in AA, but almost entirely absent in EA women. In addition, the rate of clearance of HR HPV infection is slower in AA than in EA women and, conversely, the rate at which HPV infection is associated with cytological abnormalities is higher in AA women. Hence, we are confronted with a paradox: with regard to genital infections, AA women seem overall more susceptible to HPVmediated disease than EA women, while AA men appear to be more resistant to oral disease mediated by HPV. Among the possible explanations for this apparent paradox, we elected to focus on two possibilities, which we believe are most plausible: 1. One or more additional HR HPV types, other than HPV16, play a significant role in HNSCC of AA patients. If this is the case, then at least one contributing factor to the disparity between EA and AA in HNSCC would be other HR HPV types. We will directly explore this possibility in Aim 1; or 2. Despite the different distribution of HPVs, HPV16 is the only HR HPV type that easily thrives in the oral cavity, and remains the only (or by far the most prevalent) type associated with HNSCC in both AA and EA patients. If this turns out to be the case, the rare occurrence of HPVpositive cancers in AA men may be explained based on the fact that HPV16 is present with about V2 the frequency in AA women than in EA women. Sexual relations still occur predominantly within, rather than across racial groups, and oral sex is less common and has a later onset among AA men and women (see Background and Significance). This finding would still leave open the question as to why HNSCC is more frequent and more deadly in AA men, and warrant an investigation of the molecular nature of the disease in both racial groups, by gene expression profiling (Aim 2). The idea that HNSCC may be a different disease in AA patients is not totally far-fetched, as there is evidence that breast and prostate cancer also develop and behave in distinct ways in the two racial groups (see Background and Significance). Hypothesis: the null hypothesis is that there are no differences in prevalence of HPV infection and type distribution between HNSCC in AA and EA patients. In addition, the study will test whether distinctive gene expression profiles characterize HPV positive and HPV negative cancers between racial groups, helping to shed light on differences in the mechanisms of HNSCC development between the two races. Along these lines, preliminary gene expression studies of HPVpositive and HPVnegative HNSCC (which are ongoing in our laboratory as a part of a seed grant leading to this and other collaborative proposals on HNSCC) identified differentially-expressed genes that may play a role in determining the different pathogenetic and clinical characteristics of these tumors.

南卡罗来纳州（SC）的死亡率为3^“头颈部鳞状细胞癌的死亡率为3” （HNSCC），并且超过了HNSCC发病率的全国平均值。此外，非裔美国人（AA）男性 在SC中，HNSCC的发病率高于任何其他种族/性别组，死亡率几乎三倍 在欧洲（EA）男性中观察到的。这种差异与非洲宫颈癌的数据紧密相似 该州的美国（AA）和欧美（EA）妇女。获得医疗保健和早期检测 在确定AA和EA之间的这些健康差异方面，最有可能发挥重要作用。 但是，其他因素也可能会造成贡献。多达60％的口咽癌和所有HNSCC的25％ 病例是由于高风险的人乳头瘤病毒（HR HPV）。 HPV阳性癌症似乎是独特的 疾病的特征是总体健康状况明显更好，对治疗的反应更大，并且更好 与HPV阴性癌症相比，疾病特异性的生存期。初步证据表明 AA中HNSCC中HPV阳性的患病率比EA患者低得多。这个观察可能会导致 AA男子可能特别容易受到更具侵略性的HPV阴性HNSCC的结论，以及 这可能导致这两组之间的差异。但是，尽管普遍认为 HPV阳性HNSCC港口几乎完全是HPV16，最近在我们卡罗来纳州获得的数据 妇女护理研究，研究女性生殖道中HR HPV持久性的决定因素 大学生，指出不同的解释。我们发现HPV类型的分布有很大的差异 这会导致EA和AA妇女之间的持续感染：而HPV16几乎占所有人的v^ EA妇女的持续感染，它仅占AA女性这些感染的百分比。其他HPV 诸如HPV52和HPV59之类的类型在AA中很好地代表，但在EA女性中几乎完全不存在。在 此外，AA中HR HPV感染的清除率比EA女性慢，相反 在AA女性中，HPV感染与细胞学异常相关的相关性更高。因此，我们是 面对悖论：关于生殖器感染，AA妇女总体似乎更容易受到HPVSIDED的影响 疾病比EA女性，而AA男性似乎对介导的口腔疾病更具抵抗力 HPV。在对这种明显悖论的可能解释中，我们选择着重于两种可能性， 我们认为这是最合理的： 1。一种或多种HR HPV类型（HPV16）在AA的HNSCC中起重要作用 患者。如果是这种情况，那么至少有一个导致EA与AA之间差异的因素 HNSCC将是其他HR HPV类型。我们将在AIM 1中直接探索这种可能性；或者 2。尽管HPV的分布不同，但HPV16是唯一轻松繁衍生息的HR HPV类型 口腔，仍然是与HNSCC相关的唯一（或迄今为止最普遍的）类型 AA和EA患者。如果事实证明是这种情况，那么AA中HPVPOSITER CANCER的罕见出现 可能会根据HPV16存在大约v2的频率来解释男性 比在EA女性中。性关系仍然主要发生在内部，而不是在种族群体中， 口交不那么普遍，在AA男性和女人中发病以后（请参阅背景和 意义）。这一发现仍然会使HNSCC为何更频繁，更多，更多 在AA男子中致命，并保证对这两种种族中疾病的分子性质进行调查 组，通过基因表达分析（AIM 2）。 HNSCC在AA中可能是另一种疾病的想法 患者并没有完全牵强，因为有证据表明乳腺癌和前列腺癌也会发展为 在两个种族群体中以不同的方式行事（请参阅背景和意义）。 假设：零假设是HPV感染和类型的患病率没有差异 AA和EA患者中HNSCC之间的分布。此外，该研究将测试是否独特的基因 表达曲线表征了种族群体之间HPV阳性和HPV负癌的特征，有助于 阐明了两个种族之间HNSCC发展机制的差异。 沿着这些线，HPVPostistil和hpvnegate HNSCC的初步基因表达研究（这是 作为种子赠款的一部分，我们的实验室正在进行，导致了有关此和其他合作提议 HNSCC）鉴定出差异表达的基因，这些基因可能在确定不同的致病性方面发挥作用 和这些肿瘤的临床特征。