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: 8630892
• 负责人: Rebecca Bullard-Dillard
• 金额: $ 8.71万
• 依托单位: UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-03-01 至 2016-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8630892
• 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）的头颈部鳞状细胞癌死亡率在全国排名第3 （HNSCC），并超过HNSCC发病率的全国平均水平。此外，非裔美国人（AA）男性 在SC中，HNSCC发病率高于任何其他种族/性别组，死亡率几乎是其他种族/性别组的三倍 在欧洲（EA）男性中观察到的。这种差异与非洲宫颈癌的数据密切相关。 美国（AA）和欧洲美国（EA）妇女在该州。获得保健和早期发现 最有可能在确定AA和EA之间的这些和其他健康差异方面发挥重要作用。 然而，其他因素也可能起作用。高达60%的乳腺癌和25%的HNSCC 例是由于高危人乳头瘤病毒（HR HPV）。HPV阳性癌症似乎是一种独特的 疾病，其特征是整体健康状况明显改善，对治疗的反应更大， 疾病特异性生存率，与HPV阴性癌症相比。初步证据显示， HNSCC中AA患者HPV阳性率远低于EA患者。这一观察结果可能导致 AA男性可能对更具侵袭性的HPV阴性HNSCC特别敏感， 这可能导致这两个群体之间的差距。然而，虽然普遍认为， HPV阳性的HNSCC几乎完全携带HPV 16，这是我们最近在卡罗莱纳的研究中获得的数据。 女性护理研究，调查女性生殖道中HR HPV持续存在的决定因素 大学生们则给出了不同的解释。我们发现HPV类型的分布存在深刻的差异， 导致EA和AA妇女之间持续感染的HPV 16：而HPV 16几乎占所有感染的 在EA妇女中持续感染，它仅占AA妇女中这些感染的%左右。其他HPV 型，如HPV 52和HPV 59在AA中有很好的代表性，但在EA妇女中几乎完全不存在。在 此外，AA女性HR HPV感染的清除率比EA女性慢，相反， HPV感染与细胞学异常的相关性在AA女性中更高。因此，我们 面临着一个矛盾：关于生殖器感染，AA妇女似乎总体上更容易受到HPV介导的 疾病比EA妇女，而AA男性似乎更耐口腔疾病介导 HPV。在对这一明显矛盾的可能解释中，我们选择关注两种可能性， 我们认为这是最合理的 1.除HPV 16外，一种或多种其他HR HPV类型在AA的HNSCC中起重要作用 患者如果是这种情况，那么至少有一个因素导致EA和AA之间的差异， HNSCC可能是其他HR HPV类型。我们将在目标1中直接探讨这种可能性;或 2.尽管HPV的分布不同，但HPV 16是唯一一种容易在人群中繁殖的HR HPV类型 口腔，并仍然是唯一的（或迄今为止最普遍的）类型与HNSCC在这两个 AA和EA患者。如果事实证明是这样，那么AA中HPV阳性癌症的罕见发生率 HPV 16的存在频率约为AA女性的V2，这一事实可以解释男性的发病率 比EA的女人多。性关系仍然主要发生在种族群体内部，而不是跨种族群体， 口交在AA男性和女性中不太常见，并且发病较晚（参见背景和 显著性）。这一发现仍然没有解决为什么HNSCC更频繁， 在AA男性中是致命的，并保证在两个种族中对疾病的分子性质进行调查 组，通过基因表达谱（目的2）。HNSCC可能是AA中的一种不同疾病的想法 患者并不完全牵强，因为有证据表明乳腺癌和前列腺癌也会发展， 在这两个种族群体中表现出不同的方式（见背景和意义）。 假设：零假设是HPV感染的患病率和类型没有差异 AA和EA患者中HNSCC之间的分布。此外，该研究还将测试是否有独特的基因 HPV阳性和HPV阴性癌症的表达谱特征，有助于 揭示了两个种族之间HNSCC发展机制的差异。 沿着这些路线，HPV阳性和HPV阴性HNSCC的初步基因表达研究（其是 作为种子基金的一部分，我们的实验室正在进行这项工作， HNSCC）鉴定了差异表达的基因，这些基因可能在决定不同的致病性中起作用。 以及这些肿瘤的临床特征。