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

南卡罗来纳州(南卡罗来纳州)头颈部鳞状细胞癌死亡率在全国排名3^“ (HNSCC)，并超过HNSCC的全国平均发病率。此外，非洲裔美国人(AA)男性 在SC中，HNSCC的发病率比任何其他种族/性别群体都要高，死亡率几乎是其他种族/性别的三倍 在欧洲(EA)男性身上观察到了这一点。这一差异与非洲宫颈癌的数据非常相似。 美国(AA)和欧洲美国(EA)妇女在该州。获得保健和及早发现 在确定AA和EA之间的这些和其他健康差异方面，最有可能发挥重要作用。 然而，其他因素也可能起到作用。高达60%的口咽癌和25%的HNSCC 病例是由高危人类乳头瘤病毒(HR HPV)引起的。HPV阳性的癌症似乎是一种截然不同的 疾病，其特征是总体健康状况显著改善，对治疗的反应更好， 与HPV阴性癌症相比，疾病特有的存活率。初步证据表明， 再障患者HNSCC中HPV阳性率明显低于EA患者。这一观察结果可能会导致 结论是AA男性可能特别容易患上更具侵袭性的HPV阴性HNSCC，以及 这可能导致了这两个群体之间的差距。然而，尽管人们普遍认为 HPV阳性的HNSCC几乎完全是HPV16，最近在我们的卡罗莱纳病程中获得的数据 妇女关怀研究--调查HPV在女性生殖道中持续存在的决定因素 大学生们则指出了不同的解释。我们发现人类乳头状瘤病毒类型的分布存在着深刻的差异 导致EA和AA女性持续感染的原因：而HPV16几乎占所有感染的V^ 在EA女性中持续感染，它只占AA女性这些感染的大约%。其他人乳头瘤病毒 HPV52和HPV59等类型在再生障碍性贫血中有很好的代表性，但在EA女性中几乎完全缺失。在……里面 此外，再生障碍性贫血患者HR HPV感染的清除速度慢于EA女性，相反， 在AA妇女中，HPV感染与细胞学异常相关的比例更高。因此，我们是 面对一个悖论：关于生殖器感染，再生障碍性贫血女性总体上似乎更容易感染HPV媒介 与EA女性相比，AA男性似乎更能抵抗由 人类乳头瘤病毒。在对这一明显悖论的可能解释中，我们选择专注于两种可能性， 我们认为这是最有道理的： 1.在AA的HNSCC中，除HPV16外，另有一种或多种HR HPV类型起重要作用 病人。如果是这样的话，至少有一个因素导致了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中直接探讨这一可能性；或 2.尽管HPV的分布不同，但HPV16是唯一一种容易在 口腔，并且仍然是唯一(或迄今为止最常见的)与HNSCC相关的类型 AA和EA患者。如果事实证明是这样的话，再生障碍性贫血中罕见的HPV阳性癌症 男性的解释可能基于这样一个事实，即HPV16存在的频率约为V2，而AA女性的频率约为V2 而不是电针女性。性关系仍然主要发生在种族群体内部，而不是跨种族群体，以及 口交不太常见，在再障男性和女性中起病较晚(见背景和 意义)。这一发现仍然留下了一个悬而未决的问题，为什么HNSCC更频繁、更 在AA男性中是致命的，并需要对这两个种族的疾病的分子性质进行调查 分组，通过基因表达谱(目标2)。认为HNSCC可能是再生障碍性贫血的另一种疾病的想法 患者并不完全是牵强的，因为有证据表明乳腺癌和前列腺癌也会发展和 在两个种族群体中表现出不同的行为方式(见背景和意义)。 假设：无效假设是HPV感染的患病率和类型没有差异 HNSCC在AA和EA患者中的分布。此外，这项研究还将测试与众不同的基因 不同种族之间HPV阳性和HPV阴性癌症的表达谱特征，有助于 阐明了两个种族之间HNSCC发展机制的差异。 沿着这些思路，初步研究了HPV阳性和HPV阴性HNSCC的基因表达。 作为种子基金的一部分，我们的实验室正在进行这项和其他合作建议 HNSCC)发现的差异表达基因可能在确定不同的致病机制中发挥作用 以及这些肿瘤的临床特点。

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.