INFLAMMATORY BIOMARKERS AND HPV-ASSOCIATED ORAL PRE-CANCER

描述（由申请人提供）： 尽管癌症治疗取得了进展，但少数民族患者口腔癌发病率和死亡率的差异仍然没有改变。吸烟和饮酒是口腔癌的危险因素，然而，这些习惯不能解释所有头颈部恶性肿瘤的病例。人乳头状瘤病毒（HPV）是浸润性宫颈癌的一个公认的危险因素，也已在几个口腔癌前病变中发现。2005-2006年期间，在南加州洛杉矶县大学（LAC-USC）医学中心进行的一项使用罗氏线性阵列HPV基因分型检测进行的头颈癌和HPV筛查的初步研究表明，45%的肿瘤标本在任何时间均为HPV阳性，100%的阳性肿瘤携带HPV 16。在过去的几十年中，HPV感染已成为服务不足的社区，西班牙裔和非洲裔美国人中最流行的性传播感染之一，与其他种族群体相比。本研究的总体目标是确定HPV是否与生活在洛杉矶县的少数民族患者的口腔癌前病变和口腔癌有关，并确定炎症相关的生物标志物作为口腔癌进展的诊断和预后工具。本研究的具体目的如下：1）确定居住在洛杉矶县的少数人群（非洲裔美国人和西班牙裔美国人）中人乳头瘤病毒感染与口腔白斑之间的关联; 2）评价与HPV感染患者和口腔白斑相关的促炎和抗炎细胞因子作为口腔癌进展的生物标志物。具体目标是确定HPV相关口腔癌前病变中潜在的炎症生物标志物，可用于确定非洲裔美国人和西班牙裔人群中的高危亚组，并制定适当的干预策略，以降低这些人群中口腔癌的发病率。将使用基于医院的病例对照设计研究生活方式因素（如吸烟、饮酒和HPV感染）与遗传宿主因素之间的关系。这项试点研究的结果将导致未来的R 01应用，有可能提高癌症流行病学研究的质量，减少少数人群的口腔癌负担。

DESCRIPTION (provided by applicant): Despite advances in cancer therapy, discrepancy in the morbidity and mortality rates of oral cancer among minority patients has remained unchanged. Tobacco and alcohol consumption have been associated as risk factors in oral cancer, however, these habits fail to explain all cases of head and neck malignancy. Human papilloma virus (HPV), a well established risk factor in invasive cervical cancer, has also been identified in several oral pre-cancerous lesions. A pilot study of head and neck cancer and HPV screening using the Roche Linear Array HPV genotyping test conducted at Los Angeles County-University of Southern California (LAC- USC) medical center during 2005-2006 has demonstrated that 45% of tumor specimens were HPV positive at any time with 100% of positive tumors harboring HPV 16. In the past decades, HPV infection has become one of the most prevalent sexual transmitted infections in the underserved communities, Hispanics and African Americans, as compared to other ethnic groups. The overall objective of this study is to determine whether HPV is related to oral pre-malignant cancer and oral cancer in minority patients living in Los Angeles County and to identify inflammation-associated biomarkers as diagnostic and prognostic tools for oral cancer progression. The following specific aims will be addressed in this study: 1) To determine the association between human papilloma virus infection and oral leukoplakia among a minority population, African Americans and Hispanics, living in Los Angeles County; and 2) To evaluate pro-inflammatory and anti-inflammatory cytokines associated with HPV infected patients and oral leukoplakia as biomarkers for oral cancer progression. The specific objective is to identify potential inflammatory biomarkers in HPV-associated oral pre-cancer which may be used to identify high-risk subgroups among African American and Hispanic populations and to tailor appropriate intervention strategies to reduce the incidence of oral cancer among these populations. The relationship between lifestyle factors, such as tobacco smoking, alcohol consumption and HPV infection, and genetic host factors will be studied using a hospital-based case-control design. The findings from this pilot study will lead to a future R01 application with potential to improve the quality of cancer epidemiologic research and reduce the oral cancer burden in minority populations.