Cytokine Variants as Predictors of HPV-16 Status & Outcome of Oropharyngeal Cance

描述(由申请人提供)： 口咽鳞状细胞癌(SCCOP)的特点是局部肿瘤侵袭性，需要病态的局部区域治疗，生存率低，复发率高。尽管吸烟率有所下降，但SCCOP的发病率停滞不前，而年轻人的发病率正在上升。这些趋势可能是由于致癌性人乳头瘤病毒(HPV)在人群中的流行率上升所致。HPV+SCCOP是一种独特的流行病学、临床和分子疾病，具有潜在的独特临床行为和治疗反应。确定哪些人需要加强治疗，哪些人能够从降低治疗强度中受益，这对更有效和更少病态的治疗至关重要。 HPV的致癌亚型，主要是16型，是头颈癌的一个不同亚型的关键病因，主要是SCCOP。控制HPV清除和逃避免疫监视的炎症/免疫反应可能导致HPV相关性SCCOP的风险和可能的结果。此外，HPV+SCCOP独特的基因模式可能会混淆与临床结果的相关性。因此，我们推测这些基因可能功能区的遗传多态可能造成了HPV感染易感性的个体差异，并构成了对HPV相关临床结局的混杂效应。 在这项病例-病例比较研究中，研究对象将是300名从现有的头颈部鳞状细胞癌分子流行病学研究中回顾确定的SCCOP事件患者。R03项目的具体目标是：1)建立一个数据库，其中包括300名SCCOP患者的人口学、临床和随访信息、基因多态和HPV16DNA肿瘤状态；2)评估致炎和抗炎途径中涉及的炎症/免疫反应相关基因的基因型，作为SCCOP患者HPV16相关的易感性标志；以及3)确定这些基因在促炎和抗炎途径中的变异是否会改变SCCOP患者与HPV相关的临床结果(复发和生存)。该项目的长期目标是利用这些基因多态性作为替代标记，帮助识别HPV16感染的高危人群和/或预后不良的高危人群，以便更好地个体化预防和治疗SCCOP，提高生存和生活质量。

DESCRIPTION (provided by applicant): Squamous cell carcinoma of the oropharynx (SCCOP) is characterized by local tumor aggressiveness requiring morbid local-regional therapies with poor survival and high recurrence rates. Despite declining smoking prevalence, the incidence of SCCOP is stagnant and incidence is increasing in young adults. These trends may be due to the rising prevalence of oncogenic human papillomavirus (HPV) in the population. HPV+ SCCOP is a distinct epidemiologic, clinical, and molecular disease with potentially unique clinical behavior and treatment responses. Identification of those needing treatment intensification and those able to benefit from reduction of treatment intensity is critical to more effective and less morbid treatment. Oncogenic subtypes of HPV, principally type 16, are critical etiologic factors in a distinct subset of head and neck cancers, chiefly SCCOP. Inflammation/immune responses which control the HPV clearance and escape of immune surveillance may contribute to the risk and possibly the outcomes of HPV-associated SCCOP. In addition, the unique pattern of genetic profiles in HPV+ SCCOP might confound correlations with clinical outcome. Therefore, we speculate that genetic polymorphisms in the likely functional regions of these genes may pose individual difference in susceptibility to HPV infection and constitute the confounding effect on HPV-related clinical outcomes. In this case-case comparison study, the study subjects will be 300 patients with incident SCCOP retrospectively identified from an existing molecular epidemiologic study of squamous cell carcinoma of the head and neck. The specific aims for this R03 project are: 1) to establish a database with demographic, clinical and follow-up information, genotypes of the polymorphisms, and HPV16 DNA tumor status on 300 of these SCCOP patients, 2) to assess genotypes of Inflammation/immune response related genes involved in both pro- and anti-inflammation pathways as markers of susceptibility for HPV16 association among patients with SCCOP, and 3) To determine if variants of these genes in both pro- and anti-inflammation pathways modify HPV-related clinical outcomes (recurrence and survival) of SCCOP patients. The long-term goal of this project is to use these genetic polymorphisms as surrogate markers to help identify individuals at high risk of HPV16 infection and/or at risk for poor outcomes in order to better individualize SCCOP prevention and treatment as well as improve of both survival and quality of life.