Genetic Resistance to Oncogenic Human Papillomaviruses

描述（由申请人提供）：某些人乳头瘤病毒（HPV-16和-18）感染与女性浸润性宫颈癌的发生有关。为了开发预防HPV-16和-18的疫苗，必须分析人类对HPV的免疫反应及其潜在的遗传基础。对于疫苗的开发来说，重要的是证明一些妇女有能力“清除”或根除HPV病毒。人类白细胞抗原（HLA）可能在识别HPV感染免疫反应的生物标志物中发挥作用。还没有人报道过在HPV-16和/或-18血清阳性但巴氏涂片阴性且无HPV DNA的妇女中进行HLA分型。还有一些迹象表明，对HPV-16和-18感染的免疫反应可能因种族而异。西班牙裔妇女被选为这项研究的对象，因为她们是宫颈癌发病率最高的人群之一。在美国第三大城市德克萨斯州的休斯顿，宫颈癌发病率是全国最高的国家之一。我们的目的是确定成功清除HPV感染的女性的HLA谱。我们将获得1250名西班牙裔妇女的HPV感染率和遗传特征，这些妇女正在接受年度健康妇女检查。在常规体检中，多做一次宫颈涂片和多抽一瓶血，对病人的额外风险很小。如果一个女人有一个阴性的巴氏涂片，额外的宫颈涂片将用于检测HPV-16或18的任何存在。对于那些有HPV-16和/或-18抗体，但没有HPV DNA和阴性巴氏涂片的女性，将使用小瓶血液中的淋巴细胞进行HLA血清分型。这项研究将提供完成更大规模研究所需的初步数据，以比较HPV感染免疫反应的种族多样性和决定这些免疫反应的遗传学。标准的统计分析将用于评估HLA多态性与单基因HPV感染的遗传抗性之间的关联。因此，这项研究是开发预防感染的HPV疫苗的重要一步。

DESCRIPTION (provided by applicant): Infection with certain human papillomaviruses (HPV-16 and -18) has been associated with the development of invasive cervical cancer in women. To develop a vaccine to prevent HPV-16 and -18, the human immune response to HPV and its underlying genetic bases must be profiled. Important to the development of a vaccine is the documentation that some women have the capability to "clear" or eradicate HPV virus. Human leukocyte antigens (HLAs) may play a role in identifying biomarkers for the immune response to HPV infection. No one has ever reported typing of HLA in women who are seropositive for HPV-16 and/or-18, but who have negative Pap smears and no HPV DNA. There is also some indication that immune response to HPV-16 and -18 infections may vary by ethnic group. Hispanic women were selected for this study because they have one of the highest rates of cervical cancer. In Houston, Texas, the third largest city in the U.S., the rate for cervical cancer is one of the highest in the country. Our aim is to determine the HLA profile of women who have successfully cleared HPV infection. We will obtain HPV-infection rate and genetic profiles of 1250 Hispanic women undergoing their annual well-woman examination. By taking one additional cervical smear and drawing one additional vial of blood during the routine physical, additional risk to the patient is small. If a woman has a negative Pap smear, the additional cervical smear will be used to detect any presence of HPV-16 or 18. For those women with antibodies to HPV-16 and/or -18, but who have no HPV DNA and a negative Pap smear, HLA serotyping will be done using the lymphocytes from the vial of blood. This study will provide the preliminary data necessary to complete larger studies to compare ethnic diversity in the immune response to HPV infection and the genetics determining those immune responses. Standard statistical analyses will be used to estimate the association between HLA polymorphism and genetic resistance to monogenic HPV infection. Thus, this study is an important step in the development of an HPV vaccine to prevent infection.