Genetic Resistance to Oncogenic Human Papillomaviruses

描述(由申请人提供)：感染某些人乳头瘤病毒(HPV-16和-18)与女性浸润性宫颈癌的发展有关。为了开发一种预防HPV-16和HPV-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。一些妇女有能力“清除”或根除HPV病毒，这对疫苗的开发很重要。人类白细胞抗原(HLAs)可能在识别HPV感染免疫应答的生物标志物中发挥作用。还没有人报告HPV-16和/或-18血清阳性、但巴氏涂片阴性、没有HPV DNA的妇女的人类白细胞抗原分型。也有一些迹象表明，对HPV-16和-18感染的免疫反应可能因种族而异。西班牙裔女性之所以被选入这项研究，是因为她们是宫颈癌发病率最高的人群之一。在美国第三大城市得克萨斯州的休斯顿，宫颈癌的发病率是全国最高的城市之一。我们的目标是确定成功清除HPV感染的女性的人类白细胞抗原特征。我们将获得1250名接受年度妇女健康检查的西班牙裔妇女的HPV感染率和基因图谱。通过在常规体检中再做一次宫颈涂片和抽取一瓶血，患者面临的额外风险很小。如果一名妇女的巴氏涂片呈阴性，额外的宫颈涂片将被用来检测是否存在HPV-16或HPV-18。对于那些HPV-16和/或-18抗体阳性的妇女，但没有HPV DNA，巴氏涂片阴性的妇女，将使用从血瓶中提取的淋巴细胞进行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感染免疫反应中的种族多样性和决定这些免疫反应的遗传学。标准的统计分析将被用来评估人类白细胞抗原多态与单基因HPV感染的遗传耐药性之间的关联。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.