Genetic Resistance to Oncogenic Human Papillomaviruses

对致癌人乳头瘤病毒的遗传抗性

• 批准号: 6920326
• 负责人: STEPHEN K TYRING
• 金额: $ 6.99万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-01 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6920326
• 关键词: Hispanic Americans; Papillomavirus; cervical /vaginal smear; cervix neoplasms; clinical research; female; genetic polymorphism; genetic susceptibility; histocompatibility antigens; human subject; microorganism immunology; racial /ethnic difference; serotyping; viral carcinogenesis; women' s health

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.

描述（由申请人提供）：某些人乳头瘤病毒（HPV-16 和 -18）的感染与女性患浸润性宫颈癌有关。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。对于疫苗开发来说，重要的是有证据表明一些女性有能力“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。没有人报告过 HPV-16 和/或 18 血清阳性但巴氏涂片阴性且无 HPV DNA 的女性的 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。西班牙裔女性被选为这项研究的对象，因为她们是宫颈癌发病率最高的国家之一。在美国第三大城市德克萨斯州休斯顿，宫颈癌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 HLA 谱。我们将获得 1250 名接受年度健康检查的西班牙裔女性的 HPV 感染率和基因图谱。通过在常规体检期间额外进行一次宫颈涂片检查并抽取一瓶血液，对患者造成的额外风险很小。如果女性巴氏涂片结果呈阴性，则额外的宫颈涂片检查将用于检测是否存在 HPV-16 或 18。 对于那些具有 HPV-16 和/或 -18 抗体，但没有 HPV DNA 且未检测到 HPV 的女性如果巴氏涂片呈阴性，则将使用小瓶血液中的淋巴细胞进行 HLA 血清分型。这项研究将为完成更大规模的研究提供必要的初步数据，以比较对 HPV 感染的免疫反应的种族多样性以及决定这些免疫反应的遗传学。标准统计分析将用于估计 HLA 多态性与单基因 HPV 感染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。

项目成果

Association between HLA-DQB1 and cervical dysplasia in Vietnamese women.

HLA-DQB1 与越南女性宫颈发育不良之间的关联。

• DOI: 10.1111/j.1525-1438.2006.00459.x
• 发表时间: 2006
• 期刊: International journal of gynecological cancer : official journal of the International Gynecological Cancer Society
• 作者: Lema,C;Fuessel-Haws,AL;Lewis,LR;Rady,PL;Lee,P;Turbat-Herrera,EA;He,Q;Nguyen,LT;Tyring,SK;Dao,DD
• 通讯作者: Dao,DD