Genetic Resistance to Oncogenic Human Papillomaviruses

点击翻译按钮获取中文摘要

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.