HPV IMMUNIZATION RESPONSE AND STRESS

项目概述：一种四价HPV 6,11,16,18疫苗（Gardasil）已被批准用于9-26岁的女性，以预防宫颈癌/阴道癌/外阴癌和生殖器疣。该疫苗的有效性已在临床试验环境中得到证实，但尚未在临床实践环境中对该疫苗的有效性进行测试。承受更大压力的患者对其他类型疫苗产生免疫反应的能力降低。同样的现象可能也存在于“加德西”疫苗中，但没有相关数据。心理压力对疫苗免疫反应的影响可能通过健康行为（终生多性伴侣、从未使用安全套、既往子宫颈抹片检查异常、吸烟和HPV感染）或免疫系统的直接失调来发挥作用。我们发现，与城市和郊区妇女相比，俄亥俄州阿巴拉契亚地区妇女的宫颈HPV发病率更高，宫颈细胞学异常的发病率更高，心理压力的发病率也很高。本研究的目的是确定18-26岁妇女接种加德西疫苗后，血清HPV 6/11/16/18抗体反应是否因压力而改变。这将通过一项对432名年龄在18-26岁之间的女性的研究来完成，这些女性报告了来自

Project Summary: A quadrivalent HPV 6, 11, 16, 18 vaccine (Gardasil) has been approved for use among women age 9-26 years to prevent cervical/vaginal/vulvar cancer and genital warts. The efficacy of the vaccine has been demonstrated in clinical trial settings, but the effectiveness of this vaccine has not been tested in clinical practice settings. Patients experiencing greater stress have a reduced capacity to mount an immune response to other types of vaccine. The same phenomenon is likely to exist for Gardasil, but there are no data. The impact of psychological stress on the immune response to a vaccine is proposed to act via health behaviors (multiple lifetime sexual partners, never using condoms, prior abnormal Pap smear, smoking, and HPV infection) or by direct dysregulation of the immune system. We have found higher rates of cerivical HPV in Appalachian Ohio women, higher rates of abnormal cervical cytology, and very high rates of psychological stress compared to urban and suburban women. The goal of this study is to determine if, in women age 18-26 years given Gardasil vaccine, serum HPV 6/11/16/18 antibody response is altered by stress. This will be accomplished by a study of 432 women age 18-26 years who report full range of life stressors recruited from Appalachian Ohio. All participants will receive the Gardasil vaccine at baseline, two months, and six months. Prior to vaccination questionnaire data related to HPV exposure risk behaviors and psychological stressors will be collected. Cervical samples will be collected for cytology and HPV testing. Serum samples will be collected for HPV 6, 11, 16 and 18 antibody assays at baseline and month 12. The questionnaire data and serum samples will be repeated at 12 months. The primary outcome measure is the difference in serum antibodies to HPV 6, 11, 16 and 18 at baseline and month 12. The variables of interest are perceived stress, sexual behaviors, socioeconomic status, access to health care (health insurance yes/no), smoking, Appalachian self-identity, HPV cervical status at baseline, and past history abnormal cervical cytology, as proposed in a psychoneuroimmunology model. In this model, Appalachian Self-Identity, socioeconomic status, loneliness, health care access, and coping are proposed to contribute to a woman's perceived stress. The impact of perceived stress on immune response to Gardasil vaccination can be by health behaviors such as multiple lifetime sexual partners (> or = 4), never using condoms, prior abnormal Pap smear, smoking, and HPV status at the time of vaccination. Perceived stress can have a direct physiologic impact on the immune response by creating immune dysregulation as measured by increased EBV VCA-IgG titers. Depressive symptoms can mediate the impact of perceived stress on immune function. If psychological stress is found to modulate the immune response to Gardasil, then we can determine if the modulation reduces the clinical effectiveness of the vaccine and examine methods to limit the impact of stress.