HPV IMMUNIZATION RESPONSE AND STRESS

项目摘要：四价HPV 6，11，16，18疫苗（Gardasil）已被批准用于9-26岁的妇女，以预防宫颈/阴道/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，但该疫苗的有效性尚未在临床实践环境中得到检验。经历更大压力的患者对其他类型疫苗的免疫反应能力降低。Gardasil可能存在同样的现象，但没有数据。心理压力对疫苗免疫反应的影响被认为是通过健康行为（多个终生性伴侣，从不使用避孕套，先前异常的巴氏涂片，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妇女的宫颈HPV感染率更高，宫颈细胞学异常率更高，心理压力也非常高。这项研究的目的是确定在18-26岁的女性中，接种Gardasil疫苗后，血清HPV 6/11/16/18抗体反应是否会因压力而改变。这将通过一项对432名年龄在18-26岁之间的妇女的研究来完成，这些妇女报告了从1999年至2000年期间招募的各种生活压力源。 阿巴拉契亚俄亥俄州。所有参与者将在基线、两个月和六个月时接种Gardasil疫苗。疫苗接种前，将收集与HPV暴露风险行为和心理压力源相关的问卷数据。将采集宫颈样本进行细胞学和HPV检测。将在基线和第12个月采集血清样本进行HPV 6、11、16和18抗体检测。将在12个月时重复调查问卷数据和血清样本。主要结局指标是基线和第12个月时HPV 6、11、16和18血清抗体的差异。感兴趣的变量是感知压力，性行为，社会经济地位，获得医疗保健（健康保险是/否），吸烟，阿巴拉契亚自我认同， 根据心理神经免疫学模型的建议，基线时HPV宫颈状态和既往宫颈细胞学异常史。在这个模型中，阿巴拉契亚自我认同，社会经济地位，孤独，医疗保健的访问，和应对提出了一个女人的感知压力。感知压力对Gardasil疫苗免疫反应的影响可以通过健康行为来实现，例如多个终生性伴侣（>或= 4），从不使用避孕套，之前异常的巴氏涂片，吸烟和接种疫苗时的HPV状态。感知到的压力可以通过产生免疫失调对免疫应答产生直接的生理影响，如通过增加的EBV VCA-IgG滴度所测量的。抑郁症状可以介导感知压力对免疫功能的影响。如果发现心理压力可以调节对Gardasil的免疫反应，那么我们可以确定这种调节是否会降低疫苗的临床有效性，并检查限制压力影响的方法。

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.