HPV IMMUNIZATION RESPONSE AND STRESS

项目概述：一种四价HPV6、11、16、18疫苗(Gardasil)已被批准用于9-26岁的妇女，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明，但该疫苗的有效性尚未在临床实践环境中进行测试。承受更大压力的患者对其他类型疫苗的免疫反应能力降低。Gardasil很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(多个终身性伴侣、从不使用避孕套、既往异常巴氏涂片、吸烟和HPV感染)或通过免疫系统的直接失调来发挥作用的。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宫颈HPV感染率更高，宫颈细胞学异常率更高，心理应激率更高。这项研究的目的是确定在接受加德西疫苗的18-26岁女性中，血清HPV6/11/16/18抗体反应是否因应激而改变。这将通过一项对432名年龄在18-26岁之间的女性的研究来实现，她们报告了从 俄亥俄州阿巴拉契亚地区。所有参与者将在基线、两个月和六个月接种Gardasil疫苗。在接种调查问卷之前，将收集与HPV暴露、危险行为和心理应激源有关的数据。宫颈样本将被收集用于细胞学和HPV检测。将在基线和12个月收集血清样本进行HPV6、11、16和18抗体检测。问卷数据和血清样本将在12个月时重复。主要的结果衡量指标是基线和12个月时血清HPV6、11、16和18抗体的差异。感兴趣的变量包括感知的压力、性行为、社会经济地位、获得医疗保健的机会(医疗保险是/不是)、吸烟、阿巴拉契亚人的自我认同、 心理神经免疫学模型中提出的HPV宫颈基线状态，以及既往宫颈细胞学异常史。在这个模型中，阿巴拉契亚人的自我认同、社会经济地位、孤独感、医疗保健途径和应对方式被认为是导致女性感知到的压力的因素。感受到的压力对加德西疫苗免疫反应的影响可以通过健康行为来实现，如终身性伴侣多(或=4)、从不使用避孕套、既往异常巴氏涂片、吸烟和接种时的HPV状态。感知到的压力可以通过造成免疫失调来对免疫反应产生直接的生理影响，这可以通过增加EBV VCA-Ig G滴度来衡量。抑郁症状可以调节感知到的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，那么我们就可以确定这种调节是否会降低疫苗的临床有效性，并研究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.