Effects of Mindfulness-Based Stress Reduction (MBSR) on Immune Response to HPV

描述（由申请人提供）：人乳头瘤病毒（HPV）感染是宫颈癌的主要危险因素。然而，感染并不会在所有病例中导致癌症。数据表明，免疫因素在控制宫颈疾病进展中起着核心作用。研究表明，对特定HPV16肽的t细胞增殖反应受损与HPV感染和持续性宫颈疾病的解决失败有关。鉴于以下观察结果，免疫功能与宫颈疾病之间的关系尤其相关：1)收到异常的巴氏试验结果是一种压力事件，可导致主要生活领域的痛苦和中断增加；2)对应激的心理反应与免疫变化有关。在过去的几年中，我们已经对宫颈发育不良女性中t细胞对特定HPV16肽反应的社会心理和行为相关性进行了初步研究。我们的研究结果表明，即使在控制了关键的行为风险因素之后，高水平的压力与受损的t细胞对HPV的反应有关。然而，社会心理因素对hpv特异性免疫反应的因果影响仍有待证实。因此，在一项随机试验中，我们计划评估一个完善的、标准化的正念减压（MBSR）计划对宫颈发育不良妇女的生物行为影响。正念减压在不同的社会经济和文化群体中都很容易获得，并已证明对各种患者和健康人群的心理社会和情感健康有有益的影响。在拟议的研究中，300名患有宫颈发育不良的女性将被随机分配到正念减压计划或注意力控制组。该研究的主要目的是在干预后和随访时间点，与对照组相比，研究MBSR对心理社会健康（例如，感知压力，生活质量）和hpv特异性免疫功能（例如，T细胞对HPV16 E6， E7和L1肽的反应，hpv刺激的T细胞内细胞因子表达）的影响。假设在干预后和随后的随访时间点，与对照组相比，MBSR参与者将报告更低水平的感知压力，更高的生活质量，以及增强的hpv特异性免疫反应（即对HPV16的更大增殖反应和Th1细胞因子的更大表达）。第二个目的是检查社会心理健康的变化在多大程度上可能介导干预对HPV特异性免疫反应的任何影响。相关性：拟议的项目将是第一个研究社会心理因素是否能直接影响控制宫颈疾病的生物过程的项目之一。这些发现将对宫颈癌高危妇女的管理具有临床意义。

DESCRIPTION (provided by applicant): Human papillomavirus (HPV) infection is a primary risk factor for cervical cancer. However, infection alone does not lead to cancer in all cases. Data suggest that immune factors play a central role in controlling cervical disease progression. Studies have shown that an impaired T-cell proliferative response to specific HPV16 peptides is associated with a failure to resolve HPV infection and persistent cervical disease. The relation between immune function and cervical disease is particularly relevant given the following set of observations: 1) Receipt of an abnormal Pap test result is a stressful event that can lead to increased distress and disruptions in major life areas; and 2) Psychological responses to stress are associated with immunologic changes. Over the past few years, we have been conducting preliminary studies of psychosocial and behavioral correlates of T-cell response to specific HPV16 peptides among women with cervical dysplasia. Our findings suggest that higher levels of stress are associated with an impaired T-cell response to HPV, even after controlling for key behavioral risk factors. However, any causal effects of psychosocial factors on HPV-specific immune response still remain to be demonstrated. Therefore, in a randomized trial, we plan to evaluate the biobehavioral effects of a well-established, standardized Mindfulness-Based Stress Reduction (MBSR) program in women with cervical dysplasia. MBSR is highly accessible across diverse socioeconomic and cultural groups and has demonstrated beneficial effects on psychosocial and emotional well-being in a variety of patient and healthy populations. In the proposed study, 300 women with cervical dysplasia will be randomly assigned to the MBSR program or an attention control condition. The primary aims of the study are to examine the effects of MBSR on psychosocial well-being (e.g., perceived stress, quality of life) and HPV-specific immune functioning (e.g., T-cell response to HPV16 E6, E7, and L1 peptides, intracellular cytokine expression in HPV-stimulated T cells) compared to the control condition at post-intervention and follow-up time points. It is hypothesized that MBSR participants will report lower levels of perceived stress, higher quality of life, and enhanced HPV-specific immune response (i.e. greater proliferative response to HPV16 and greater expression of Th1 cytokines) compared to control participants at post-intervention and subsequent follow-up time points. A secondary aim is to examine the extent to which changes in psychosocial well-being may mediate any effects of the intervention on HPV- specific immune response. RELEVANCE: The proposed project will be one of the first to examine whether psychosocial factors can directly influence the biological processes that are responsible for controlling cervical disease. Such findings would have clinical implications for the management of women at risk for cervical cancer.