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

描述(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，感染本身并不是在所有情况下都会导致癌症。数据表明，免疫因素在控制宫颈疾病进展中发挥着核心作用。研究表明，T细胞对特定的HPV16多肽的增殖反应受损与HPV感染和持续性宫颈疾病的未能消除有关。免疫功能和颈椎病之间的关系特别相关，因为有以下一组观察：1)收到异常的巴氏试验结果是一种应激事件，可能导致主要生活领域更多的痛苦和干扰；2)对应激的心理反应与免疫变化有关。在过去的几年里，我们一直在对宫颈发育不良妇女中T细胞对特定HPV16多肽的心理社会和行为反应的相关性进行初步研究。我们的发现表明，更高水平的压力与T细胞对HPV的反应受损有关，即使在控制了关键的行为风险因素后也是如此。然而，心理社会因素对HPV特异性免疫反应的任何因果效应仍有待证实。因此，在一项随机试验中，我们计划评估一项完善的、标准化的基于正念的压力减轻(MBSR)计划对宫颈发育不良妇女的生物行为影响。MBSR在不同的社会经济和文化群体中非常容易获得，并已显示出对各种患者和健康人群的心理社会和情绪健康的有益影响。在这项拟议的研究中，300名患有宫颈发育不良的妇女将被随机分配到MBSR计划或注意力控制条件下。这项研究的主要目的是考察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HPV16E6、E7和L1多肽的反应，HPV刺激的T细胞内细胞因子的表达)的影响，并与干预后和后续时间点的对照条件进行比较。据假设，与对照组参与者相比，MBSR参与者在干预后和后续的时间点将报告更低的感知压力水平、更高的生活质量和增强的HPV特异性免疫反应(即对HPV16的更大增殖反应和更多Th1细胞因子的表达)。第二个目标是检查心理社会幸福感的变化在多大程度上可能中介干预对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检查心理社会因素是否可以直接影响负责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女性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.