Determinants of Participation in an Anal Cancer Prevention Trial

描述（由申请人提供）：本申请涉及广泛的挑战领域（05）比较有效性研究（CER）和特定的挑战主题，05- ca -102*癌症筛查的比较有效性研究。“参与肛门癌预防试验的决定因素”项目旨在为肛门上皮内瘤变（AIN）筛查和治疗以预防肛门癌的关键随机临床试验提供至关重要的信息。肛门癌在美国是一个日益严重的问题。在一般人群中，男性和女性每年增加约2%，在某些高危人群，如艾滋病毒阳性的男性和女性中尤其常见。在艾滋病毒阳性个体中，尽管有有效的抗逆转录病毒治疗（ART），但肛门癌的发病率继续增加。目前肛门癌在hiv阳性的男男性行为者（MSM）中的发病率可能高达137/ 100000，是目前在美国接受筛查的女性中宫颈癌发病率的10倍以上，并且高于世界范围内未接受筛查的女性中宫颈癌的最高发病率。与一般人群相比，艾滋病毒阳性妇女的肛门癌发病率几乎高出7倍。与子宫颈癌一样，肛门癌与人乳头瘤病毒（HPV）有关，并伴有一系列称为肛门上皮内瘤变（AIN）的癌前病变。宫颈癌的发病率通过宫颈细胞学筛查来识别高度宫颈上皮内瘤变（CIN）的妇女，然后对其进行治疗以防止进展为癌症，从而急剧降低。像宫颈癌一样，肛门癌可以通过治疗肛门同级的高级别AIN （HGAIN）来预防。肛门癌不可接受的高发病率与肛门癌可预防的可能性相结合，要求紧急干预。然而，目前还没有正式的指南推荐肛门筛查和治疗HGAIN。这是因为目前还没有研究证明HGAIN的筛查和治疗可以降低肛门癌的发病率。美国公共卫生服务部关于艾滋病毒阳性个体护理的指导方针目前指出，“对艾滋病毒血清阳性的男男性行为者和妇女进行肛门细胞学筛查可能是有用的预防措施。”然而，在提出肛门细胞学筛查的明确建议之前，需要对AIN 2或AIN 3的筛查和治疗方案进行研究。”该应用程序将提供支持开展此类研究的关键信息，即参与随机临床试验的决定因素，其中50%的HGAIN患者将接受筛查和治疗，50%的患者将不接受治疗。在5年期间结束时，将比较两组的肛门癌病例数。考虑到潜在的临床问题的复杂性，这些问题可能会影响人们的参与意愿，构成艾滋病流行的未被充分代表的少数群体的比例不断增加，以及每个种族/民族群体可能面临的参与问题的不同，一项严格的研究来衡量构成美国艾滋病流行的地理和种族/民族多样化群体的这些决定因素是至关重要的。因此，此应用程序的具体目标是：1。识别和评估提供者愿意转诊合格参与者的决定因素；2. 识别和评估患者参与随机对照试验的意愿和动机的决定因素；和3。根据目标1和目标2的数据分析，确定最佳的研究设计和样本量，以及招募策略。该申请是对这一挑战主题的回应，在这一挑战主题中，来自早期观察性研究的数据将与医生和患者的可接受性数据相结合，以允许关键的RCT进行。虽然这项随机对照试验的结果将为艾滋病毒阳性的男性和女性制定护理标准，但它们也将具有广泛的影响，超出艾滋病毒阳性人群的范围。结果将指导hiv阴性人群的筛查和治疗，该研究将提供临床标本的生物库，这将对理解从肛门上皮内瘤变到肛门癌进展的分子决定因素具有宝贵的价值。这些结果也将适用于了解宫颈癌进展的潜在因素，尤其重要的是，由于目前的护理标准是治疗高级别CIN以预防宫颈癌，因此不可能收集宫颈癌风险妇女的生物库。最后，本研究将有广泛的影响，通过通知策略，以提高参与临床研究的代表性不足的少数群体。7. 项目简介（针对非专业观众）艾滋病毒感染者中肛门癌的发病率高于引入常规宫颈细胞学筛查之前的宫颈癌，但与宫颈癌不同的是，目前没有针对肛门癌的筛查建议。拟议的焦点小组/调查研究对于计划在艾滋病毒阳性男性和女性中进行大规模确定的随机对照试验（RCT）至关重要，以测试通过肛门细胞学筛查确定的肛门癌前体的治疗是否可以预防肛门癌。在这项拟议研究的帮助下，计划进行的RCT将为艾滋病毒阳性的男性和女性制定护理标准，但也将对艾滋病毒阴性人群的筛查和治疗以及了解宫颈癌和肛门癌进展的潜在因素具有广泛的影响。

DESCRIPTION (provided by applicant): This application addresses broad Challenge Area (05) Comparative effectiveness research (CER) and specific Challenge Topic, 05-CA-102* Comparative Effectiveness Research on Cancer Screening. The project, "Determinants of participation in an anal cancer prevention trial" is designed to provide information that will be critical to the performance of a pivotal randomized clinical trial of screening and treatment of anal intraepithelial neoplasia (AIN) to prevent anal cancer. Anal cancer is a growing problem in the United States. Increasing by approximately 2 percent per year among both men and women in the general population, it is particularly common among certain high-risk groups such as HIV-positive men and women. Among HIV-positive individuals, the incidence of anal cancer has continued to increase despite the availability of effective anti-retroviral therapy (ART). The current incidence of anal cancer among HIV-positive men who have sex with men (MSM) may be as high as 137/100,000, or more than 10 times the current incidence of cervical cancer in the screened population of women in the U.S., and is higher than the highest incidence of cervical cancer in unscreened populations of women world-wide. The incidence of anal cancer is almost 7-fold higher among HIV-positive women compared with the general population. Like cervical cancer, anal cancer is associated with human papillomavirus (HPV) and is preceded by a series of precancerous changes known as anal intraepithelial neoplasia (AIN). The incidence of cervical cancer has been sharply reduced by screening with cervical cytology to identify women with high-grade cervical intraepithelial neoplasia (CIN), which is then treated to prevent progression to cancer. Like cervical cancer anal cancer may be preventable through treatment of the anal equivalent, high-grade AIN (HGAIN). The combination of an unacceptably high incidence of anal cancer with the likelihood that anal cancer is preventable calls for urgent intervention. At this time however, there are no formal guidelines recommending anal screening and treatment of HGAIN. This is because no studies have yet been done to demonstrate that screening for and treatment of HGAIN reduced the incidence of anal cancer. The USPHS guidelines for the care of HIV-positive individuals currently state that "anal cytology screening of HIV-seropositive MSM and of women may be useful preventive measures. However, studies of screening and treatment programs for AIN 2 or 3 need to be implemented before definitive recommendations for anal cytology screening can be made". This application will provide critical information that will support the conduct of such a study, namely determinants of participation in a randomized clinical trial in which 50 percent of participants with HGAIN will be screened and treated, and 50 percent will be observed without treatment. At the end of a 5-year period, the number of anal cancer cases will be compared in both arms. Given the complexities of the underlying clinical issues that might govern willingness to participate, the increasing proportion of underrepresented minorities that comprise the HIV epidemic and the varying issues around participation that each of these racial/ethnic groups might have, a rigorous study to measure these determinants in geographically and racially/ethnically diverse groups that comprise the HIV epidemic in the U.S. is critical. The specific aims of this application are therefore to: 1. To identify and assess the determinants of provider willingness to refer eligible participants; 2. To identify and assess the determinants of patient willingness and motivation to participate in the RCT; and 3. To determine the optimum study design and sample size, and recruitment strategies based on the analysis of data from Aims 1 and 2. This application is responsive to this challenge topic in which data from earlier observational studies would be augmented with physician and patient acceptability data to permit the pivotal RCT to proceed. Although the results of the RCT will set standard of care for HIV-positive men and women, they will also have wide implications beyond that of the HIV-positive population. The results will guide screening and treatment for HIV-negative populations as well, and the study will provide a biobank of clinical specimens that will be invaluable to understanding molecular determinants of progression from anal intraepithelial neoplasia to anal cancer. These results will also be applicable to understanding the factors underlying progression to cervical cancer, and will be particularly important since assembly of such as biobank of women at risk for cervical cancer would be currently impossible given that the standard of care is to treat high-grade CIN to prevent cervical cancer. Finally, this study will have broad influence by informing strategies to enhance participation in clinical studies by underrepresented minority groups. 7. Project Narrative (for lay audience) The incidence of anal cancer among people with HIV is higher than cervical cancer was before routine cervical cytology screening was introduced, but unlike cervical cancer, there are currently no screening recommendations in place for anal cancer. The proposed focus group/survey study will be essential to planning a large definitive randomized controlled trial (RCT) in HIV-positive men and women to test whether treatment of anal cancer precursors identified through anal cytology screening can prevent anal cancer. The RCT planned with the assistance of this proposed study will set the standard of care for HIV- positive men and women, but will also have wide implications for screening and treatment for HIV- negative populations, as well as understanding the factors underlying progression to cervical and anal cancer.