Acceptability and feasibility of combination treatment for cervical precancer among South Africa women living with HIV

南非艾滋病毒感染者宫颈癌前病变联合治疗的可接受性和可行性

基本信息

批准号：
10411963
负责人：
Carla J Chibwesha
金额：
$ 22.64万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-06-01 至 2025-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10411963
关键词：
Ablation Accounting Address Adherence Adjuvant African Aftercare Area Biopsy Cervical Cervical Cancer Screening Cervical Intraepithelial Neoplasia Cessation of life Community Health Education Disease Dose Education and Outreach Enrollment Excision Fluorouracil Focus Groups Frequencies Generations Generic Drugs Genital Genitalia Genotype Goals HIV HIV-1 Health Health Personnel High Risk Woman Histology Human Papilloma Virus Vaccination Human Papillomavirus Immune Immune response Incidence Inflammation Infrastructure Interleukin-1 alpha Interleukin-10 Interleukin-12 Interview Investments Irrigation Malignant Neoplasms Malignant neoplasm of cervix uteri Measures Mediating Modality Nurses Operative Surgical Procedures Outcome Participant Patients Perception Placebos Population Prevention strategy RNA Randomized Recurrence Reporting Research Resource-limited setting Resources Risk Rural Safety Self Administration Series Sexually Transmitted Diseases South Africa South African Specimen TNF gene Testing Treatment outcome Woman acceptability and feasibility cancer prevention cancer therapy cervical cancer prevention cervicovaginal cost cytokine efficacy study efficacy testing experience feasibility trial high risk population immune activation improved lifetime risk loop electrosurgical excision procedure low and middle-income countries male mortality disparity novel premalignant prevent primary outcome screening secondary outcome standard care treatment strategy tumor-immune system interactions

项目摘要

ABSTRACT Cancer incidence, mortality, and disparities between rich and poor are projected to rise at staggering rates. It is estimated, for example, that cancer will kill one million Africans each year by 2030, with cervical cancer accounting for the most cancer deaths in African women. Global efforts to eliminate cervical cancer are currently focused on expanding access to HPV vaccination and cervical cancer screening. However, these efforts lack equal investment in treatment of precancerous cervical intraepithelial neoplasia grade 2/3 (CIN2/3), particularly among HIV-infected women. This gap leaves a generation of HIV-infected women at high risk of persistent/recurrent CIN2/3 and progression to cervical cancer because standard treatment for CIN2/3 (excision or ablation) is far less effective in this population. The need for novel treatment approaches for CIN2/3 in HIV- infected women is therefore substantial. The central hypothesis of our proposal is that topical 5-fluorouracil (5FU), a widely available low-cost generic drug, can be repurposed as a patient-controlled, adjuvant treatment for CIN2/3 after surgical excision to reduce the risk of persistent/recurrent CIN2/3 and progression to cervical cancer among HIV-infected women. Our overarching goal is to build on U.S. efficacy studies and test the acceptability and feasibility of combination treatment for CIN2/3 (i.e., surgical excision followed by self- applied adjuvant 5FU) in a low-resource setting. First, we will explore South African perspectives on current cervical cancer prevention strategies and identify barriers to and facilitators of combination treatment in the local context. We will accomplish this through a series of focus groups and in-depth interviews with diverse stakeholders (HIV-infected women, male partners, healthcare personnel). Second, and informed by our formative research, we will conduct a feasibility trial of the combination treatment strategy to determine safety, tolerability, adherence, and retention. We will randomize 180 HIV-infected women with CIN2/3 who will undergo loop excision (LEEP) followed by self-apply 5FU versus placebo (8 doses, once every 2 weeks). Women will be followed for 24 weeks. Third, to better understand the immune response to combination treatment in HIV-infected women, we will assess changes in genital HIV-1 shedding and local immune activation associated with surgical excision followed by 5FU/placebo. Our study will be conducted in South Africa, where more than 4 million women are living with HIV and women’s lifetime risk of cervical cancer is among the highest in the world. If successful, our findings will have broad relevance for HIV-infected women in both resource-rich and resource-poor regions worldwide, including rural and remote areas of the U.S.

抽象的癌症发病率、死亡率和贫富差距预计将以惊人的速度上升。例如，据估计，到 2030 年，癌症每年将导致 100 万非洲人死于宫颈癌非洲妇女癌症死亡人数最多，目前全球正在努力消除宫颈癌。重点是扩大 HPV 疫苗接种和宫颈癌筛查的覆盖范围，但这些努力缺乏。同等投资治疗 2/3 级癌前上皮内瘤变 (CIN2/3)，特别是这一差距使一代感染艾滋病毒的妇女处于高风险之中。持续性/复发性 CIN2/3 和进展为宫颈癌，因为 CIN2/3 的标准治疗（切除或消融）在该人群中的效果要差得多，因此需要针对 HIV 中的 CIN2/3 进行新的治疗方法。因此，我们建议的中心假设是局部使用 5-氟尿嘧啶。 (5FU) 是一种广泛使用的低成本仿制药，可重新用作患者自控的辅助治疗手术切除后针对 CIN2/3，以降低持续/复发 CIN2/3 和进展为宫颈癌的风险我们的首要目标是在美国的疗效研究的基础上进行测试。 CIN2/3 联合治疗的可接受性和可行性（即手术切除后自行切除）首先，我们将探讨南非对当前情况的看法。宫颈癌预防策略并确定当地联合治疗的障碍和促进因素我们将通过一系列焦点小组和对不同背景的深入访谈来实现这一目标。其次，由我们的利益相关者（感染艾滋病毒的妇女、男性伴侣、医护人员）告知。形成性研究，我们将对联合治疗策略进行可行性试验以确定安全性，我们将对 180 名患有 CIN2/3 的 HIV 感染女性进行随机分组，她们将接受治疗。环切除术 (LEEP)，然后自行应用 5FU 与安慰剂（8 剂，每 2 周一次）。第三，为了更好地了解 HIV 感染者对联合治疗的免疫反应。对于女性，我们将评估与手术相关的生殖器 HIV-1 脱落和局部免疫激活的变化我们的研究将在南非进行，那里有超过 400 万女性。如果成功的话，艾滋病毒感染者和女性终生患宫颈癌的风险是世界上最高的。我们的研究结果对于资源丰富和资源贫乏地区的艾滋病毒感染妇女具有广泛的相关性世界各地，包括美国的农村和偏远地区