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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.

摘要