Cervical Pre-cancer Treatment Failure Among Women Living With HIV in Zimbabwe: a Cohort Study
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 168
- 试验地点
- 2
- 主要终点
- Cumulative CIN2+ persistence among participants with DNA hypermethylation
研究概览
简要总结
The goal of this observational study is to improve cervical pre-cancer treatment outcomes among women living with HIV (WLWH), particularly in low and middle income countries (LMICs), by generating the evidence needed for post-treatment monitoring guidelines. The main questions it aims to answer are:
- What is the risk of disease recurrence/persistence after cervical pre-cancer treatment among women living with HIV in Zimbabwe?
- What is the predictive value of different human papillomavirus (HPV) and DNA methylation testing strategies for monitoring cervical disease recurrence/persistence after pre-cancer treatment?
Participants will have cervical biopsies taken for histological assessment and cervical samples for HPV genotyping and DNA methylation testing.
Researchers will follow all participating women every six months for 24 months to evaluate post-treatment monitoring and cervical disease outcomes.
详细描述
Background and Rationale:
Cervical cancer mortality rates in Zimbabwe are among the highest in the world. Cervical cancer disproportionally affects women living with HIV (WLWH). In 2020, the World Health Assembly adopted a strategy to eliminate cervical cancer as a public health problem. To date, global efforts to eliminate cervical cancer have focused on expanding coverage of HPV vaccination, cervical cancer screening, and treatment for cervical pre-cancerous lesions. However, without monitoring treatment outcomes and ensuring that pre-cancerous lesions were successfully removed, the ambitious goal of cervical cancer elimination may not be attainable.
Cervical disease persistence and recurrence after pre-cancer treatment are common in WLWH. Data on the accuracy of post-treatment screening tests to guide clinical management are scarce. In July 2021, the World Health Organization (WHO) released new cervical cancer screening guidelines that propose primary HPV testing for all women. For follow-up of treated WLWH, the WHO guidelines suggest HPV testing at 12 and 24 months and immediate re-treatment for those who test positive. However, HPV is highly prevalent in WLWH, and the predictive value of a positive test for high-risk HPV infection after pre-cancer treatment in WLWH is uncertain but probably low. Therefore, alternative testing strategies such as confirmation of type-specific HPV persistence, extended HPV genotyping, and combining HPV testing with DNA methylation triage need to be explored. DNA methylation occurs as HPV infection progresses to cervical pre-cancer and cancer. Thus, methylation tests may distinguish between transient and persistent HPV infections that will advance to cancer. An advantage of molecular methylation tests is that they can be automated and are less subjective than morphological tests.
Objective(s):
Primary objectives:
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Women aged 18-65 years
- •Positive HIV status confirmed through medical records
- •Positive test result for any high-risk HPV genotype at preceding cervical cancer screening visit
- •Cervical pre-cancer treatment required according to Newlands Clinic guidelines
- •Signed informed consent
排除标准
- •Women with a history or suspicion of cervical cancer
- •Women with a history of total hysterectomy (no cervix)
- •Women treated for cervical pre-cancer in the past 12 months
- •Pregnant women
结局指标
主要结局
Cumulative CIN2+ persistence among participants with DNA hypermethylation
时间窗: 24 months
Proportion of participants with histologically confirmed CIN2+ up to 24 months after pre-cancer treatment among participants with DNA hypermethylation in first post-treatment cervical samples
Cumulative CIN2+ persistence among participants with any high-risk HPV
时间窗: 24 months
Proportion of participants with histologically confirmed CIN2+ up to 24 months after pre-cancer treatment among participants with any high-risk HPV in first post-treatment cervical samples
Cumulative CIN2+ persistence
时间窗: 24 months
Proportion of participants with histologically confirmed CIN2+ up to 24 months after pre-cancer treatment
Cumulative CIN2+ persistence among participants with genotype-specific HPV persistence
时间窗: 24 months
Proportion of participants with histologically confirmed CIN2+ up to 24 months after pre-cancer treatment among participants with genotype-specific HPV persistence in first post-treatment cervical samples
Cumulative CIN2+ persistence among participants with HPV 16 or 18
时间窗: 24 months
Proportion of participants with histologically confirmed CIN2+ up to 24 months after pre-cancer treatment among participants with HPV 16 or 18 in first post-treatment cervical samples
Association of baseline factors with CIN2+ persistence
时间窗: 24 months
Analysis of whether baseline factors-including CD4 cell count, HIV RNA viral load, HPV genotype, vaginal microbiome composition, sexually transmitted infections, cervical lesion grade, or type of pre-cancer treatment-are associated with cumulative CIN2+ persistence up to 24 months after pre-cancer treatment
Cumulative CIN2+ persistence
时间窗: 6 months
Proportion of participants with histologically confirmed CIN2+ at 6 months after pre-cancer treatment
Cumulative CIN2+ persistence
时间窗: 12 months
Proportion of participants with histologically confirmed CIN2+ up to 12 months after pre-cancer treatment
Cumulative CIN2+ persistence
时间窗: 18 months
Proportion of participants with histologically confirmed CIN2+ up to 18 months after pre-cancer treatment
Cumulative CIN2+ persistence
时间窗: 24 months
Proportion of participants with histologically confirmed CIN2+ up to 24 months after pre-cancer treatment
Cumulative CIN2+ persistence among participants with genotype-specific HPV persistence
时间窗: 24 months
Proportion of participants with histologically confirmed CIN2+ up to 24 months after pre-cancer treatment among participants with genotype-specific HPV persistence in first post-treatment cervical samples
Cumulative CIN2+ persistence among participants with HPV 16 or 18
时间窗: 24 months
Proportion of participants with histologically confirmed CIN2+ up to 24 months after pre-cancer treatment among participants with HPV 16 or 18 in first post-treatment cervical samples
Cumulative CIN2+ persistence among participants with DNA hypermethylation
时间窗: 24 months
Proportion of participants with histologically confirmed CIN2+ up to 24 months after pre-cancer treatment among participants with DNA hypermethylation in first post-treatment cervical samples
Cumulative CIN2+ persistence among participants with any high-risk HPV
时间窗: 24 months
Proportion of participants with histologically confirmed CIN2+ up to 24 months after pre-cancer treatment among participants with any high-risk HPV in first post-treatment cervical samples
Association of baseline factors with CIN2+ persistence
时间窗: 24 months
Analysis of whether baseline factors-including CD4 cell count, HIV RNA viral load, HPV genotype, vaginal microbiome composition, sexually transmitted infections, cervical lesion grade, or type of pre-cancer treatment-are associated with cumulative CIN2+ persistence up to 24 months after pre-cancer treatment
次要结局
- Association of baseline factors with genotype-specific HPV persistence(24 months)
- Agreement beyond chance between HPV test results in paired cervical and urine samples(6 months)
- Agreement beyond chance between DNA methylation test results in paired cervical and urine samples(0 months (baseline))
- Agreement between beyond DNA methylation test results in paired cervical and urine samples(6 months)
- Agreement beyond chance between HPV test results in paired cervical and urine samples(0 months (baseline))
- Association of baseline factors with genotype-specific HPV persistence(24 months)
- Agreement beyond chance between HPV test results in paired cervical and urine samples(6 months)
- Agreement beyond chance between DNA methylation test results in paired cervical and urine samples(0 months (baseline))
- Agreement between beyond DNA methylation test results in paired cervical and urine samples(6 months)