Promoting Comprehensive Cervical Cancer Prevention and Better Women's Health in Low- and Medium Resource Settings HPV Screening With Triage by HPV Genotyping Versus Visual Inspection With Acetic Acid: a Randomized Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 5,500
- 试验地点
- 2
- 主要终点
- Sensitivity of triage by HPV genotyping and VIA/VILI for cervical intraepithelial neoplasia grade 2 or more severe (CIN2+) detection
研究概览
简要总结
Cervical cancer is the leading cause of cancer death among women in sub-Saharan Africa, despite the existence of effective prevention and screening methods. Because vaccination rates against human papillomavirus (causing nearly all cervical cancers) are still insufficient in some low-resource countries, early detection and treatment of cervical lesions at risk of progressing to cancer are crucial components of cervical cancer control. Therefore, it is essential to find the most reliable and appropriate screening strategy in the context of low-resource countries in order to identify women in need of treatment and thus prevent the development of cervical cancer. The objective of our study is to compare two different methods of cervical cancer screening adapted to low-resource settings, in two study centers in Cameroon.
详细描述
HPV used as a stand-alone test has a limited specificity and positive predictive value and as a consequence, a significant number of HPV-positive women have no cervical precancerous lesions or cancer and receive unnecessary workup and treatment. For this reason, the WHO has recommended visual inspection with acetic acid (VIA/VILI) as a triage test of HPV-positive women to identify women requiring treatment. Nevertheless, VIA is a highly subjective procedure dependent on the health care provider's experience, with diagnostic accuracy varying from setting to setting. Triage by HPV genotyping has recently emerged as an alternative to triage by VIA, with immediate treatment of women with a subset of high-risk HPV genotypes only, thus reducing overtreatment rates. However, to date, the triage of HPV-positive women by VIA versus HPV genotyping has not yet been compared. This project aims to implement primary HPV-based screening in Cameroon followed by an immediate offer for treatment by thermal ablation after randomization for triage by HPV genotyping or VIA. More specifically, we aim to determine if triage by HPV genotyping (with immediate treatment of women with HPV types 16, 18, 45, 31, 33, 35, 52 or 58) allows better targeting of women needing treatment and allocation of resources to women at-risk than triage by VIA, as recommended by the WHO.
Primary objective: To identify the most efficient screening strategy for cervical cancer in Cameroon, more specifically to determine whether triage by a pool of eight genotypes (HPV types 16, 18, 45, 31, 33, 35, 52 or 58) is more effective than triage by visual inspection with acetic acid for detection of precancerous lesions. ¨
Secondary objectives:
- To determine the overtreatment rate in each screening group (HPV genotyping and VIA/VILI)
- To determine the rate of adverse events (e.g. hemorrhage, infection, hospitalization) in each screening group
- To determine which participant characteristics may be associated with better prediction of CIN2+ for each screening group
- To assess patient and health care provider acceptability of both screening strategies
- To create a sustainable structure for the promotion of women health with a priority made in the prevention of cervical cancer West Region of Cameroon
- To treat all precancerous or cancerous lesions discovered during the screening
- To inform women and their families about gynecological pathologies, including cervical cancer, sexually transmitted diseases (STD) and HIV
- To create a database of cervical images for continuous clinical education
- To develop an Automated VIA/VILI Classifier (AVC) that can help identify cervical precancerous lesions based on a 2-minute video of the cervix during VIA/VILI
- To assess women's, the community's and healthcare providers' acceptability of the AVC test
Study Design: National multicentric open-label two-arm randomized controlled trial
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- Single (Outcomes Assessor)
盲法说明
Allocation to the study arm will be concealed until primary HPV screening by the GeneXpert machine has been performed, in order to ensure that the health care provider enrolling the participant into the study and the participant herself have no a priori knowledge of group assignment.
Detected HPV genotypes will only be revealed to the midwife executing the pelvic examination and treatment if the participant is randomized in the intervention arm (triage by genotyping), in order to know whether to treat the participant or not. If the participant is randomized in the control arm (triage by VIA), the midwife will be blinded to the exact HPV genotype channel(s) in order to avoid influence of treatment.
The pathologist performing histological analysis (gold standard) will be blinded to the study arm and the on-site diagnosis.
入排标准
- 年龄范围
- 25 Years 至 49 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •HIV-negative women aged 30-49 and HIV-positive women aged 25-49 years old
- •Ability to understand study procedures and accepting voluntarily to participate by signing an informed consent form (ICF).
排除标准
- •Pregnancy at the time of screening
- •Previous hysterectomy
- •Known cervical cancer
- •Symptoms of cervical cancer (e.g. metrorrhagia, known pelvic mass)
- •Conditions that can interfere with visualization of the cervix
- •Severe pre-existing medical conditions (e.g. advanced cancer, terminal renal failure)
- •Women who are not able to comply with the study protocol.
结局指标
主要结局
Sensitivity of triage by HPV genotyping and VIA/VILI for cervical intraepithelial neoplasia grade 2 or more severe (CIN2+) detection
时间窗: 2 years
Sensitivity of triage by HPV genotyping and VIA/VILI for cervical intraepithelial neoplasia grade 2 or more severe (CIN2+) detection at time of screening (first visit), considering histologic results (from cervical biopsy and/or endocervical brushing) as the gold-standard.
次要结局
- Estimated number of avoided cases of cervical cancer in each screening group(3 years)
- Patient and health care provider satisfaction with the screening process of each strategy(2 years)
- Percentage of participants who have correctly followed the screening, triage and treatment strategy in each study arm(2 years)
- Proportion of adverse events in each screening group(2.5 years)
- Participant characteristics associated with better prediction of CIN2+ for each screening group(2 years)
- Overtreatment rate in each screening group(2.5 years)
- Prevalence of HPV infection and cervical pre-cancer and cancer among Cameroonian women(2 years)
- Specificity, positive predictive value and negative predictive value of triage by HPV genotyping and VIA/VILI for cervical intraepithelial neoplasia(2 years)
- Number of cervical images captured by smartphone for clinical education(3 years)
研究者
Prof. Patrick Petignat
Professor
University Hospital, Geneva