Primary HPV-based Cervical Cancer Screening Algorithms in Botswana

Study Overview
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Brief Summary
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Primary high-risk human papillomavirus (HPV) testing has become first line screening for cervical cancer in high-income countries. The feasibility of this approach in low- and middle-income countries (LMICs) is less clear, as is the role of HPV testing among women living with human immunodeficiency virus (HIV). The proposed study seeks to evaluate the accuracy of cervical cancer screening algorithms using primary HPV testing followed by various forms of visual evaluation, including visual inspection with acetic acid (VIA), colposcopy and automated visual evaluation (AVE) for the detection of high-grade cervical dysplasia, using histology as the gold standard. We will validate the AmpFire Assay for HPV self-sampling in our setting. We will determine safe screening intervals in women living with HIV (WLHIV) in an HPV-based cervical cancer screening program and compare triage strategies for positive HPV results at WHO recommended screening intervals for WLHIV. We also seek to understand in-depth the attitudes, acceptability and preferences regarding cervical cancer screening, HPV testing, and self-sampling, for women in Botswana through interviews of a sub-set of women recruited for the cervical cancer screening study. Finally, we will analyze the cost of two-stage cervical cancer screening algorithms using high-risk HPV testing in Botswana.

Official Title
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Performance of Two-stage Cervical Cancer Screening Algorithms Using Primary High-risk Human Papillomavirus Testing in Botswana

Conditions
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Cervical Cancer, Prevention

Intervention / Treatment
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* Diagnostic Test: Automated visual evaluation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cis-gender female or transgender male (must have a cervix) ≥25 years of age Competent to understand study procedures and give informed consent. Exclusion Criteria: Currently pregnant (as diagnostic procedures for cervical cancer are often deferred during pregnancy) Previous hysterectomy Previous diagnosis of cervical cancer

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Baseline screening cohort<br>This group undergoes HPV testing using self-collected swabs. Triage evaluation occurs in all women who test HPV positive which includes visual inspection with acetic acid, colposcopy and image capture for automated visual evaluation. The WLHIV in the cohort who test HPV positive at baseline but who have concurrent benign histopathology results will be invited back for re-screening at a 2-year interval, and undergo similar HPV testing and triage procedures. The WLHIV in the cohort who test HPV negative at baseline will be invited back for re-screening at a 3-year interval and undergo similar HPV testing and triage procedures. | Diagnostic Test: Automated visual evaluation<br>* Participants will undergo primary hrHPV testing and if positive will be referred for VIA per Botswana and WHO guidelines. Participants will also undergo colposcopy, image capture for automated visual evaluation and biopsy at the time of VIA.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare the sensitivity, specificity, PPV and NPV of triage of primary human papillomavirus testing with automated visual evaluation to visual inspection with acetic acid and colposcopy |  | 3 years | 
| Determine the persistence of HPV infection in WLHIV at the pre-specified follow-up interval |  | 5 years | 
| Determine the clearance of HPV infection in WLHIV at the pre-specified follow-up interval |  | 5 years | 
| Determine the incidence of HPV infection in WLHIV at the pre-specified follow-up interval |  | 5 years | 
| Quantify the persistence of cervical intraepithelial lesion grade 3 or worse in women living with HIV who were baseline HPV positive but with benign pathology at 2 year interval screening |  | 5 years | 
| Quantify the progression of cervical intraepithelial lesion grade 3 or worse in women living with HIV who were baseline HPV positive but with benign pathology at 2 year interval screening |  | 5 years | 
| Quantify the regression of cervical intraepithelial lesion grade 3 or worse in women living with HIV who were baseline HPV positive but with benign pathology at 2 year interval screening |  | 5 years | 
| Quantify the cure of cervical intraepithelial lesion grade 3 or worse in women living with HIV who were baseline HPV positive but with benign pathology at 2 year interval screening |  | 5 years | 
| Quantify the incidence of cervical intraepithelial lesion grade 3 or worse in women living with HIV who were baseline HPV positive but with benign pathology at 2 year interval screening |  | 5 years | 
| Quantify the persistence of cervical intraepithelial lesion grade 3 or worse in women living with HIV who were baseline HPV negative at 3 year interval screening |  | 5 years | 
| Quantify the progression of cervical intraepithelial lesion grade 3 or worse in women living with HIV who were baseline HPV negative at 3 year interval screening |  | 5 years | 
| Quantify the regression of cervical intraepithelial lesion grade 3 or worse in women living with HIV who were baseline HPV negative at 3 year interval screening |  | 5 years | 
| Quantify the cure of cervical intraepithelial lesion grade 3 or worse in women living with HIV who were HPV negative at 3 year interval screening |  | 5 years | 
| Quantify the incidence of cervical intraepithelial lesion grade 3 or worse in women living with HIV who were baseline HPV negative at 3 year interval screening |  | 5 years | 
| Analyze the cost of two-stage cervical cancer screening algorithms using high-risk HPV testing in Botswana. |  | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Understand in-depth the attitudes, acceptability and preferences regarding cervical cancer screening, HPV testing, and self-sampling, for women in Botswana through interviews of a sub-set of women recruited for the cervical cancer screening study. |  | 6 years | 
| Evaluate the performance of a novel HPV assay as a stand-alone screening tool in our high-prevalence HIV population |  | 3 years | 
| Evaluate the impact of patient demographic and clinical factors, such as number of sexual partners, smoking, HIV status and related HIV immune markers, on risk of cervical dysplasia |  | 5 years | 
| Evaluate the impact of patient characteristics and and risk factors on the risk for cervical disease |  | 5 years |