Primary HPV-based Cervical Cancer Screening Algorithms in Botswana

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Cervical Cancer; Prevention
• Intervention / Treatment: Diagnostic test: Automated visual evaluation

• Study Type: Interventional
• Enrollment (Actual): 3000
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Botswana
  • Ramotswa, Botswana
    • Bamalete Lutheran Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 23 years to 98 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Cis-gender female or transgender male (must have a cervix)
2. ≥25 years of age
3. Competent to understand study procedures and give informed consent.

Exclusion Criteria:

1. Currently pregnant (as diagnostic procedures for cervical cancer are often deferred during pregnancy)
2. Previous hysterectomy
3. Previous diagnosis of cervical cancer

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Baseline screening cohort; 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; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Beth Israel Deaconess Medical Center
• Collaborators: University of Botswana; Botswana Harvard AIDS Institute Partnership

Study record dates

Study Major Dates

• Study Start (Actual): February 22, 2021
• Primary Completion (Anticipated): February 1, 2026
• Study Completion (Anticipated): February 1, 2027

Study Registration Dates

• First Submitted: January 23, 2020
• First Submitted That Met QC Criteria: January 24, 2020
• First Posted (Actual): January 27, 2020

Study Record Updates

• Last Update Posted (Actual): April 26, 2023
• Last Update Submitted That Met QC Criteria: April 24, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Diseases; Uterine Cervical Neoplasms
• Other Study ID Numbers: 2019P001130

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No