Primary HPV-based Cervical Cancer Screening Algorithms in Botswana

NCT04242823 | Active Not Recruiting

• 1 other identifier: 2019P001130
• Study Type: interventional
• Target: 3,000
• Locations: 1 country
• Sites: 1

Brief Summary

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 HPV genotype restriction 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 evaluate optimal 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.

Conditions

Cervical Cancer; Prevention

Outcome Measures

Primary Outcomes (7)

• Compare the sensitivity, specificity, PPV and NPV of triage of primary human papillomavirus testing with 8-type HPV genotype restriction 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 incidence of cervical intraepithelial lesion grade 2 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 2 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 Outcomes (4)

• 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 incidence of cervical dysplasia

  5 years

Study Arms (1)

Baseline screening cohort

OTHER

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 and colposcopy. 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: 8-type HPV genotype restriction

Interventions

8-type HPV genotype restriction DIAGNOSTIC_TEST

Participants will undergo primary hrHPV testing and if positive will be referred for VIA per Botswana and WHO guidelines. Participants will also undergo colposcopy and biopsy at the time of VIA. The performance of triage with 8-type HPV genotype restriction will be evaluated.

Baseline screening cohort

Eligibility Criteria

• Age: 25 Years - 100 Years
• Gender Eligibility Details: Cis-gender female or transgender male are eligible if they have a cervix.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Currently pregnant (as diagnostic procedures for cervical cancer are often deferred during pregnancy)
• Previous hysterectomy
• Previous diagnosis of cervical cancer

Sponsors & Collaborators

• Botswana Harvard AIDS Institute Partnership: collaborator
• Beth Israel Deaconess Medical Center: lead
• University of Botswana: collaborator

Study Sites (1)

Bamalete Lutheran Hospital

Ramotswa, Botswana

Location

Related Publications (2)

• Luckett R, Zhang BX, Gompers A, George J, Modest A, Bazzett-Matabele L, Vuylsteke P, Kula M, Monare B, Botha MH, Shapiro RL, Ramogola-Masire D, Grover S. High-grade cervical disease and cervical cancer in women aged 50 years and older compared with younger women: examining prevalence by HIV status in two large prospective cohorts in Botswana. BMJ Open. 2024 Oct 29;14(10):e089375. doi: 10.1136/bmjopen-2024-089375.

  PMID: 39477271 DERIVED

• Luckett R, Ramogola-Masire D, Gompers A, Moraka N, Moyo S, Sedabadi L, Tawe L, Kashamba T, Gaborone K, Mathoma A, Noubary F, Kula M, Grover S, Dreyer G, Botha MH, Makhema J, Shapiro R, Hacker MR. Triage of HPV positivity in a high HIV prevalence setting: A prospective cohort study comparing visual triage methods and HPV genotype restriction in Botswana. Int J Gynaecol Obstet. 2024 May;165(2):507-518. doi: 10.1002/ijgo.15225. Epub 2023 Nov 10.

  PMID: 37950533 DERIVED

MeSH Terms

Conditions

Uterine Cervical Neoplasms

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Obstetrician Gynecologist

Study Record Dates

• First Submitted: January 23, 2020
• First Posted: January 27, 2020
• Study Start: February 22, 2021
• Primary Completion: February 1, 2026
• Study Completion (Estimated): February 1, 2027
• Last Updated: April 27, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

BO (1)