Cervical Pre-cancer Treatment Failure Among Women Living With HIV in Zimbabwe

NCT ID: NCT07202936

Last Updated: 2025-10-02

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 250 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2024-05-03
• Study Completion Date: 2027-04-01

Brief Summary

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.

Detailed Description

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:

• To estimate the risk of persistent/recurrent Cervical Intraepithelial Neoplasia grade 2 or 3 (CIN2+) at 6, 12, 18, and 24 months after pre-cancer treatment.
• To determine the accuracy and predictive value of the following HPV testing strategies in cervical samples for detection of post-treatment CIN2+ recurrence/persistence among WLWH: i) HPV type-specific persistence, ii) HPV genotyping algorithms, iii) DNA methylation testing, and iv) testing for any high-risk HPV.

Main secondary objectives:

• To identify predictors for persistent/recurrent CIN2+.
• To determine the accuracy and predictive value of different HPV and DNA methylation testing strategies in urine samples for detection of post-treatment CIN2+.
• To examine the agreement of HPV and DNA methylation results between cervical and urine samples.

Study design:

The project will analyze data from a prospective cohort study of 250 WLWH aged 18-65 years treated for cervical pre-cancer at the Newlands Clinic Women's Health Centre in Harare, Zimbabwe. The cohort study will follow all women every six months for 24 months to evaluate post-treatment monitoring and cervical disease outcomes.

Conditions

Uterine Cervical Neoplasms; HIV I Infection; HPV Infection

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Krebsforschung Schweiz, Bern, Switzerland

OTHER

Sponsor Role: collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: collaborator

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

University of Bern

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Margaret Pascoe, MD

Role: PRINCIPAL_INVESTIGATOR

Newlands Clinic Women's Health Centre

Locations

Women's Health Centre at Newlands Clinic

Harare, , Zimbabwe

Site Status: RECRUITING

Countries

Zimbabwe

Central Contacts

Eliane Rohner, MD, MSc

Role: CONTACT

eliane.rohner@unibe.ch

+41 31 684 35 23

Facility Contacts

Margaret Pascoe

Role: primary

MargaretP@newlandsclinic.org.zw

+263 772 224 093

Other Identifiers

U01AI069924

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2023-00923

Identifier Type: -

Identifier Source: org_study_id