Uterine Cervical NeoplasmsNCT07202936
Cervical Pre-cancer Treatment Failure Among Women Living With HIV in Zimbabwe
An observational study of Uterine Cervical Neoplasms and HIV I Infection, run by University of Bern at 1 site in Zimbabwe.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years, women only
- Conditions the study is for
- Uterine Cervical Neoplasms, HIV I Infection, HPV Infection
- How many people
- 168 participants
- Where
- 1 siteZimbabwe
- Study dates
- 3 May 2024to 1 Apr 2028
- How long will I take part?
- 2 Years
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- Women only
- No healthy volunteers
- Adult, Older adult
Study population: Women living with HIV who are high-risk HPV positive and need cervical pre-cancer treatment
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Cervical Pre-cancer Treatment Failure Among Women Living With HIV in Zimbabwe: a Cohort Study
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?
Read more
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.
Read the 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
- Keywords
- Cervical pre-cancer treatment, Women living with HIV, Zimbabwe, DNA methylation
- Medical subject headings
- Uterine Cervical Neoplasms, Papillomavirus Infections
What is being measured
The primary outcome is the main question the study is designed to answer.
Cumulative CIN2+ persistence
Proportion of participants with histologically confirmed CIN2+ at 6 months after pre-cancer treatment
Measured: 6 months
Cumulative CIN2+ persistence
Proportion of participants with histologically confirmed CIN2+ up to 12 months after pre-cancer treatment
Measured: 12 months
Cumulative CIN2+ persistence
Proportion of participants with histologically confirmed CIN2+ up to 18 months after pre-cancer treatment
Measured: 18 months
Cumulative CIN2+ persistence
Proportion of participants with histologically confirmed CIN2+ up to 24 months after pre-cancer treatment
Measured: 24 months
Cumulative CIN2+ persistence among participants with genotype-specific HPV persistence
Proportion of participants with histologically confirmed CIN2+ up to 24 months after pre-cancer treatment among participants with genotype-specific HPV persistence in first post-treatment cervical samples
Measured: 24 months
Cumulative CIN2+ persistence among participants with HPV 16 or 18
Proportion of participants with histologically confirmed CIN2+ up to 24 months after pre-cancer treatment among participants with HPV 16 or 18 in first post-treatment cervical samples
Measured: 24 months
Cumulative CIN2+ persistence among participants with DNA hypermethylation
Proportion of participants with histologically confirmed CIN2+ up to 24 months after pre-cancer treatment among participants with DNA hypermethylation in first post-treatment cervical samples
Measured: 24 months
Cumulative CIN2+ persistence among participants with any high-risk HPV
Proportion of participants with histologically confirmed CIN2+ up to 24 months after pre-cancer treatment among participants with any high-risk HPV in first post-treatment cervical samples
Measured: 24 months
Association of baseline factors with CIN2+ persistence
Analysis of whether baseline factors-including CD4 cell count, HIV RNA viral load, HPV genotype, vaginal microbiome composition, sexually transmitted infections, cervical lesion grade, or type of pre-cancer treatment-are associated with cumulative CIN2+ persistence up to 24 months after pre-cancer treatment
Measured: 24 months
Secondary outcomes (5)
Association of baseline factors with genotype-specific HPV persistence
Analysis of whether baseline factors-including CD4 cell count, HIV RNA viral load, HPV genotype, vaginal microbiome composition, sexually transmitted infections, cervical lesion grade, or type of pre-cancer treatment-are associated with genotype-specific HPV persistence up to 24 months after pre-cancer treatment
Measured: 24 months
Agreement beyond chance between HPV test results in paired cervical and urine samples
Agreement between paired cervical and urine samples for HPV detection (type-specific and high-risk), measured before treatment and accounting for expected agreement by chance
Measured: 0 months (baseline)
Agreement beyond chance between HPV test results in paired cervical and urine samples
Agreement between paired cervical and urine samples for HPV detection (type-specific and high-risk), measured 6 months after treatment and accounting for expected agreement by chance
Measured: 6 months
Agreement beyond chance between DNA methylation test results in paired cervical and urine samples
Agreement between paired cervical and urine samples for DNA methylation testing, measured before treatment and accounting for expected agreement by chance
Measured: 0 months (baseline)
Agreement between beyond DNA methylation test results in paired cervical and urine samples
Agreement between paired cervical and urine samples for DNA methylation testing, measured 6 months after treatment and accounting for expected agreement by chance
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Oct 2025
- Study start3 May 2024
- Primary completion1 Apr 2028 (estimated)
- Study completion1 Apr 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Uterine Cervical NeoplasmsStudies of the same condition, open and under way.
- More trials run by University of BernThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 168 participants (actual)
- Target duration
- 2 Years
Sponsor and investigators
- Lead sponsor
- University of Bern
- Sponsor type
- University, hospital or other
- Collaborators
- Krebsforschung Schweiz, Bern, Switzerland, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH)
- Responsible party
- Sponsor
- Investigators
- Margaret Pascoe, MD, Principal investigator, Newlands Clinic Women's Health Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07202936
- Sponsor's protocol ID
- 2023-00923
- Other IDs
- U01AI069924, 2023
- Status last verified
- Jun 2026
- First submitted
- 15 Jul 2025
- Last updated
- 26 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cervical Pre-cancer Treatment Failure Among Women Living With HIV in Zimbabwe: a Cohort Study
- ClinicalTrials.gov ID
- NCT07202936
- Acronym / sponsor ID
- 2023-00923
- Conditions
- Uterine Cervical Neoplasms, HIV I Infection, HPV Infection
- Keywords
- Cervical pre-cancer treatment, Women living with HIV, Zimbabwe, DNA methylation
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 168 participants (actual)
- Lead sponsor
- University of BernUniversity, hospital or other
- Collaborators
- Krebsforschung Schweiz, Bern, Switzerland, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH)
- Study start
- 3 May 2024 (actual)
- Primary completion
- 1 Apr 2028 (estimated)
- Study completion
- 1 Apr 2028 (estimated)
- First posted
- 2 Oct 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 2 Years
Who may qualify
- Ages
- 18 to 65 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Women living with HIV who are high-risk HPV positive and need cervical pre-cancer treatment
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Cumulative CIN2+ persistence
Time frame: 6 months
Proportion of participants with histologically confirmed CIN2+ at 6 months after pre-cancer treatment
Cumulative CIN2+ persistence
Time frame: 12 months
Proportion of participants with histologically confirmed CIN2+ up to 12 months after pre-cancer treatment
Cumulative CIN2+ persistence
Time frame: 18 months
Proportion of participants with histologically confirmed CIN2+ up to 18 months after pre-cancer treatment
Cumulative CIN2+ persistence
Time frame: 24 months
Proportion of participants with histologically confirmed CIN2+ up to 24 months after pre-cancer treatment
Cumulative CIN2+ persistence among participants with genotype-specific HPV persistence
Time frame: 24 months
Proportion of participants with histologically confirmed CIN2+ up to 24 months after pre-cancer treatment among participants with genotype-specific HPV persistence in first post-treatment cervical samples
Cumulative CIN2+ persistence among participants with HPV 16 or 18
Time frame: 24 months
Proportion of participants with histologically confirmed CIN2+ up to 24 months after pre-cancer treatment among participants with HPV 16 or 18 in first post-treatment cervical samples
Cumulative CIN2+ persistence among participants with DNA hypermethylation
Time frame: 24 months
Proportion of participants with histologically confirmed CIN2+ up to 24 months after pre-cancer treatment among participants with DNA hypermethylation in first post-treatment cervical samples
Cumulative CIN2+ persistence among participants with any high-risk HPV
Time frame: 24 months
Proportion of participants with histologically confirmed CIN2+ up to 24 months after pre-cancer treatment among participants with any high-risk HPV in first post-treatment cervical samples
Association of baseline factors with CIN2+ persistence
Time frame: 24 months
Analysis of whether baseline factors-including CD4 cell count, HIV RNA viral load, HPV genotype, vaginal microbiome composition, sexually transmitted infections, cervical lesion grade, or type of pre-cancer treatment-are associated with cumulative CIN2+ persistence up to 24 months after pre-cancer treatment
5 secondary outcomes
Association of baseline factors with genotype-specific HPV persistence
Time frame: 24 months
Agreement beyond chance between HPV test results in paired cervical and urine samples
Time frame: 0 months (baseline)
Agreement beyond chance between HPV test results in paired cervical and urine samples
Time frame: 6 months
Agreement beyond chance between DNA methylation test results in paired cervical and urine samples
Time frame: 0 months (baseline)
Agreement between beyond DNA methylation test results in paired cervical and urine samples
Time frame: 6 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jun 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Margaret Pascoe, MD principal investigator
Newlands Clinic Women's Health Centre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Uterine Cervical Neoplasms and HIV I Infection, run by University of Bern at 1 site in Zimbabwe.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 26 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Zimbabwe. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cumulative CIN2+ persistence (time frame: 6 months). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jun 2026.