2-stage Cervical Cancer Screening in Botswana

May 4, 2020 updated by: Rebecca Luckett, Beth Israel Deaconess Medical Center

Development of a Two-stage Cervical Cancer Screening Algorithm for Botswana

Cervical cancer is the leading cause of cancer death among women in Botswana. The burden of cervical cancer is largely related to the high prevalence of HIV in Botswana (22%), as HIV is known to be a significant risk factor for cervical cancer. Cervical cancer screening is life-saving and has been shown to reduce cervical cancer incidence in multiple settings. Yet, there is no consensus on appropriate screening algorithms for women living with HIV, across resource settings. Botswana is in a unique position, relative to its neighbors in Sub-Saharan Africa, in that there exists capacity for advanced screening modalities, including primary high risk human papilloma virus (hrHPV) testing and cytology-based screening. To address this issue, this study seeks to evaluate two-stage cervical cancer screening algorithms for women living with HIV in Botswana using hrHPV testing. The protocols include hrHPV testing followed by Pap Smear evaluation, VIA and colposcopy. These same participants will be invited back at one-year for cervical cancer screening using hrHPV testing (followed by triage testing) in order to inform guidelines on the frequency of HPV testing in women living with HIV. The evidence generated will be critical to guiding cervical cancer screening in HIV-infected women across resource settings.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Cervical cancer screening programs vary across settings and there is no clear guidance for effective screening programs for HIV-positive women. Evaluating the performance of algorithms that include human papillomavirus (HPV) DNA testing as first stage screening in high HIV prevalence settings like Botswana is essential for establishing an evidence-based strategy for cervical cancer screening in HIV-positive women.

This study seeks to evaluate the performance of two-stage cervical cancer screening algorithms using primary HPV testing in women living with HIV in Botswana. Second stage screening modalities include Papanicolaou (Pap) smear, visual inspection with acetic acid (VIA) and colposcopy.

The study will enroll 300 HIV positive women. For all 300 participants, gynecologic speculum exam will be performed and provider-collected cervical swabs will be collected for HPV testing and Pap smear preparation. HPV testing will be performed with either the commercially-available Cepheid Xpert® HPV Assay or a high throughput PCR platform. Pap smear will be prepared using standard technique at the site of collection.

Participants who test HPV-negative will have their Pap smear sent to the National Health Lab (NHL) for staining and pathologist evaluation. If the Pap smear is abnormal, they will be referred to colposcopy per current Botswana Cervical Cancer Prevention Guidelines.

Participants who test HPV-positive will also have their Pap smear reviewed, and will also be asked to return for colposcopy and will undergo further diagnosis and treatment for cervical cancer per national guidelines. At the colposcopy visit, a trained nurse will conduct VIA using the Botswana standard protocol. After application of acetic acid to the cervix, the nurse will record visual results as positive or negative. If VIA is positive based on assessment of the lesion(s), the nurse will record a recommendation for either cryotherapy or loop electrosurgical excision procedure (LEEP). Since all of these HPV-positive participants will undergo colposcopy, the participants will not be informed of the VIA results, as neither cryotherapy nor LEEP will be administered based on the VIA results. Rather, the participants will proceed to colposcopy and results of colposcopy will determine further diagnosis and treatment. This design enables us to assess the utility of the two-stage algorithms while providing the highest-quality follow-up to cervical cancer screening abnormalities in Botswana.

These same participants will be invited back at one-year for repeat cervical cancer screening using the same screening methods as at baseline. The data will inform guidelines on the frequency of hrHPV testing in women living with HIV.

Study Type

Interventional

Enrollment (Actual)

239

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Botswana
      • Gaborone, Botswana
        • Princess Marina Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

25 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • ≥25 years of age
  • HIV-positive
  • Competent to understand study procedures and give informed consent.

Exclusion Criteria:

  • Currently pregnant
  • Currently menstruating or having persistent vaginal discharge
  • Previous hysterectomy
  • Previous diagnosis of cervical cancer

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 2-stage screen
All patients will be enrolled in the two-stage cervical cancer screening protocol
Diagnostic test: 2-stage screen
Pap smear is currently the standard of care for cervical cancer screening in Botswana. In this study, participants will undergo HPV DNA testing at the time of Pap smear collection. If HPV DNA test is positive, they will be referred for colposcopy. Patients who have an HPV negative test but positive Pap smear will be referred for colposcopy per Botswana cervical cancer screening guidelines.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Performance of HPV-Pap screening algorithm
Time Frame: 2 months
Measurement of the sensitivity, specificity and positive predictive value of Pap smear in predicting cervical precancer and cancer in HPV positive, HIV positive women.
2 months
Performance of HPV-VIA screening algorithm
Time Frame: 2 months
Measurement of the sensitivity, specificity and positive predictive value of VIA in predicting cervical precancer and cancer in HPV positive, HIV positive women.
2 months
Performance of HPV-Colposcopy screening algorithm
Time Frame: 6 months
Measurement of the sensitivity, specificity and positive predictive value of Colposcopy in predicting cervical precancer and cancer in HPV positive, HIV positive women.
6 months
Incident and persistent HPV infection at one-year follow-up
Time Frame: 18 months
18 months
Incidence, persistence and progression of histopathologic abnormality at one-year follow-up
Time Frame: 18 months
18 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Beth Israel Deaconess Medical Center

Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

  • Principal Investigator: Rebecca Luckett, MD MPH, Beth Israel Deaconess Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 20, 2018

Primary Completion (Actual)

January 31, 2020

Study Completion (Actual)

January 31, 2020

Study Registration Dates

First Submitted

October 12, 2017

First Submitted That Met QC Criteria

October 26, 2017

First Posted (Actual)

October 27, 2017

Study Record Updates

Last Update Posted (Actual)

May 5, 2020

Last Update Submitted That Met QC Criteria

May 4, 2020

Last Verified

May 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2017P000388
  • 5P30AI060354-14 (U.S. NIH Grant/Contract)

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

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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