ClinicalTrials.gov
ClinicalTrials.gov Menu

2-stage Cervical Cancer Screening in Botswana

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03324009
Recruitment Status : Recruiting
First Posted : October 27, 2017
Last Update Posted : August 22, 2018
Sponsor:
Collaborator:
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party):
Rebecca Luckett, Beth Israel Deaconess Medical Center

Brief Summary:
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 HIV-positive women in Botswana using hrHPV testing. The two protocols include hrHPV testing followed by Pap Smear evaluation and hrHPV testing followed by VIA. The evidence generated will be critical to guiding cervical cancer screening in HIV-infected women across resource settings.

Condition or disease Intervention/treatment Phase
Cervical Cancer HIV/AIDS Diagnostic Test: 2-stage screen Not Applicable

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 sensitivity, specificity, and positive predictive value (PPV) of two different two-stage cervical cancer screening algorithms for HIV-positive women in Botswana: HPV followed by Papanicolaou (Pap) smear, and HPV followed by visual inspection with acetic acid (VIA). The specific aims are:

  1. To determine the sensitivity, specificity, and PPV of a two-stage screening algorithm that utilizes HPV testing followed by Pap smear for the detection of high-grade cervical dysplasia, using colposcopy with histology as the gold standard.
  2. To determine the sensitivity, specificity, and PPV of a two-stage screening algorithm that utilizes HPV testing followed by VIA for the detection of high-grade cervical dysplasia, using colposcopy with histology as the gold standard.

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 the commercially-available Roche Cobas® HPV Assay. 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 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 both HPV/Pap and HPV/VIA two-stage algorithms while providing the highest-quality follow-up to cervical cancer screening abnormalities in Botswana.

Participants will thus have a total of two study-related encounters if they are HPV positive—one for initial HPV and Pap specimen collection and then one for VIA and colposcopy. Participants who are HPV negative and Pap smear negative will only have the one study-related initial screening visit. Participants who are HPV negative and Pap smear positive will be referred to colposcopy per Botswana cervical cancer screening protocol.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 300 participants
Intervention Model: Single Group Assignment
Intervention Model Description: Cross-sectional study
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Development of a Two-stage Cervical Cancer Screening Algorithm for Botswana
Actual Study Start Date : April 20, 2018
Actual Primary Completion Date : August 3, 2018
Estimated Study Completion Date : December 2018

Resource links provided by the National Library of Medicine


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.




Primary Outcome Measures :
  1. 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. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   25 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03324009


Contacts
Contact: Rebecca Luckett, MD MPH +267 7433 3773 rluckett@aphmfp.org
Contact: Katharine Esselen, MD MBA 1-617-939-6406 kesselen@bidmc.harvard.edu

Locations
Botswana
Princess Marina Hospital Recruiting
Gaborone, Botswana
Contact: Gladness Tlhomelang    +2673973776      
Sponsors and Collaborators
Beth Israel Deaconess Medical Center
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
Principal Investigator: Rebecca Luckett, MD MPH Beth Israel Deaconess Medical Center
  Study Documents (Full-Text)

Documents provided by Rebecca Luckett, Beth Israel Deaconess Medical Center:
Informed Consent Form  [PDF] August 8, 2017


Additional Information:
Publications:
de Sanjose S, Quint WG, Alemany L, Geraets DT, Klaustermeier JE, Lloveras B, Tous S, Felix A, Bravo LE, Shin HR, Vallejos CS, de Ruiz PA, Lima MA, Guimera N, Clavero O, Alejo M, Llombart-Bosch A, Cheng-Yang C, Tatti SA, Kasamatsu E, Iljazovic E, Odida M, Prado R, Seoud M, Grce M, Usubutun A, Jain A, Suarez GA, Lombardi LE, Banjo A, Menéndez C, Domingo EJ, Velasco J, Nessa A, Chichareon SC, Qiao YL, Lerma E, Garland SM, Sasagawa T, Ferrera A, Hammouda D, Mariani L, Pelayo A, Steiner I, Oliva E, Meijer CJ, Al-Jassar WF, Cruz E, Wright TC, Puras A, Llave CL, Tzardi M, Agorastos T, Garcia-Barriola V, Clavel C, Ordi J, Andújar M, Castellsagué X, Sánchez GI, Nowakowski AM, Bornstein J, Muñoz N, Bosch FX; Retrospective International Survey and HPV Time Trends Study Group. Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study. Lancet Oncol. 2010 Nov;11(11):1048-56. doi: 10.1016/S1470-2045(10)70230-8. Epub 2010 Oct 15.

Responsible Party: Rebecca Luckett, Instructor in Obstetrics, Gynecology and Reproductive Biology, Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier: NCT03324009     History of Changes
Other Study ID Numbers: 2017P000388
5P30AI060354-14 ( U.S. NIH Grant/Contract )
First Posted: October 27, 2017    Key Record Dates
Last Update Posted: August 22, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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

Additional relevant MeSH terms:
Uterine Cervical Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Uterine Cervical Diseases
Uterine Diseases
Genital Diseases, Female