2-stage Cervical Cancer Screening in Botswana
2-stage Cervical Cancer Screening in 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.
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.
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