ABSTRACT
Primary high-risk human papillomavirus (HPV) testing has become first line screening for cervical cancer in
high-income countries. The feasibility of this approach in low- and middle-income countries is less clear, as is
the role of primary HPV screening among women living with human immunodeficiency virus (HIV). Evaluating
the performance of cervical cancer screening algorithms using primary HPV testing in high HIV prevalence
settings like Botswana is essential for establishing an evidence-based strategy for cervical cancer screening in
populations with a high burden of HIV living in low- and middle-income countries. The proposed study
evaluates innovative HPV-based cervical cancer screening algorithms in women living with HIV (WLHIV) and
builds a longitudinal cohort to evaluate long-term outcomes. With internal departmental funding, I have begun
recruitment of a cohort of 3,000 women, 50% of whom are living with HIV, in South East District, Botswana.
Participants in this cohort undergo baseline cervical cancer screening with high-risk HPV testing and 3 types of
visual triage evaluation: 1) visual assessment with acetic acid, 2) colposcopy, and 3) automated visual
evaluation. Biopsy with histopathology is collected as the gold standard in comparing the efficacy of these
HPV-based screening algorithms. Excisional treatment is offered as indicated by colposcopy and biopsy
results. Aim 1 of the proposed K08 will evaluate the performance of these HPV-based screening algorithms, as
well as HPV testing alone in detecting cervical dysplasia in WLHIV. Additionally, in Aim 2, I will conduct interval
HPV-based cervical cancer screening for the WLHIV in this cohort to evaluate safe and effective screening
intervals. Specifically, I will repeat HPV testing at 2 years in WLHIV who tested positive for HPV and had
benign pathology at baseline, and at 3 years in WLHIV who tested negative for HPV at baseline. Women will
undergo triage testing according to the findings of the baseline screening study. Based on the data from
baseline and interval screening, in Aim 3, I will develop a pilot implementation study to evaluate the
incorporation of HPV-based cervical cancer screening into routine health services, in collaboration with the
Ministry of Health and Wellness of Botswana. This K08 will provide protected research time and build skills in
advanced clinical data analytics, clinical trial design, and implementation science to become an independent
NIH-funded researcher. My career goal is to improve the health and wellness of women through evaluation and
implementation of high-performance cervical cancer screening that is within reach of all women regardless of
their geography and socioeconomic status. The research will be conducted with the support of the Beth Israel
Deaconess Medical Center and through the Botswana Harvard AIDS Institute Partnership with which the PI
has a long-standing research appointment. Furthermore, this research will be done in collaboration with the
Ministry of Health and Wellness of Botswana, thus impacting national cervical cancer screening policy as well
as international policy for WLHIV.
