Comparative Assessment of p16/Ki-67 Dual Staining Technology for Cervical Cancer Screening in Women Living with HIV (COMPASS-DUST) – Study Protocol

Abstract

AbstractThe risk of progression of low-grade (CIN1) to high-grade cervical intraepithelial neoplasia (CIN2/3) is 3–5 times higher for women living with HIV (WLHIV) than for HIV-negative women. Evidence suggests that the current cervical cancer screening methods perform less effectively in WLHIV. Molecular-based p16/Ki-67 dual staining technology (DUST) is a safe and rapid assay that could be used to detect CIN2/3 with higher sensitivity and specificity. The study in this protocol will evaluate the performance of p16/Ki-67 dual staining technology (DUST) in cervical cancer screening among WLHIV. We will conduct an intra-participant comparative study (Phase 1) to enrol n=1,123 sexually active WLHIV aged 25–65 years at two accredited adult HIV treatment centres in Lagos, Nigeria to compare the performance of DUST to the currently used screening methods (Pap smear, hr-HPV DNA, or VIA testing) in detecting high-grade CIN and cancer (CIN2+). Subsequently, a prospective cohort study (Phase 2) will be conducted by enrolling all the WLHIV who are diagnosed as having low-grade CIN (CIN1) inPhase 1for a 6-monthly follow-up for 2 years to detect the persistence and progression of CIN1 to CIN2+. The findings of this study may provide evidence of the existence of a better performance screening method for the primary and triage detection of CIN2+ in WLHIV. It may also demonstrate that this high-performance test can improve the long-term predictive accuracy of screening by extending the intervals between evaluations and thus decrease the overall cost and increase screening uptake and follow-up compliance in WLHIV.Author SummaryAs there is evidence to suggest that the currently used screening methods for cervical cancer are less effective in women living with HIV (WLHIV), the proposed study in this protocol will evaluate the performance of a molecular-based p16/Ki-67 dual staining technology (DUST) in the primary and HPV-triage detection of CIN2+ in WLHIV. Using an intra-participant comparative study design (Phase 1), n=1,123 sexually active WLHIV aged 25–65 years will be enrolled at two accredited adult HIV treatment centres in Lagos, Nigeria to compare the performance of DUST to the currently used screening methods (Pap smear, hr-HPV DNA, or VIA testing) in detecting CIN2+. InPhase 2, a prospective cohort study design will be used to enrol all WLHIV who are diagnosed as having CIN1 inPhase 1for a 6-monthly follow-up for 2 years to detect persistent CIN1 and progression of CIN1 to CIN2/3. Overall, this very promising molecular-based technology (DUST) could reduce the long-term cumulative screening cost and procedure-related anxiety and fear, and subsequent improvement in cervical cancer screening uptake and follow-up compliance in WLHIV. We anticipate that these will have significant public health impacts as this innovative method will offer a unique paradigm shift for future control of cervical cancer within an integrated HIV treatment setting in LMICs.