Identifying Optimal Cervical Cancer Prevention Strategies for HIV-positive Women in Senegal, West Africa – Quantification of the Natural History of HPV Among HIV-positive Women and Markov Cohort Cost-Effectiveness Analyses

Abstract

Objective. The interaction between human immunodeficiency virus (HIV) and human papillomavirus (HPV) results in an increased burden of cervical cancer among HIV-positive women. This research aims to shed light on the important topic of HIV/HPV co-infection with the goal of informing HPV disease prevention efforts. Specifically, using longitudinal data we estimated the natural history of HPV and cervical cancer among HIV-positive women to inform cost-effectiveness modeling aimed at identifying optimal targeted prevention approaches for this high-risk population. Methods. In total 1,277 women (45% positive for HIV-1 and/or HIV-2) were followed for an average of two years in Senegal, West Africa between 1994 and 2010. Cytology and HPV DNA testing were performed at approximately 4-month intervals. Competing risk modeling was used to estimate rates for transitioning between three clinical relevant natural history stages (Normal, HPV, and HSIL) for HIV-positive and HIV-negative women separately. Markov cohort modeling was used to simulate the impact of various cervical cancer screening strategies among HIV-positive women. Specifically, we compared the relative cost-effectiveness of six screening strategies (Hybrid Capture 2 HPV testing, rapid HPV testing, cytology, visual inspection with acetic acid (VIA), HPV testing followed by cytology triage, and HPV testing followed by VIA triage) and five screening frequencies using projected life expectancy and incremental cost-effectiveness ratios (ICER). Further, the potential cost-effectiveness of HPV vaccination at the time of HIV diagnosis was simulated under various theoretical effectiveness scenarios. One-way and probabilistic sensitivity analyses were conducted to explore the impact of uncertainty on results. Results. HIV-positive women had significantly higher rates of progression and lower rates of regression compared to HIV-negative women (i.e. adverse transitions). Among those with HIV infection with multiple HPV types, HPV-16/18, HIV-1, and CD4+ count <200 were associated with adverse transitions. Across a broad range of screening scenarios, VIA was identified as the most cost-effective and contextually feasible screening approach. Compared to no screening, annual VIA resulted in an average discounted increased life expectancy of 1.7 months and a 40% reduction in cervical cancer incidence with an ICER of I$1,500 per life year saved. High underlying HPV prevalence among HIV-positive women significantly reduced the cost-effectiveness of HPV testing. HPV vaccination was only cost-effective under optimal vaccine efficacy and/or costing scenarios. Specifically, with costs ≥I$31 vaccination became dominated when vaccine efficacy fell below approximately 70% and 40% for reducing transitions from Normal to HPV-16/18 and HPV-Other states, respectively. Conclusions. High rates of adverse transitions indicate that targeted screening for the growing population of HIV-positive women in Africa is needed. Based on World Health Organization criterion for cost-effectiveness, targeted VIA screening represents an important prevention opportunity among this high-risk population. With lower vaccine-induced titer levels reported among adult HIV-positive women and a potential corresponding reduction in vaccine efficacy, HPV vaccination costs must be reduced for primary prevention to be cost-effective in comparison to screening. Efforts to implement targeted screening, reduce vaccine costs, develop therapeutic vaccines, and evaluate upcoming HPV antiviral treatments should be made.