Clinical effectiveness and cost-effectiveness of quadrivalent human papillomavirus vaccination in HIV-negative men who have sex with men to prevent recurrent high-grade anal intraepithelial neoplasia

Abstract

We examined the long-term clinical and economic benefits of quadrivalent human papillomavirus (qHPV) vaccine as a secondary/adjunct prevention strategy in the prevention of recurrent high-grade intraepithelial neoplasia (HGAIN) in HIV-negative men who have sex with men (MSM) and are 27 years or older. We constructed a Markov model to evaluate the clinical effectiveness and cost-effectiveness of two strategies: (1) no qHPV vaccine after treatment for HGAIN versus (2) qHPV vaccine after treatment for HGAIN. Model parameters, including natural history of anal cancer, vaccine efficacy measured in terms of hazard ratio (HR) (decrease in the risk of recurrent HGAIN), HGAIN treatment efficacy, utilities, and costs, were obtained from the literature. The outcomes were measured in terms of lifetime risk of anal cancer, lifetime cost, quality-adjusted life years, and incremental cost-effectiveness ratios (ICERs). Sensitivity analysis was conducted on all model parameters. We found that vaccinating HIV-negative MSM reduced the lifetime risk of anal cancer by 60.77% at an ICER of US$87,240 per quality-adjusted life-year. The results were highly sensitive to vaccine efficacy, transition of HGAIN to anal cancer, cost of treatment for HGAIN, vaccine degree of protection over time, and the vaccine duration of protection and less sensitive to HPV clearance, cost of qHPV vaccine, and the transitions from normal to low-grade anal intraepithelial neoplasia (LGAIN) and normal to HGAIN. With an HR of 0.3, the ICER was well below a $50,000 willingness-to-pay threshold; with an HR of 0.5, the ICER was still below a threshold of $100,000. The most critical disease-related factor influencing the cost-effectiveness was the progression of HGAIN to anal cancer. At an annual transition probability below 0.001, the ICER was below $50,000. Vaccinating HIV-negative MSM treated for HGAIN decreases the lifetime risk of anal cancer and is likely to be a cost-effective intervention.

Keywords: Anal neoplasia; Cost-effectiveness analysis; High-grade intraepithelial neoplasia; Human papillomavirus; Quadrivalent human papillomavirus vaccine; Secondary/adjunct prevention.

Figure 1. One-Way Sensitivity Analysis on Vaccine Efficacy

One-way sensitivity analysis shows the impact of vaccine efficacy on the incremental cost-effectiveness ratio (ICER). The vaccine effectiveness is expressed in terms of hazard ratio (HR; i.e., the chance of HGAIN recurrence with vaccination divided by the chance of recurrence without vaccination). The base case efficacy is indicated by an arrow labeled “base case”. As the vaccine efficacy decreases, the ICER increases.

Figure 2. One-way Sensitivity Analysis on Annual Transition Probability of High-Grade Squamous Intraepithelial Lesion to Anal Cancer

One-way sensitivity analysis shows the impact of varying the annual transition probability of high-grade squamous intraepithelial lesion to anal cancer on the incremental cost-effectiveness ratio (ICER). The base case annual transition probability is indicated by an arrow labeled “base case”. With the increases in disease transition probability, the ICER decreases.

Figure 3. Cost-effectiveness Acceptability Curves

The cost-effectiveness acceptability curves show the effect of joint density of all model parameters on the probability of cost-effectiveness. With the increases in the willingness to pay threshold, the probability that the vaccine is cost-effective increases.