Long-Term Outcomes of Adding HPV Vaccine to the Anal Intraepithelial Neoplasia Treatment Regimen in HIV-Positive Men Who Have Sex With Men

Abstract

Background: Recent evidence shows that quadrivalent human papillomavirus (qHPV) vaccination in men who have sex with men (MSM) who have a history of high-grade anal intraepithelial neoplasia (HGAIN) was associated with a 50% reduction in the risk of recurrent HGAIN. We evaluated the long-term clinical and economic outcomes of adding the qHPV vaccine to the treatment regimen for HGAIN in human immunodeficiency virus (HIV)-positive MSM aged ≥27 years.

Methods: We constructed a Markov model based on anal histology in HIV-positive MSM comparing qHPV vaccination with no vaccination after treatment for HGAIN, the current practice. The model parameters, including baseline prevalence, disease transitions, costs, and utilities, were either obtained from the literature or calibrated using a natural history model of anal carcinogenesis. The model outputs included lifetime costs, quality-adjusted life years, and lifetime risk of developing anal cancer. We estimated the incremental cost-effectiveness ratio of qHPV vaccination compared to no qHPV vaccination and decrease in lifetime risk of anal cancer. We also conducted deterministic and probabilistic sensitivity analyses to evaluate the robustness of the results.

Results: Use of qHPV vaccination after treatment for HGAIN decreased the lifetime risk of anal cancer by 63% compared with no vaccination. The qHPV vaccination strategy was cost saving; it decreased lifetime costs by $419 and increased quality-adjusted life years by 0.16. Results were robust to the sensitivity analysis.

Conclusions: Vaccinating HIV-positive MSM aged ≥27 years with qHPV vaccine after treatment for HGAIN is a cost-saving strategy. Therefore, expansion of current vaccination guidelines to include this population should be a high priority.

Keywords: anal neoplasia; cost-effectiveness analysis; human papillomavirus; quadrivalent human papillomavirus vaccine; secondary/adjunct prevention.

Figure 1.

Schematic model depicting health states of clinical and economic significance. At any given time, a patient occupies one of the health states represented by ovals. Arrows between states represent possible transitions based on annual probabilities. Dashed rectangles distinguish anal histology states by CD4 cell count (cells/mm³). As time progresses, patients can transition to other states and acquire cost and health utilities associated with that state. Anal histology and high-grade anal intraepithelial neoplasia (HGAIN) treatment characteristics were overlaid on the human immunodeficiency virus (HIV) status of the patients; that is, anal disease and HIV disease could concurrently progress or regress with time. The model stops when all patients transition to the death state. Note that a patient could transition to the death state from any of the above states because of background mortality (for the sake of clarity, these transitions are not shown in the figure). Abbreviations: HGAIN, high-grade anal intraepithelial neoplasia; HPV, human papillomavirus; LGAIN, low-grade anal intraepithelial neoplasia.

Figure 2.

Model-predicted incidence rate of anal cancer per 100 000 person-years with and without quadrivalent human papillomavirus (qHPV) vaccination. The model-predicted incidence of anal cancer is shown under the scenario of (1) no vaccination, (2) a vaccination strategy that assumes a constant degree of protection throughout the duration of protection, (3) vaccination under the assumption that the decrease in degree of protection follows a normal distribution, and (4) vaccination under the assumption that the decrease in degree of protection follows an exponential distribution. We used a constant waning rate of 1/30 per year to predict the decline in degree of protection that follows a normal distribution and a mean and standard deviation of 30 and 5 years, respectively, to predict the decline that follows an exponential distribution.

Figure 3.

A, Tornado diagram displaying the 20 model parameters with the impact on cost-effectiveness in the order of sensitivity. Cost saving means that vaccination decreased lifetime cost and increased quality-adjusted life expectancy; cost-effective means that vaccination increased both lifetime cost and quality-adjusted life expectancy; however, the incremental cost-effectiveness ratio (ICER) was below the societal willingness-to-pay threshold of $50 000/quality-adjusted life year (QALY). The horizontal axis represents outcome in terms of ICER (additional cost of including a vaccination program to gain an additional QALY). Parameters are arrayed along the vertical solid line, which represents the outcome point of base-case ICER. Bars are arranged in descending order of bar width, which represents the degree of uncertainty (longest bar represents parameter generating widest uncertainty). We divided the horizontal axis into 3 regions: regions of cost saving, cost-effectiveness, and cost-ineffectiveness. CD4 represent CD4 cell count (cells/mm³). B, Cost-effectiveness acceptability curves comparing no qHPV vaccination with qHPV vaccination strategy. This plot shows the probability that the vaccination strategy is cost-effective compared with the no-vaccination strategy and the no-vaccination strategy is cost-effective compared with the vaccination strategy for a range of willingness-to-pay thresholds that a decision maker may consider acceptable. Abbreviations: HGAIN, high-grade anal intraepithelial neoplasia; HIV, human immunodeficiency virus; HR, hazard ratio; qHPV, quadrivalent human papillomavirus vaccine.