Management of precancerous anal intraepithelial lesions in human immunodeficiency virus-positive men who have sex with men: Clinical effectiveness and cost-effectiveness

Abstract

Background: Human immunodeficiency virus (HIV)-positive men who have sex with men (MSM) are at disproportionately high risk for anal cancer. There is no definitive approach to the management of high-grade squamous intraepithelial lesions (HSIL), which are precursors of anal cancer, and evidence suggests that posttreatment adjuvant quadrivalent human papillomavirus (qHPV) vaccination improves HSIL treatment effectiveness. The objectives of this study were to evaluate the optimal HSIL management strategy with respect to clinical effectiveness and cost-effectiveness and to identify the optimal age for initiating HSIL management.

Methods: A decision analytic model of the natural history of anal carcinoma and HSIL management strategies was constructed for HIV-positive MSM who were 27 years old or older. The model was informed by the Surveillance, Epidemiology, and End Results-Medicare database and published studies. Outcomes included the lifetime cost, life expectancy, quality-adjusted life expectancy, cumulative risk of cancer and cancer-related deaths, and cost-effectiveness from a societal perspective.

Results: Active monitoring was the most effective approach in patients 29 years or younger; thereafter, HSIL treatment plus adjuvant qHPV vaccination became most effective. When cost-effectiveness was considered (ie, an incremental cost-effectiveness ratio [ICER] < $100,000/quality-adjusted life-year), do nothing was cost-effective until the age of 38 years, and HSIL treatment plus adjuvant qHPV vaccination was cost-effective beyond the age of 38 years (95% confidence interval, 34-43 years). The ICER decreased as the age at HSIL management increased. Outcomes were sensitive to the rate of HSIL regression or progression and the cost of high-resolution anoscopy and biopsy.

Conclusions: The management of HSIL in HIV-positive MSM who are 38 years old or older with treatment plus adjuvant qHPV vaccination is likely to be cost-effective. The conservative approach of no treatment is likely to be cost-effective in younger patients. Cancer 2017;123:4709-4719. © 2017 American Cancer Society.

Keywords: anal cancer; cost-effectiveness; high-grade squamous intraepithelial lesion; human papillomavirus; human papillomavirus vaccine; management; precursor; treatment.

Figure 1. Percentage cumulative incidence of anal cancer and percentage deaths attributed to anal cancer in 40-year-old MSM

a depicts cumulative risk of anal cancer in a 40-year old male, i.e., considering a base case, for the strategies—(i) do nothing, (ii) active monitoring, (iii) HSIL treatment, and (iv) HSIL treatment plus adjuvant qHPV vaccination—represented in the order of the color intensity from darker to lighter. The outcomes are reported over a period of 10 years and over an average patient’s lifetime. b depicts cumulative risk of death attributed to anal cancer in a 40-year old male, i.e., considering a base case, for the strategies—(i) do nothing, (ii) active monitoring, (iii) HSIL treatment, and (iv) HSIL treatment plus adjuvant qHPV vaccination—represented in the order of the color intensity from darker to lighter. The outcomes are reported over a period of 10 years and over an average patient’s lifetime.

Figure 1. Percentage cumulative incidence of anal cancer and percentage deaths attributed to anal cancer in 40-year-old MSM

a depicts cumulative risk of anal cancer in a 40-year old male, i.e., considering a base case, for the strategies—(i) do nothing, (ii) active monitoring, (iii) HSIL treatment, and (iv) HSIL treatment plus adjuvant qHPV vaccination—represented in the order of the color intensity from darker to lighter. The outcomes are reported over a period of 10 years and over an average patient’s lifetime. b depicts cumulative risk of death attributed to anal cancer in a 40-year old male, i.e., considering a base case, for the strategies—(i) do nothing, (ii) active monitoring, (iii) HSIL treatment, and (iv) HSIL treatment plus adjuvant qHPV vaccination—represented in the order of the color intensity from darker to lighter. The outcomes are reported over a period of 10 years and over an average patient’s lifetime.

Figure 2. Clinical effectiveness by age

a shows quality-adjusted life expectancy by HSIL management strategies and age. The strategies (i) do nothing, (ii) active monitoring, (iii) HSIL treatment, and (iv) HSIL treatment plus adjuvant qHPV vaccination are represented by the lines dotted grey, dashed orange, dotted blue, and dashed red. The QALYs reported using an annual discount rate of 3%. b shows quality-adjusted life expectancy by HSIL management modalities in patients 27–35 years of age (magnified version of Figure 2a). The strategies (i) do nothing, (ii) active monitoring, (iii) HSIL treatment, and (iv) HSIL treatment plus adjuvant qHPV vaccination are represented by the lines dotted grey, dashed orange, dotted blue, and dashed red. The QALYs reported using an annual discount rate of 3%.

Figure 2. Clinical effectiveness by age

a shows quality-adjusted life expectancy by HSIL management strategies and age. The strategies (i) do nothing, (ii) active monitoring, (iii) HSIL treatment, and (iv) HSIL treatment plus adjuvant qHPV vaccination are represented by the lines dotted grey, dashed orange, dotted blue, and dashed red. The QALYs reported using an annual discount rate of 3%. b shows quality-adjusted life expectancy by HSIL management modalities in patients 27–35 years of age (magnified version of Figure 2a). The strategies (i) do nothing, (ii) active monitoring, (iii) HSIL treatment, and (iv) HSIL treatment plus adjuvant qHPV vaccination are represented by the lines dotted grey, dashed orange, dotted blue, and dashed red. The QALYs reported using an annual discount rate of 3%.

Figure 3. One-way sensitivity analysis on age at HSIL diagnosis

Figure shows the incremental cost-effectiveness ratio (95% CI) by HSIL age at diagnosis. The x-axis represents age at HSIL diagnosis and the y-axis represents willingness-to-pay threshold. Willingness-to-pay threshold of $100 000/QALY is considered economically acceptable.

Figure 4. Tornado diagrams displaying the top 15 model parameters in the order of their impact on HSIL age at diagnosis and their impact on ICER

a depicts the top 15 model parameters in the order of their impact on age. The horizontal axis represents the age at HSIL diagnosis. The parameters are arrayed along the vertical line, which represents the minimum HSIL age at diagnosis of 38 years when treatment plus adjuvant qHPV vaccination becomes cost-effective. Bars are arranged in the ascending order of their bar width (degree of uncertainty). The longest bar represents the parameter generating the widest uncertainty. b depicts the top 15 model parameters in the order of their impact on cost-effectiveness. The horizontal axis represents the incremental cost-effectiveness ratio (the ratio of incremental cost and incremental effectiveness comparing undominated strategies). The parameters are arrayed along the vertical line, which represents the outcome point of base case ICER of $73 367/QALY. Bars are arranged in the ascending order of their bar width (degree of uncertainty). The longest bar represents the parameter generating the widest uncertainty. AC, anal cancer; HRA, high-resolution anoscopy

Figure 4. Tornado diagrams displaying the top 15 model parameters in the order of their impact on HSIL age at diagnosis and their impact on ICER

a depicts the top 15 model parameters in the order of their impact on age. The horizontal axis represents the age at HSIL diagnosis. The parameters are arrayed along the vertical line, which represents the minimum HSIL age at diagnosis of 38 years when treatment plus adjuvant qHPV vaccination becomes cost-effective. Bars are arranged in the ascending order of their bar width (degree of uncertainty). The longest bar represents the parameter generating the widest uncertainty. b depicts the top 15 model parameters in the order of their impact on cost-effectiveness. The horizontal axis represents the incremental cost-effectiveness ratio (the ratio of incremental cost and incremental effectiveness comparing undominated strategies). The parameters are arrayed along the vertical line, which represents the outcome point of base case ICER of $73 367/QALY. Bars are arranged in the ascending order of their bar width (degree of uncertainty). The longest bar represents the parameter generating the widest uncertainty. AC, anal cancer; HRA, high-resolution anoscopy