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. CON-CLUSIONS: 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;123:4709-19.

Adjuvant HPV vaccination for anal cancer prevention in HIV-positive men who have sex with men: The time is now

“…Model accuracy was established as the cumulative risks predicted by the model were within the 95% confidence interval of the cumulative risks reported in the literature. Detailed model validation is presented in Supplementary Appendix 3 and elsewhere [19, 28]. …”

“…Previous studies evaluated the effectiveness or cost-effectiveness of adjuvant HPV vaccination compared to HSIL treatment alone (i.e., adding HPV vaccination to HSIL treatment regimen) [14, 15, 47] or determined the cost-effectiveness of HSIL management [19] or surveillance after HSIL treatment [48]. No guidelines exist for anal HSIL management and given the uncertainty associated with the efficacy of HSIL treatment and adjuvant HPV vaccination, in the present study, we first comprehensively compared the outcomes of all potential HSIL management options and then conducted value-of-information analysis to determine the value of future research needed to resolve all possible uncertainty among HIV-infected MSM.…”

“…To conduct VOI analysis, we used a previously developed and validated state-transition model that simulated the natural history of anal carcinoma in HIV-infected MSM and followed patients after treatment for initial HSIL for any risk of subsequent recurrence or potential cancer [19, 28] (Appendix S1.1). The model compared four strategies: do nothing, active monitoring (using annual digital anorectal examination (DARE) and high resolution anoscopy (HRA)), treatment for HSIL (using ablation), and treatment plus adjuvant qHPV vaccination [16] (Appendix S1.2).…”

“…In addition to these, the model included health states for HIV progression based on the patient’s CD4 count (i.e., CD4 >500 cells/mm 3 , CD4 between 200–500 cells/mm 3 , and CD4 <200 cells/mm 3 ). Patient CD4 count, rates of HSIL progression or regression, and natural history post initial regression were obtained from the literature or calibrated using a separate natural history model for anal carcinogenesis (Appendix S1.3; Appendix Table T1.1 and T1.2) [2, 9, 19, 29–31]. Our model also considered the possibility of receiving antiretroviral therapy (ART) and the impact of change in CD4 count on anal carcinogenesis.…”

“…Although clinical trials found no evidence on efficacy of HPV vaccination for prevention of anal persistent HPV infection [18], no empirical trial data exist regarding the effectiveness of adjuvant vaccination for prevention of recurrent anal HSIL or anal cancer in HIV-infected individuals. Considering this uncertainty, a modeling based analysis showed that “treatment plus vaccination” could be a cost-effective HSIL management strategy even under the assumption of worst-case efficacy of reducing HSIL recurrence for only up to 2 years [19]. Therefore, the questions then arise: Should the guidelines consider implementing post-treatment adjuvant qHPV vaccination despite the lack of direct evidence from empirical studies?…”