SCREENING HIGH-RISK MEN FOR ANAL CARCINOGENSIS: MODEL DEVELOPMENT AND POLICY ANALYSIS

Purpose: Standardized screening protocols for anal cancer do not yet exist despite the growing evidence that this human papillomavirus (HPV)-related cancer is preceded by premalignant stages, which if detected and removed, may prevent progression to cancer. Men who have sex with men (MSM) who are human immunodeficiency virus (HIV)-infected are among those at highest risk for anal cancer development. In order to inform policy recommendations in the United States, we estimated the health benefits and resource trade-offs associated with alternative primary anal cancer screening strategies for HIV-infected MSM.  

Method: We developed and calibrated a natural history microsimulation model that reflects the most recent understanding of anal carcinogenesis, accounting for interactions between HPV type-specific infections, CD4 lymphocyte strata, and anti-retroviral treatment (ART) status. Relevant strategies involved cytology-based screening, which varied by screening interval (i.e., every 1-3 years) and age at which men initiate screening (i.e., 30 vs. 40 years). Triage of abnormal results involved high-resolution anoscopy. Primary outcomes included discounted life expectancy (3% per year), cancer risk reduction and resource use (number of anoscopies performed). We calculated the incremental harm-benefit ratio (IHBR) in terms of the additional number of anoscopies required per year of life saved (YLS) for each strategy compared with the next most harmful strategy. Sensitivity analyses were conducted on test characteristics, and parameter uncertainty for progression to invasive cancer.

Results: Compared with no screening, the least intensive strategy is projected to reduce cancer risk by 24%, while the most intensive strategy may reduce cancer risk by 66% among HIV-infected MSM. All strategies that initiated screening at age 40 were dominated by strategies that started at age 30. For those strategies on the harm-benefit frontier, triennial cytology-based screening required an additional 7.2 anoscopies per YLS compared with no screening, while the most intensive screening strategy (annual) required an additional 40.3 anoscopies per YLS, compared with biennial screening. The rank-order of strategies was preserved when we assumed a less sensitive anal cytology test. 

Conclusion: For HIV-infected MSM, the most efficient anal cancer screening strategies involve starting at age 30; however, the optimal screening interval is unclear, as more intensive strategies require explicit trade-offs between the harms and benefits, and depend on capacity constraints and society's willingness-to-pay for life-years and other health benefits.