Abstract 843: The burden of Merkel cell carcinoma attributable to immunosuppression, ultraviolet radiation, and Merkel cell polyomavirus in the United States

Abstract Background: Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer. No published study has estimated the contribution of the major potentially modifiable risk factors, such as immunosuppression, ultraviolet radiation (UVR) and infection with Merkel cell polyomavirus (MCPyV), to the burden of MCC in the US. We estimated the population attributable fractions (PAFs) for MCC associated with immunosuppression (HIV and organ transplantation), MCPyV, and UVR in the US during 2001-2020. Methods: We calculated PAFs for immunosuppression and UVR using the formula: prevalence in cases (Pc)*[(Relative risk, RR-1)/RR]. The proportion of MCC cases among organ recipients and people with HIV (Pc) were derived from US cancer registries in the HIV/AIDS Cancer Match Study, Transplant Cancer Match Study, and the Surveillance Epidemiology and End Results (SEER) Program data. To approximate the RRs, we calculated standardized incidence ratios (SIRs) comparing MCC incidence in people with HIV and organ recipients to the general population. We merged SEER data on MCC cases by county with data on ambient UVR levels in order to create population quintiles of UVR exposure. Since only non-Hispanic White individuals showed elevated IRRs for increased ambient UVR exposure, we estimated the PAF of UVR by calculating incidence rate ratios (IRR ≈ RR) comparing MCC incidence in non-Hispanic White individuals to all other races/ethnicities (at any UVR level) as the reference; here, Pc was the proportion of non-Hispanic White patients in each quintile. To estimate the PAF of MCPyV, we meta-analyzed US studies reporting on MCPyV prevalence in MCC tissues (here PAF ≈ Pc). Results: Over the study period (2001-2020), 40,571 MCCs were diagnosed in the US. Compared to the general population, organ recipients had 13 times higher (SIR=12.7, CI: 11.3-14.2) and people with HIV had three times higher (SIR=2.78, CI: 2.01-3.75) risk of MCC. Due to the rarity of these exposures (HIV Pc = 0.4%; Transplant Pc = 1.9%), only 0.2% of MCC cases were attributable to HIV and 1.7% were attributable to organ transplantation. Compared with people in other racial/ethnic groups, the IRRs of non-Hispanic White individuals at the various levels of ambient UVR for MCC arising on the head and neck ranged from 4.24 to 5.03 and for other primary sites ranged from 2.81 to 3.36. After combining the PAFs for these sites, the overall PAF for UVR was 65.8%. Meta-analyzing 20 studies with 984 MCC cases combined, we found that 66.1% (CI: 58.0-72.2%) of MCCs were attributable to MCPyV. Conclusions: While a small proportion of MCCs were due to immunosuppression from HIV infection and organ transplantation, UVR and MCPyV played a major role in MCC burden. Future research is required to assess the combined impact of these risk factors on MCC incidence. Citation Format: Jacob T. Tribble, Karena Volesky-Avellaneda, Qianlai Luo, Michael R. Sargen, Isaac Brownell, Elizabeth K. Cahoon, Meredith Shiels, Ruth Pfeiffer, Adrianne Moreno, Brenda Y. Hernandez, Eric Engels. The burden of Merkel cell carcinoma attributable to immunosuppression, ultraviolet radiation, and Merkel cell polyomavirus in the United States [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 843.