Merkel Cell Carcinoma and Immunosuppression, UV Radiation, and Merkel Cell Polyomavirus

Merkelcell.org Summary

Merkel cell carcinoma (MCC) is a rare type of skin cancer that arises from a combination of factors, including those outlined below. First, immunosuppressive conditions like HIV, organ transplants, and chronic lymphocytic leukemia (CLL) can weaken the immune system, making it harder for the body to fight cancer. Second, UV radiation from the sun can damage DNA and lead to skin cancer. Lastly, the Merkel cell polyomavirus is a common virus that most people get early in life, but in rare cases, it can lead to MCC.

This study analyzed a large number 38,020 MCC cases in the U.S. to estimate how many were linked to these three factors. Because immunosuppressive conditions are rare, only a small percentage of cases were due to these conditions: 0.2% from HIV, 1.5% from organ transplants, and 0.8% from CLL. However, 65% of cases were linked to UVR exposure, and 64% to the Merkel cell polyomavirus. Because multiple factors can contribute to MCC, some cases were linked to both UVR and the virus. These findings suggest that most MCC cases in the U.S. are caused by UVR exposure or the Merkel cell polyomavirus, with only a small percentage linked to immunosuppression. Efforts to lower the number of MCC cases in the U.S. could focus on limiting UVR exposure and education on immunosuppressive risk factors.

Abstract

Importance: Merkel cell carcinoma (MCC) is a rare but aggressive skin cancer. Quantifying the contribution of major potentially modifiable risk factors to the burden of MCC may inform prevention efforts.

Objective: To estimate the population attributable fraction of MCC cases in the US that were attributable to major immunosuppressing conditions (eg, HIV, solid organ transplant, chronic lymphocytic leukemia [CLL]), ambient UV radiation [UVR] exposure, and Merkel cell polyomavirus [MCPyV]).

Design, setting, and participants: This epidemiological assessment combined data from population-based registries and case series and included cases of MCC that were diagnosed from January 2001 to December 2019 diagnosed in people with HIV, solid organ transplant recipients, and patients with CLL who were identified through population-based cancer registries and linkages with HIV and transplant registries. UVR-based on cloud-adjusted daily ambient UVR irradiance was merged with cancer registry data on the county of residence at diagnosis. Studies reporting the prevalence of MCPyV in MCC specimens collected in the US were combined via a meta-analysis.

Exposures: HIV, solid organ transplant, CLL, UVR, and MCPyV.

Main outcomes and measures: Population attributable fraction of MCC cases attributable to major risk factors.

Results: A total of 38 020 MCCs were diagnosed in the US among xx patients (14 325 [38%] female individuals; 1586 [4%] Hispanic, 561 [1%] non-Hispanic Black, and 35 171 [93%] non-Hispanic White individuals). Compared with the general US population, MCC incidence was elevated among people with HIV (standardized incidence ratio [SIR], 2.78), organ transplant recipients (SIR, 13.1), and patients with CLL (SIR, 5.75). Due to the rarity of these conditions, only 0.2% (95% CI, 0.1%-0.3%) of MCC cases were attributable to HIV, 1.5% (95% CI, 1.4%-1.7%) to solid organ transplant, and 0.8% (95% CI, 0.5%-1.3%) to CLL. Compared with individuals of racial and ethnic minority groups, MCC incidence was elevated among non-Hispanic White individuals at lower and higher ambient UVR exposure levels (incidence rate ratios: 4.05 and 4.91, respectively, for MCC on the head and neck). Overall, 65.1% (95% CI, 63.6%-66.7%) of MCCs were attributable to UVR. Based on a meta-analysis of 19 case series, 63.8% (95% CI, 54.5%-70.9%) of MCCs were attributable to MCPyV. Studies were identified from a MEDLINE search performed on October 12, 2023.

Conclusions and relevance: The results of this study suggest that most MCC cases in the US were attributable to ambient UVR exposure or MCPyV, with a small fraction due to immunosuppressive conditions. Efforts to lower MCC incidence could focus on limiting UVR exposure.