Merkel cell carcinoma and Merkel cell polyomavirus: a systematic review and meta-analysis

Abstract

Several observational studies have assessed the correlation between Merkel cell carcinoma and Merkel cell polyomavirus with variable results. The objective of this systematic review was to determine whether there is a correlation between Merkel cell carcinoma and Merkel cell polyomavirus. Studies assessing the relationship between Merkel cell carcinoma and Merkel cell polyomavirus from January 2008 to August 2014 were pooled from Medline, Embase, PubMed, Cochrane Database of Systemic Reviews and Google Scholar. From each study we collected the first author's last name, publication year, country of origin, type of study design, characteristics of participants, possible variables incorporated into the multivariable analyses and the risk ratio (RR) for Merkel cell carcinoma associated with Merkel cell polyomavirus combined with the corresponding 95% confidence interval (CI). Methodological assessment of the study was evaluated using the Newcastle-Ottawa scale. Crude RR was calculated from the data provided in each article. Meta-analyses for the global RR and for the proportion of positives in both case and control samples were performed. In addition, in order to explore the sources of heterogeneity among the studies, meta-regression and sensitivity analyses are also provided. A total of 22 studies were identified for the analysis. The pooled RR from random-effects analysis was determined to be 6.32 (95% CI, 4.02-9.93). Global proportions of positive samples were 0.79 (95% CI, 0.72-0.84) and 0.12 (95% CI, 0.08-0.19) in the case and control groups, respectively. The findings support the association between Merkel cell carcinoma and Merkel cell polyomavirus. However, a non-negligible percentage of positive results have been identified in controls. Some caution must be taken in the interpretation of these results because heterogeneity between studies was found.

Avelumab in patients with chemotherapy-refractory metastatic Merkel cell carcinoma: a multicentre, single-group, open-label, phase 2 trial

“…Merkel cell polyomavirus is present in approximately 80% of patients with Merkel cell carcinoma, with an incidence as high as 97% in samples assessed with PCR. 2,16,17 The virus integrates into DNA to drive expression of Merkel cell polyomavirus large T antigens, promote tumour proliferation, and disrupt immune responses. 2,18 In virus-negative tumours, a mutational burden signature associated with ultraviolet radiation exposure appears to be important for oncogenesis, leading to increased expression of neoantigens, heightened immunogenicity, and probably an increased requirement for immune evasion by the tumour.…”

The association between geographic location and incidence of Merkel cell carcinoma in comparison to melanoma: An international assessment

“…Immunosuppression by HIV [6], after organ transplantation [7] or due to chronic lymphocytic leukaemia, small lymphocytic lymphoma, or Non-Hodgkin lymphoma (NHL) is considered to be another risk factor for MCC [8]. With the discovery of the Merkel cell polyomavirus (MCPyV) that is present in about 80% of all MCCs in the United States and Europe, a further aetiologic factor of MCC has been established [9]. Notably, MCPyV-negative MCC tumours are characterised by a UV mutational profile [10], whereas MCPyV-positive tumours have a very low UV mutational load.…”

Talimogene laherparepvec for regionally advanced Merkel cell carcinoma: A report of 2 cases

“…Alternatively, these tumors may originate from an immature, totipotent stem cell 5 . Merkel cell polyomavirus (MCPyV), a ubiquitous virus in the human skin microbiome, is a nonenveloped, double-stranded DNA virus directly involved in the pathogenesis of approximately 80% of MCCs 6, 7, 8, 9. Steps involved in the development of MCPyV + tumors include clonal integration into the host cell genome, mutational loss of viral replication competence, expression of 2 key oncoproteins designated small tumor antigen and large tumor antigen, retinoblastoma gene suppression by large tumor antigen, and evasion of a destructive immune response 10, 11.…”