Antibody Response to Merkel Cell Polyomavirus Associated with Incident Lymphoma in the Epilymph Case–Control Study in Spain

Abstract

Background: Merkel cell polyomavirus (MCV) has been identified as the cause of Merkel cell carcinoma. The increased incidence of chronic lymphocytic leukemia in Merkel cell cancer cohorts and the lymphotropic properties of the virus suggest a possible viral association with lymphomagenesis. To investigate this potential role, we explored seroreactivity against MCV VP1 capsids within the Epilymph case-control study in Spain.Methods: Serum samples from 468 incident lymphomas, categorized into up to 11 entities, and 522 controls frequency matched by age, sex, and recruitment center were tested for MCV antibodies by enzyme immunoassay using Virus-Like-Particles. Adjusted multinomial logistic regression was used to estimate the OR and 95% confidence interval (CI) associated to MCV seroprevalence. Immunosuppressed subjects were excluded.Results: MCV seroprevalence was 82% in controls and 85% in lymphoma cases. Among 11 lymphoma categories, MCV seropositivity was significantly higher in diffuse large B-cell lymphomas (DLBCL; 96.4%; OR ¼ 6.1, 95%CI ¼ 1.9-19.8), as compared with controls. MCV prevalences were also higher in follicular lymphoma, lymphoplasmacytic lymphoma, chronic lymphocytic leukemia, Hodgkin lymphoma, and mature T-cell lymphoma but differences did not reach statistical significance. Lower prevalences were observed for multiple myeloma and other B-cell lymphoma. Exclusion of samples collected after start of treatment did not change the results. In a subset analysis, no significant association was observed between BKV and JCV seroprevalence and DLBCL.Conclusion: The association observed between serologic evidence of MCV exposure and DLBCL warrants further research. Impact: MCV might be involved in the pathway of DLBCL and other lymphomas. Cancer Epidemiol Biomarkers Prev; 21(9); 1592-8. Ó2012 AACR.

Seroreactivity against Merkel cell polyomavirus and other polyomaviruses in chronic lymphocytic leukaemia, the MCC-Spain study

“…Differences from our previous results in MCPyV seroprevalence (Robles et al, 2012), in which we observed an increased seroprevalence, might be explained by control selection, due to the previous use of hospital controls versus the current use of general population ones. The decreased seroprevalences against all polyomaviruses in our CLL subjects is somehow consistent with the findings from Teras et al (2014), in which none of the polyomaviruses showed a significant association with CLL, but half of them showed a decreased risk of CLL among seroprevalent subjects.…”

“…However, the presence of a truncated LT-Ag MCPyV sequence in the nucleus, a peculiarity of MCPyV in Merkel cell carcinoma cells, has been reported in highly purified CD19 + /CD5 + CLL cells (Haugg et al, 2011;Pantulu et al, 2010). Serology data are furthermore inconsistent; in a previous case-control study we identified an increased MCPyV seroprevalence in CLL patients (Robles et al, 2012) whereas in a recent paper a decreased risk was observed (Teras et al, 2015), although none of them significant. The latter paper also observed null associations for seven additional polyomaviruses and subsequent risk of CLL, although potential concerns in sample size were raised.…”

Bladder cancer and seroreactivity to BK, JC and Merkel cell polyomaviruses: The Spanish bladder cancer study

“…Finally, the high seroreactivity could also be related to a viral reactivation in temporal proximity to cancer development; the latter happening before and maybe contributing to bladder cancer pathogenesis or happening later as a result of an immune system impairment after the disease onset. The higher seroreactivity observed for not only one but two viruses, as well as our previous observation of a higher seroprevalence in lymphomas, could indicate reverse causality (high seroreactivity as a consequence of immune impairment) rather than a causative role. However, other viruses such as EBV or HPV are able to cause more than one cancer depending on the body location and geographic area.…”

Prediagnostic Circulating Polyomavirus Antibody Levels and Risk of Non-Hodgkin Lymphoma

“…A recent International Agency for Research on Cancer panel classified Merkel cell polyomavirus (MCV) as a probable carcinogen and BK and JC polyomaviruses (BKV, JCV) as possible carcinogens (1). In the only three epidemiologic studies (2)(3)(4) to examine associations of BKV and JCV antibodies with risk of non-Hodgkin lymphoma (NHL) or NHL subtypes, no associations were found for BKV, but for JCV results were inconsistent. The only study to examine MCV and risk of NHL showed positive associations with some NHL subtypes (4).…”

“…In the only three epidemiologic studies (2)(3)(4) to examine associations of BKV and JCV antibodies with risk of non-Hodgkin lymphoma (NHL) or NHL subtypes, no associations were found for BKV, but for JCV results were inconsistent. The only study to examine MCV and risk of NHL showed positive associations with some NHL subtypes (4). Because of the limited number of studies to date, we examined associations of plasma antibody levels of JCV, BKV, and MCV-as well as several other polyomaviruses [WU polyomavirus (WUV); KI polyomavirus (KIV); human polyomavirus 6 (HPy6); human polyomavirus 7 (HPy7); Trichodysplasia spinulosa-associated polyomavirus (TSV)]-with risk of NHL in the American Cancer Society (ACS) Cancer Prevention Study-II (CPS-II) Nutrition Cohort, a large prospective study of U.S. men and women.…”