Role of human polyomaviruses in lymphoproliferative disorders and bladder cancer

Abstract

Polyomaviruses are suspected to cause cancer in humans although to date Merkel cell polyomavirus (MCPyV) is the only proven human carcinogen. Potential associations of up to nine polyomaviruses with 468 lymphoproliferative disorders, 1135 bladder cancer and 359 chronic lymphocytic leukemia (CLL) subjects using three case-control studies in Spain has been explored. Viral exposure was measured as seroreactivity against these viruses by virus-like-particles enzyme linked immunosorbent assay and fluorescent bead-based multiplex serology technology. In explored lymphomas, only diffuse large b-cell lymphoma (DLBCL) showed a significant six-times higher MCPyV seroprevalence (OR=6.10; 95%CI=1.88-19.75) than controls. Bladder cancer cases showed significant higher seroreactivities against BKPyV (OR= 1.37; 95%CI=1.04-1.80) and MCPyV (OR=1.48; 95%CI=1.16-1.88). In CLL, lower seroprevalences for the nine polyomaviruses tested were obtained (OR range=0.21-0.70). The serological patterns obtained in DLBCL and bladder cancer cannot exclude reactive patterns due to disease. Confirmation by means of prospective and molecular studies is required to adequately interpret the associations obtained. Our results in CLL are inconclusive for carcinogenesis due to strong lower seroreactivities. It is unlikely the polyomaviruses explored could play a role in CLL.

Es sospita que els Polyomaviruses causen càncer en humans però només el poliomavirus de cèl•lules de Merkel (MCPyV) es carcinògen humà confirmat. Fins a nou poliomavirus en 468 trastorns limfoproliferatius, 1135 càncers de bufeta i 359 leucèmies limfocítica crònica (LLC) s’han explorat mitjançant tres estudis cas-control a Espanya. L’exposició viral es va mesurar mitjançant enzyme linked immunosorbent assay amb virus-like-particles i tecnologia múltiplex de serologia fluorescent basada en beads. Dels limfomes explorats, nomes el limfoma difús de cèl•lules b grans (LDCBG) va mostrar una MCPyV seroprevalença significativament 6-cops mes alta (OR=6.10; 95%CI=1.88-19.75) versus controls. Els casos de càncer de bufeta van mostrar elevades seroreactivitats envers BKPyV (OR= 1.37; 95%CI=1.04-1.80) i MCPyV (OR=1.48; 95%CI=1.16-1.88). En LLC, es van observar seroprevalences més baixes per als 9 poliomavirus mesurats (OR rang=0.21-0.70). Els patrons serològics obtinguts en LDCBG y càncer de bufeta no permeten descartar que siguin deguts a la malaltia. Es necessita confirmació mitjançant estudis prospectius i moleculars per interpretar correctament les associacions obtingudes. Els resultats en LLC son inconclusius respecte carcinogènesi donades les baixes seroreactivitats observades. Es poc probable que els poliomavirus estudiats juguin algun paper en LLC.