Prospective study of Merkel cell polyomavirus and risk of Merkel cell carcinoma.
Merkel cell carcinoma (MCC) is a rare type of skin cancer that has a characteristically increased incidence among immunosuppressed subjects. The DNA of Merkel cell polyomavirus (MCV) is regularly found in most MCC tumors. We investigated whether Merkel cell polyomavirus (MCV) infection increases the risk for future MCC. Two large biobank cohorts (Southern Sweden Microbiology Biobank and the Janus Biobank), containing samples from 856,000 healthy donors, were linked to the Cancer Registries in Sweden and Norway to identify cases of MCC occurring up to 30 years after donation of a serum sample. For each of the 22 cases (nine males and 13 females), four matched controls were included. The serum samples were analyzed with an MCV neutralization assay and for IgG antibodies to MCV pseudovirions, using JC polyomavirus and cutaneous human papillomaviruses as control antigens. An increased risk for future MCC was associated both with high levels of MCV antibodies [OR 4.4, 95% CI 1.3-17.4] and with MCV neutralizing activity (OR 5.3, 95% CI 1.3-32.3). In males, MCV seropositivity was not associated to MCC risk, whereas the risk was strongly increased in females, both for high levels of MCV antibodies (OR 7.0, 95% CI 1.6-42.8) and for MCV neutralizing activity (OR 14.3, 95% CI 1.7-677). In conclusion, we found prospective evidence that MCV infection is associated with an increased risk for future MCC, in particular among females.
Department of Medical Microbiology, Skåne University Hospital, Lund University, Malmö, Sweden.
Helena
H
Faust
Kristin
K
Andersson
Johanna
J
Ekström
Maria
M
Hortlund
Trude Eid
TE
Robsahm
Joakim
J
Dillner
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000914:Antibodies, Viral / Q000097:blood*; D015266:Carcinoma, Merkel Cell / Q000097:blood / Q000209:etiology* / Q000473:pathology; D016022:Case-Control Studies; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D059965:Merkel cell polyomavirus / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D008875:Middle Aged; D009500:Neutralization Tests; D016133:Polymerase Chain Reaction; D027601:Polyomavirus Infections / Q000150:complications* / Q000276:immunology / Q000821:virology; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D012878:Skin Neoplasms / Q000097:blood / Q000209:etiology* / Q000473:pathology; D014412:Tumor Virus Infections / Q000150:complications* / Q000276:immunology / Q000821:virology
D000914:Antibodies, Viral; D004279:DNA, Viral
Merkel cell carcinoma; Merkel cell polyomavirus; nonmelanoma skin cancer; prospective case-control study; serology; viral infections