title: The presence of betapapillomavirus antibodies around transplantation predicts the development of keratinocyte carcinoma in organ transplant recipients: a cohort study.
abstract: Organ transplant recipients (OTRs) have an increased risk of developing keratinocyte carcinomas (KCs). The aim of this study was to correlate infection with human papillomaviruses (HPVs) belonging to the beta genus (Beta-papillomavirus (Beta-PV)) at transplantation with later development of KCs. In a cohort study, sera collected between 1 year before and 1 year after transplantation of OTRs transplanted between 1990 and 2006 were tested for antibody responses against the L1 capsid antigen of Beta-PV and other HPV genera (Gamma-, Mu-, Nu-, and Alpha-PV) using multiplex serology. The OTRs were followed for a maximum of 22 years. Cox regression models with KC, squamous cell carcinoma (SCC), and basal cell carcinoma (BCC) as outcome variables were used. Out of 445 OTRs, 60 had developed KC: 14 developed only SCC, 24 only BCC, and 22 both types of KC. The time-dependent hazard ratio (HR) to develop either or both types of KC, adjusted for age, sex, and transplanted organ, in tested Beta-PV-seropositive OTR around the time of transplantation compared with Beta-PV-seronegative OTR was 2.9 (95% confidence interval (CI) 1.3-6.4). The HR for SCC was 2.9 (95% CI 0.99-8.5) and for BCC it was 3.1 (95% CI 1.2-8.0). There was also an association between Mu-PV seropositivity and KC, but there were no significant associations between other HPV genera tested and KC. A positive seroresponse for Beta-PV around transplantation significantly predicted the development of KC in OTRs up to 22 years later, providing additional evidence that infection with Beta-PV has a role in KC carcinogenesis.
authors.affiliation: Department of Dermatology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: r.e.genders@lumc.nl.
authors.forename: Roel E
authors.initials: RE
authors.lastname: Genders
authors.affiliation: Department of Dermatology, Leiden University Medical Center, Leiden, The Netherlands; Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Hadi
authors.initials: H
authors.lastname: Mazlom
authors.affiliation: Infection and Cancer Program, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Angelika
authors.initials: A
authors.lastname: Michel
authors.affiliation: Department of Dermatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Elsemieke I
authors.initials: EI
authors.lastname: Plasmeijer
authors.affiliation: Department of Dermatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Koen D
authors.initials: KD
authors.lastname: Quint
authors.affiliation: Infection and Cancer Program, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Pawlita
authors.affiliation: Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Els
authors.initials: E
authors.lastname: van der Meijden
authors.affiliation: Infection and Cancer Program, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Waterboer
authors.affiliation: Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Hans
authors.initials: H
authors.lastname: de Fijter
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Frans H
authors.initials: FH
authors.lastname: Claas
authors.affiliation: Department of Biostatistics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Ron
authors.initials: R
authors.lastname: Wolterbeek
authors.affiliation: Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Mariet C W
authors.initials: MCW
authors.lastname: Feltkamp
authors.affiliation: Department of Dermatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Jan Nico
authors.initials: JN
authors.lastname: Bouwes Bavinck
mesh_terms: D000914:Antibodies, Viral / Q000097:blood* / Q000276:immunology; D052686:Betapapillomavirus / Q000276:immunology*; D002280:Basal Cell Carcinoma / Q000453:epidemiology / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000473:pathology; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015603:Keratinocytes / Q000473:pathology*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D016035:Pancreas Transplantation; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D012878:Skin Neoplasms / Q000453:epidemiology* / Q000473:pathology; D013997:Time Factors; D066027:Transplant Recipients
chemical_list: D000914:Antibodies, Viral