title: Improved detection reveals active β-papillomavirus infection in skin lesions from kidney transplant recipients.
abstract: The aim of this study was to determine whether detection of β-HPV gene products, as defined in epidermodysplasia verruciformis skin cancer, could also be observed in lesions from kidney transplant recipients alongside the viral DNA. A total of 111 samples, corresponding to 79 skin lesions abscised from 17 kidney transplant recipients, have been analyzed. The initial PCR analysis demonstrated that β-HPV-DNA was highly present in our tumor series (85%). Using a combination of antibodies raised against the E4 and L1 proteins of the β-genotypes, we were able to visualize productive infection in 4 out of 19 actinic keratoses, and in the pathological borders of 1 out of 14 squamous cell carcinomas and 1 out of 31 basal cell carcinomas. Increased expression of the cellular proliferation marker minichromosome maintenance protein 7 (MCM7), that extended into the upper epithelial layers, was a common feature of all the E4-positive areas, indicating that cells were driven into the cell cycle in areas of productive viral infections. Although the present study does not directly demonstrate a causal role of these viruses, the detection of E4 and L1 positivity in actinic keratosis and the adjacent pathological epithelium of skin cancer, clearly shows that β-HPV are actively replicating in the intraepidermal precursor lesions of kidney transplant recipients and can therefore cooperate with other carcinogenic agents, such as UVB, favoring skin cancer promotion.
authors.affiliation: Virology Unit, Department of Translational Medicine, Medical School of Novara, Novara, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Borgogna
authors.affiliation: Virology Unit, Department of Translational Medicine, Medical School of Novara, Novara, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Lanfredini
authors.affiliation: Virology Unit, Department of Translational Medicine, Medical School of Novara, Novara, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Peretti
authors.affiliation: 1] Virology Unit, Department of Translational Medicine, Medical School of Novara, Novara, Italy [2] Department of Public Health and Pediatric Sciences, Medical School of Turin, Turin, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: De Andrea
authors.affiliation: Dermatology Unit, Department of Translational Medicine, Medical School of Novara, Novara, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Zavattaro
authors.affiliation: Dermatology Unit, Department of Translational Medicine, Medical School of Novara, Novara, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Colombo
authors.affiliation: Nephrology Unit, Department of Translational Medicine, Medical School of Novara, Novara, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Quaglia
authors.affiliation: Pathology Unit, Department of Health Sciences, Medical School of Novara, Novara, Italy.
authors.forename: Renzo
authors.initials: R
authors.lastname: Boldorini
authors.affiliation: Pathology Unit, Department of Health Sciences, Medical School of Novara, Novara, Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: Miglio
authors.affiliation: Division of Virology, National Institute for Medical Research, London, UK.
authors.forename: John
authors.initials: J
authors.lastname: Doorbar
authors.affiliation: Department of Dermatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Jan N Bouwes
authors.initials: JN
authors.lastname: Bavinck
authors.affiliation: 1] Department of Dermatology, Leiden University Medical Center, Leiden, The Netherlands [2] DDL Diagnostic Laboratory, Rijswijk, The Netherlands.
authors.forename: Koen D
authors.initials: KD
authors.lastname: Quint
authors.affiliation: DDL Diagnostic Laboratory, Rijswijk, The Netherlands.
authors.forename: Maurits N C
authors.initials: MN
authors.lastname: de Koning
authors.affiliation: Department of Public Health and Pediatric Sciences, Medical School of Turin, Turin, Italy.
authors.forename: Santo
authors.initials: S
authors.lastname: Landolfo
authors.affiliation: Virology Unit, Department of Translational Medicine, Medical School of Novara, Novara, Italy.
authors.forename: Marisa
authors.initials: M
authors.lastname: Gariglio
mesh_terms: D000368:Aged; D052686:Betapapillomavirus / Q000737:chemistry / Q000235:genetics / Q000254:growth & development / Q000302:isolation & purification*; D014408:Biomarkers, Tumor / Q000032:analysis; D036022:Capsid Proteins / Q000032:analysis; D002280:Basal Cell Carcinoma / Q000737:chemistry / Q000473:pathology / Q000821:virology*; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000473:pathology / Q000821:virology*; D004279:DNA, Viral / Q000302:isolation & purification*; D005260:Female; D006785:Hospitals, University; D061809:Human Papillomavirus DNA Tests; D006801:Humans; D007150:Immunohistochemistry; D007558:Italy; D055623:Keratosis, Actinic / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D064168:Minichromosome Maintenance Complex Component 7 / Q000032:analysis; D009856:Oncogene Proteins, Viral / Q000032:analysis; D030361:Papillomavirus Infections / Q000473:pathology / Q000821:virology*; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D012307:Risk Factors; D012878:Skin Neoplasms / Q000737:chemistry / Q000473:pathology / Q000821:virology*; D014779:Virus Replication
chemical_list: D014408:Biomarkers, Tumor; D036022:Capsid Proteins; D004279:DNA, Viral; C114580:HPV L1 protein, Human papillomavirus; D009856:Oncogene Proteins, Viral; C101624:MCM7 protein, human; D064168:Minichromosome Maintenance Complex Component 7