title: Human Papillomavirus Infection and p16 Expression in Extragenital/Extraungual Bowen Disease in Immunocompromised Patients.
abstract: An increased rate of second nonmelanoma skin cancers is found in immunocompromised patients. Epidemiological and molecular data implicate ultraviolet radiation as the major risk factor. In addition, there is increasing evidence supporting the role of human papillomavirus (HPV) in the pathogenesis of premalignant and malignant skin lesions in both immunocompetent and immunocompromised patients. In a retrospective cross-sectional study, the authors examined the expression of p16 by immunohistochemistry and the presence of mucosal (α-genus) and cutaneous/epidermodysplasia verruciformis (β-genus) HPV DNA by polymerase chain reaction in 29 biopsy specimens of extragenital/extraungual Bowen disease (BD) from 24 Eastern European white immunocompromised patients. Furthermore, the author evaluated the association between the expression of p16 protein and the presence of HPV DNA. Among 25 specimens from 21 patients evaluable by polymerase chain reaction, HPV DNA was detected in 10 (40%) BD lesions from 9 patients. Beta-HPV predominated over alpha-HPV types. Among 29 immunohistochemically evaluable BD specimens, 22 lesions (∼76%) from 20 patients were scored as p16 positive. HPV DNA-positive and HPV DNA-negative lesions displayed the same proportion of p16 positivity (80%) and no correlation was found between the HPV DNA presence and the p16 expression status. Our pilot study demonstrated that β-HPV infections predominate in BD cases diagnosed among immunocompromised patients, although high- and low-risk mucosal (alpha) HPV genotypes may be detected in a minority of cases. In contrast to anogenital HPV-associated lesions, positive p16 expression is not a reliable marker of high-risk α-HPV infection in BD cases, as it can be also detected in β-HPV infected and HPV-negative cases.
authors.affiliation: *Šikl's Department of Pathology, the Faculty of Medicine and Faculty Hospital in Pilsen, Charles University in Prague, Pilsen, Czech Republic; †Bioptická laboratoř, s.r.o., Pilsen, Czech Republic; ‡Department of Pathology, Louis Pasteur University Hospital, Košice, Slovakia; and §Integrated Cancer Research Center, School of Biology and Parker H. Petit Institute of Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA.
authors.forename: Marián
authors.initials: M
authors.lastname: Švajdler
authors.forename: Roman
authors.initials: R
authors.lastname: Mezencev
authors.forename: Jana
authors.initials: J
authors.lastname: Kašpírková
authors.forename: Denisa
authors.initials: D
authors.lastname: Kacerovská
authors.forename: Dmitry V
authors.initials: DV
authors.lastname: Kazakov
authors.forename: Ondrej
authors.initials: O
authors.lastname: Ondič
authors.forename: Michal
authors.initials: M
authors.lastname: Michal
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D001913:Bowen's Disease / Q000737:chemistry / Q000276:immunology / Q000821:virology*; D002472:Cell Transformation, Viral; D003430:Cross-Sectional Studies; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis*; D018153:Czech Republic; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D061809:Human Papillomavirus DNA Tests; D006801:Humans; D016867:Immunocompromised Host; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D027383:Papillomaviridae / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D030361:Papillomavirus Infections / Q000276:immunology / Q000821:virology*; D010865:Pilot Projects; D011230:Precancerous Conditions / Q000737:chemistry / Q000276:immunology / Q000821:virology*; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D012307:Risk Factors; D012878:Skin Neoplasms / Q000737:chemistry / Q000276:immunology / Q000821:virology*
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral