title: Beta Human Papillomavirus Infection Is Prevalent in Elephantiasis and Exhibits a Productive Phenotype: A Case-Control Study.
abstract: Elephantiasis is considered a cutaneous region of immune deficiency with cobblestone-like surface caused by a wart-like eruption. Verrucosis is a diffuse human papillomavirus (HPV) infection linked to immunodeficiency disorders. The objective of this study was to examine the prevalence of HPV infection in lymphedema and its pathogenic role in elephantiasis. A retrospective case-control study was performed examining lymphedematous skin and controls of peritumoral normal skin. HPV infection was evaluated at the DNA, protein, and histopathologic levels by polymerase chain reaction, immunohistochemistry, and light microscopy, respectively. Overall, 540 HPV DNAs were detected in 120 of 122 cutaneous samples (median 4 HPV DNAs per sample, range 0-9). Compared with controls, no differences existed in type or number of HPVs identified. Instead, a diverse spectrum of HPV-related histopathologies were evident, likely reflecting the multiplicity of HPV genotypes detected. Most notably, increasing histopathologic lymphedema stage significantly correlated with markers of productive HPV infection such as altered keratohyaline granules and HPV L1 capsid expression. Limitations of this study are the absence of normal skin controls not associated with neoplasia or subclinical lymphedema, and lack of assessment of HPV copy number per keratinocyte infected. In conclusion, productive HPV infection, not HPV type or numbers detected, distinguished lymphedematous skin from controls. These findings support the theory that lymphedema creates a region of depressed immunity that permits productive HPV infection, manifested clinically by diffuse papillomatosis, characteristic of elephantiasis.
authors.affiliation: *Divisions of Dermatology and Dermatopathology, Albany Medical College, Albany, NY; and †Departments of Dermatology, Microbiology/Medical Genetics, and Internal Medicine, University of Texas Health Science Center, Houston, TX.
authors.forename: John Andrew
authors.initials: JA
authors.lastname: Carlson
authors.forename: Peter
authors.initials: P
authors.lastname: Rady
authors.forename: Pooja
authors.initials: P
authors.lastname: Kadam
authors.forename: Qin
authors.initials: Q
authors.lastname: He
authors.forename: Rebecca
authors.initials: R
authors.lastname: Simonette
authors.forename: Stephen
authors.initials: S
authors.lastname: Tyring
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000276:immunology; D001706:Biopsy; D036022:Capsid Proteins / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D056915:DNA Copy Number Variations; D004279:DNA, Viral / Q000235:genetics; D018450:Disease Progression; D004604:Elephantiasis / Q000453:epidemiology* / Q000276:immunology / Q000473:pathology / Q000821:virology; D005260:Female; D005838:Genotype; D054884:Host-Pathogen Interactions; D061809:Human Papillomavirus DNA Tests; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009856:Oncogene Proteins, Viral / Q000032:analysis; D027383:Papillomaviridae / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000453:epidemiology* / Q000276:immunology / Q000473:pathology / Q000821:virology; D010641:Phenotype; D015995:Prevalence; D012189:Retrospective Studies; D012867:Skin / Q000276:immunology / Q000473:pathology / Q000821:virology*; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D036022:Capsid Proteins; D004279:DNA, Viral; C114580:HPV L1 protein, Human papillomavirus; D009856:Oncogene Proteins, Viral; C500987:monoclonal antibody D2-40