title: Human papillomavirus proteins are found in peripheral blood and semen Cd20+ and Cd56+ cells during HPV-16 semen infection.
abstract: BACKGROUND
  Human papillomavirus (HPV) currently represents an important risk factor for cancer development and infertility in humans. Whilst binding of HPV to spermatozoa has been associated with male infertility, an investigation about the presence of HPV-DNA in non-spermatozoal semen cells is lacking. Previous findings documented the presence of HPV in peripheral blood leukocytes. The aim of this study was to investigate the expression of HPV markers in semen and blood leukocytes during HPV-16 infection.
  
  
  METHODS
  A total of 32 subjects, 16 patients affected by HPV-16 semen infection and 16 controls, were evaluated in our andrological centre and enrolled in the study. Semen non-spermatozoal cells from all subjects were isolated and evaluated for the expression of HPV-16 markers (DNA and L1, E6 proteins) and further characterized for their molecular phenotype. Analogue determination was performed on peripheral blood mononuclear cells.
  
  
  RESULTS
  The presence of HPV-DNA by FISH analysis in a round cell population from semen, confirmed to be CD45+ leukocytes, was observed. These HPV-DNA containing-cells also displayed HPV-16-E6 and HPV-16-L1 viral proteins and, upon further investigation, were found to be CD20+ and CD56+, likely phenotypes of B cells and natural killer cells (NK) respectively. In 25% of the patient group, a very small population of peripheral blood mononuclear cells was found to be positive for HPV-DNA via FISH. These cells displayed the CD20+ and CD56+ phenotype alike. None of the control subjects displayed HPV-DNA in either semen or peripheral blood.
  
  
  CONCLUSIONS
  Considering the role of CD20+ and CD56+ cell populations in the antiviral immune response, the detection of HPV markers on leukocytes may reflect the presence of virus particles within the endosomal compartment. However, the presence of HPV markers in circulating mononuclear cells raise concerns about the risk of developing cancers to distal organs.
authors.affiliation: Department of Molecular Medicine and Centre for Human Reproduction Pathology, University of Padova, Via Gabelli 63, 35121, Padova, Italy. carlo.foresta@unipd.it.
authors.forename: Carlo
authors.initials: C
authors.lastname: Foresta
authors.forename: Alessandro
authors.initials: A
authors.lastname: Bertoldo
authors.forename: Andrea
authors.initials: A
authors.lastname: Garolla
authors.forename: Damiano
authors.initials: D
authors.lastname: Pizzol
authors.forename: Silvia
authors.initials: S
authors.lastname: Mason
authors.forename: Andrea
authors.initials: A
authors.lastname: Lenzi
authors.forename: Luca
authors.initials: L
authors.lastname: De Toni
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D018951:Antigens, CD20 / Q000276:immunology; D019002:CD56 Antigen / Q000276:immunology; D036022:Capsid Proteins / Q000235:genetics / Q000378:metabolism*; D004279:DNA, Viral / Q000032:analysis / Q000302:isolation & purification; D052162:Human papillomavirus 16 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism*; D030361:Papillomavirus Infections / Q000821:virology*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D012661:Semen / Q000821:virology*
chemical_list: D018951:Antigens, CD20; D019002:CD56 Antigen; D036022:Capsid Proteins; D004279:DNA, Viral; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins; C063317:L1 protein, Human papillomavirus type 16