title: Role of Human Papillomavirus in Penile Carcinomas Worldwide.
abstract: Invasive penile cancer is a rare disease with an approximately 22 000 cases per year. The incidence is higher in less developed countries, where penile cancer can account for up to 10% of cancers among men in some parts of Africa, South America, and Asia.
  
  
  
  To describe the human papillomavirus (HPV) DNA prevalence, HPV type distribution, and detection of markers of viral activity (ie, E6*I mRNA and p16(INK4a)) in a series of invasive penile cancers and penile high-grade squamous intraepithelial lesions (HGSILs) from 25 countries. A total of 85 penile HGSILs and 1010 penile invasive cancers diagnosed from 1983 to 2011 were included.
  
  
  
  After histopathologic evaluation of formalin-fixed paraffin-embedded samples, HPV DNA detection and genotyping were performed using the SPF-10/DEIA/LiPA25 system, v.1 (Laboratory Biomedical Products, Rijswijk, The Netherlands). HPV DNA-positive cases were additionally tested for oncogene E6*I mRNA and all cases for p16(INK4a) expression, a surrogate marker of oncogenic HPV activity.
  
  
  
  HPV DNA prevalence and type distributions were estimated.
  
  
  
  HPV DNA was detected in 33.1% of penile cancers (95% confidence interval [CI], 30.2-36.1) and in 87.1% of HGSILs (95% CI, 78.0-93.4). The warty-basaloid histologic subtype showed the highest HPV DNA prevalence. Among cancers, statistically significant differences in prevalence were observed only by geographic region and not by period or by age at diagnosis. HPV16 was the most frequent HPV type detected in both HPV-positive cancers (68.7%) and HGSILs (79.6%). HPV6 was the second most common type in invasive cancers (3.7%). The p16(INK4a) upregulation and mRNA detection in addition to HPV DNA positivity were observed in 69.3% of HGSILs, and at least one of these HPV activity markers was detected in 85.3% of cases. In penile cancers, these figures were 22.0% and 27.1%, respectively.
  
  
  
  About a third to a fourth of penile cancers were related to HPV when considering HPV DNA detection alone or adding an HPV activity marker, respectively. The observed HPV type distribution reinforces the potential benefit of current and new HPV vaccines in the reduction of HPV-related penile neoplastic lesions.
  
  
  
  About one-third to one-quarter of penile cancers were related to human papillomavirus (HPV). The observed HPV type distribution reinforces the potential benefit of current and new HPV vaccines to prevent HPV-related penile neoplastic lesions.
authors.affiliation: Institut Català d'Oncologia, Barcelona, Spain; CIBER en Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain. Electronic address: lalemany@iconcologia.net.
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authors.affiliation: Institut Català d'Oncologia, Barcelona, Spain.
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authors.affiliation: Eduardo Mondlane University and Maputo Central Hospital, Maputo, Mozambique.
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authors.affiliation: Instituto Potosino de Investigación Científica y Tecnológica, San Luis Potosí, Mexico.
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authors.affiliation: Cancer Research Center, University of Hawaii, Honolulu, HI, USA; Cedars Sinai Medical Center, Los Angeles, CA, USA.
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authors.affiliation: Institut Català d'Oncologia, Barcelona, Spain.
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authors.affiliation: Institut Català d'Oncologia, Barcelona, Spain.
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authors.lastname: Muñoz
authors.affiliation: Institut Català d'Oncologia, Barcelona, Spain.
authors.forename: F Xavier
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authors.affiliation: Institut Català d'Oncologia, Barcelona, Spain; CIBER en Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain.
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mesh_terms: D000349:Africa; D000368:Aged; D001208:Asia; D002277:Carcinoma / Q000821:virology*; D003430:Cross-Sectional Studies; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism; D004279:DNA, Viral / Q000032:analysis*; D005060:Europe; D005838:Genotype; D052162:Human papillomavirus 16 / Q000235:genetics / Q000302:isolation & purification*; D052163:Human papillomavirus 6 / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D007843:Latin America; D008297:Male; D008875:Middle Aged; D009656:North America; D044349:Oceania; D030361:Papillomavirus Infections / Q000150:complications* / Q000821:virology; D010412:Penile Neoplasms / Q000473:pathology / Q000821:virology*; D012367:RNA, Viral / Q000032:analysis; D012189:Retrospective Studies
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral; D012367:RNA, Viral
keywords: DNA; Human papillomavirus; Penile cancer; Vaccine; mRNA; p16