title: Identification and genotyping of human papillomavirus in a Spanish cohort of penile squamous cell carcinomas: correlation with pathologic subtypes, p16(INK4a) expression, and prognosis.
abstract: BACKGROUND
  Penile squamous cell carcinoma (PSCC) is a tumor with a high metastatic potential. In PSCC the attributable fraction to human papillomavirus (HPV) is not well established.
  
  
  OBJECTIVE
  We sought to provide novel data about the prevalence of HPV in a large series of penile intraepithelial neoplasia (PeIN) and invasive PSCC, correlating the results with the histologic subtype, p16(INK4a) immunostaining, and prognosis.
  
  
  METHODS
  A total of 82 PSCC were included in the study, 69 invasive and 13 PeIN. HPV detection was performed by polymerase chain reaction with SPF-10 broad-spectrum primers followed by DNA enzyme immunoassay and genotyping with a reverse hybridization line probe assay. P16(INK4a) immunohistochemical expression on tissue microarrays was also analyzed.
  
  
  RESULTS
  HPV DNA was identified in 31 of 77 (40.2%) PSCC (22 of 67 invasive and 9 of 10 PeIN). In 25 of 31 (80.6%) cases HPV-16 was identified. HPV detection was significantly associated with some histologic subtypes: most basaloid and warty tumors were high-risk HPV (hrHPV) positive, whereas only 15% of usual PSCC were hr-HPV positive. All hrHPV-positive PSCC had an adjacent undifferentiated PeIN. Strong p16(INK4a) immunostaining correlated with hrHPV infection. Most undifferentiated PeIN showed p16(INK4a) immunohistochemical overexpression. Both hrHPV-positive and p16(INK4a)-positive tumors showed a better overall survival without reaching statistical significance.
  
  
  CONCLUSIONS
  This was a retrospective study.
  
  
  CONCLUSIONS
  Our results suggest that most hrHPV-positive PSCC develop from undifferentiated hrHPV-positive PeIN. P16(INK4a) immunostaining may be useful in identifying both etiologically related hrHPV-positive tumors and those with better outcome. The routine use of p16(INK4a) staining should be incorporated in histologic evaluation of PSCC.
authors.affiliation: Department of Dermatology, Hospital Universitari Vall d'Hebron, Barcelona, Spain. 40879cfp@comb.cat
authors.forename: Carla
authors.initials: C
authors.lastname: Ferrándiz-Pulido
authors.forename: Emili
authors.initials: E
authors.lastname: Masferrer
authors.forename: Ines
authors.initials: I
authors.lastname: de Torres
authors.forename: Belen
authors.initials: B
authors.lastname: Lloveras
authors.forename: Javier
authors.initials: J
authors.lastname: Hernandez-Losa
authors.forename: Sergio
authors.initials: S
authors.lastname: Mojal
authors.forename: Carlos
authors.initials: C
authors.lastname: Salvador
authors.forename: Juan
authors.initials: J
authors.lastname: Morote
authors.forename: Santiago
authors.initials: S
authors.lastname: Ramon y Cajal
authors.forename: Ramon M
authors.initials: RM
authors.lastname: Pujol
authors.forename: Vicente
authors.initials: V
authors.lastname: Garcia-Patos
authors.forename: Agustin
authors.initials: A
authors.lastname: Toll
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002278:Carcinoma in Situ / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D027383:Papillomaviridae / Q000235:genetics* / Q000302:isolation & purification; D030361:Papillomavirus Infections / Q000453:epidemiology*; D010412:Penile Neoplasms / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D015995:Prevalence; D011379:Prognosis; D012189:Retrospective Studies; D013030:Spain / Q000453:epidemiology
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16