title: Penile carcinogenesis in a low-incidence area: a clinicopathologic and molecular analysis of 115 invasive carcinomas with special emphasis on chronic inflammatory skin diseases.
abstract: BACKGROUND
  Human papillomavirus (HPV) infections account worldwide for 50% of penile cancers. The role of lichen sclerosus and lichen planus in penile carcinogenesis needs further investigation.
  
  
  METHODS
  Archival formalin-fixed high-grade penile intraepithelial neoplasias, differentiated penile intraepithelial neoplasias, and invasive carcinomas from a single pathology institution in a low-incidence area for penile cancer were analyzed for 28 HPV low-risk and HPV high-risk genotypes, p16 overexpression, presence of peritumoral lichen sclerosus, lichen planus, precursor lesions, and monoclonal rearrangement of the T-cell receptor γ locus.
  
  
  RESULTS
  A total of 29 penile intraepithelial neoplasias (100%) and 69 of 115 (60%) invasive cancers contained HPV high-risk genotypes with a single HPV high-risk genotype (80% HPV16, 6% HPV33, 2% HPV45 and HPV18, 1% HPV73). Multiple HPV high-risk genotypes were identified in 4% with and in 5% without HPV16/18. p16 overexpression correlated in all but 1 case of HPV high-risk 45 cancer. No p16 overexpression and HPV genotype was found in 6 differentiated penile intraepithelial neoplasias and 46 of 115 (40%) invasive cancers, 30% of which were pT2/pT3 cancers. For 35 cancers, peritumoral tissue was available for analysis. Advanced lichen sclerosus was identified in 26, lichen planus in 9, and differentiated penile intraepithelial neoplasia in 18 carcinomas. Dense T-cell-dominant lymphocytic infiltrates were identified in 22 of 46 carcinomas and in 3 of 6 differentiated penile intraepithelial neoplasias, with 6 of 13 analyzed carcinomas/penile intraepithelial neoplasias showing a monoclonal rearrangement of the T-cell receptor γ locus.
  
  
  CONCLUSIONS
  The prevalence of HPV high-risk in penile cancers from a low-incidence area was slightly higher than the global distribution. HPV-negative carcinomas were associated with advanced lichen sclerosus and lichen planus, differentiated penile intraepithelial neoplasia, and accumulation of T lymphocytes with monoclonal rearrangement of the T-cell receptor γ locus.
authors.affiliation: Institute of Pathology, Medical University Graz, Austria.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Mannweiler
authors.forename: Stephan
authors.initials: S
authors.lastname: Sygulla
authors.forename: Christine
authors.initials: C
authors.lastname: Beham-Schmid
authors.forename: Yas
authors.initials: Y
authors.lastname: Razmara
authors.forename: Karl
authors.initials: K
authors.lastname: Pummer
authors.forename: Sigrid
authors.initials: S
authors.lastname: Regauer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001317:Austria / Q000453:epidemiology; D002278:Carcinoma in Situ / Q000453:epidemiology / Q000473:pathology* / Q000821:virology; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000473:pathology* / Q000821:virology; D015897:Comorbidity; D004279:DNA, Viral / Q000032:analysis; D006801:Humans; D008010:Lichen Planus / Q000453:epidemiology / Q000473:pathology / Q000821:virology*; D018459:Lichen Sclerosus et Atrophicus / Q000453:epidemiology / Q000473:pathology* / Q000821:virology; D008297:Male; D008875:Middle Aged; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification; D030361:Papillomavirus Infections / Q000150:complications / Q000453:epidemiology / Q000473:pathology; D010412:Penile Neoplasms / Q000453:epidemiology / Q000473:pathology* / Q000821:virology; D012307:Risk Factors; D055815:Young Adult
chemical_list: D004279:DNA, Viral