title: Human papillomavirus-16 is the predominant type etiologically involved in penile squamous cell carcinoma.
abstract: OBJECTIVE
  Human papillomavirus (HPV) infections are suggested to be involved in the development of penile squamous cell carcinoma (SCC), but comprehensive studies to define the association are limited. Therefore, we performed molecular and serologic analyses for a broad spectrum of HPV types on a large series of 83 penile SCCs, and we compared serological findings to those of age-matched male controls (N = 83).
  
  
  METHODS
  Penile SCCs were subjected to detection and typing assays for mucosal and cutaneous HPVs and to subsequent, type-specific viral load and viral gene expression assays. Sera of patients and of controls were analyzed for type-specific mucosal and cutaneous HPV L1, E6, and/or E7 antibodies using bead-based, multiplex serology.
  
  
  RESULTS
  HPV DNA of mucosal and/or cutaneous types was found in 46 of 83 (55%) penile SCCs. HPV16 was the predominant type, appearing in 24 (52%) of 46 of penile SCCs. The majority of HPV16 DNA-positive SCCs (18 of 24; 75%) demonstrated E6 transcriptional activity and a high viral load. Additionally, HPV16 molecular findings were strongly associated with HPV16 L1-, E6-, and E7-antibody seropositivity. Furthermore, serologic case-control analyses demonstrated that, in addition to the association of HPV16 with penile SCC, seropositivity against any HPV type was significantly more common in patients compared with in controls. HPV18 and HPV6 seropositivity were associated with HPV16-negative SCCs but were not correlated to molecular findings.
  
  
  CONCLUSIONS
  HPV16 is the main HPV type etiologically involved in the development of penile SCC. Although individuals who develop penile SCC show a greater prior exposure to a broad spectrum of HPV types, insufficient evidence was found to claim a role for HPV types other than HPV16 in penile carcinogenesis.
authors.affiliation: Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands. dam.heideman@vumc.nl
authors.forename: Daniëlle A M
authors.initials: DA
authors.lastname: Heideman
authors.forename: Tim
authors.initials: T
authors.lastname: Waterboer
authors.forename: Michael
authors.initials: M
authors.lastname: Pawlita
authors.forename: Pien
authors.initials: P
authors.lastname: Delis-van Diemen
authors.forename: Ingo
authors.initials: I
authors.lastname: Nindl
authors.forename: Joost A
authors.initials: JA
authors.lastname: Leijte
authors.forename: Johannes M G
authors.initials: JM
authors.lastname: Bonfrer
authors.forename: Simon
authors.initials: S
authors.lastname: Horenblas
authors.forename: Chris J L M
authors.initials: CJ
authors.lastname: Meijer
authors.forename: Peter J F
authors.initials: PJ
authors.lastname: Snijders
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000956:Antigens, Viral; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000209:etiology / Q000821:virology*; D016022:Case-Control Studies; D005838:Genotype; D005914:Globins / Q000378:metabolism; D052162:Human papillomavirus 16 / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000378:metabolism; D030361:Papillomavirus Infections / Q000150:complications; D010412:Penile Neoplasms / Q000097:blood / Q000209:etiology / Q000821:virology*
chemical_list: D000956:Antigens, Viral; D005914:Globins