This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Heideman, D. A.M. Articles by Snijders, P. J.F. Search for Related Content PubMed PubMed Citation Articles by Heideman, D. A.M. Articles by Snijders, P. J.F.

Human Papillomavirus-16 Is the Predominant Type Etiologically Involved in Penile Squamous Cell Carcinoma

Daniëlle A.M. Heideman, Tim Waterboer, Michael Pawlita, Pien Delis-van Diemen, Ingo Nindl, Joost A. Leijte, Johannes M.G. Bonfrer, Simon Horenblas, Chris J.L.M. Meijer, Peter J.F. Snijders

From the Department of Pathology, VU University Medical Center; and the Department of Urology and the Division of Diagnostic Oncology, the Netherlands Cancer Institute, Amsterdam, the Netherlands; the Division of Genome Modifications and Carcinogenesis, Research Program Infection and Cancer, German Cancer Research Center (DKFZ), Heidelberg; and the Department of Dermatology, University Hospital Charité, Berlin, Germany

Address reprint requests to Daniëlle A.M. Heideman, PhD, Department of Pathology, VU University Medical Center, de Boelelaan 1117, 1081 HV Amsterdam, the Netherlands; e-mail: dam.heideman{at}vumc.nl

Purpose: 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.

Conclusion: 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' disclosures of potential conflicts of interest and author contributions are found at the end of this article.