Affiliation:
1. 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
Abstract
PurposeHuman 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).MethodsPenile 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.ResultsHPV 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.ConclusionHPV16 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.
Publisher
American Society of Clinical Oncology (ASCO)
Reference32 articles.
1. Dillner J, von KG, Horenblas S, Meijer CJ: Etiology of squamous cell carcinoma of the penis. Scand J Urol Nephrol 189,2000-193, (suppl 2)
2. Penile cancer: Importance of circumcision, human papillomavirus and smoking inin situ and invasive disease
3. Role of human papillomavirus in penile cancer, penile intraepithelial squamous cell neoplasias and in genital warts
4. Reactivity to human papillomavirus type 16 L1 virus-like particles in sera from patients with genital cancer and patients with carcinomas at five different extragenital sites
5. Carter JJ, Madeleine MM, Shera K, et al: Human papillomavirus 16 and 18 L1 serology compared across anogenital cancer sites. Cancer Res 61:1934,2001-1940,
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