Early resection of lymph node metastases in patients with penile carcinoma improves survival.

There is evidence that a subset of penile carcinomas is caused by infection with high-risk human papillomavirus (HPV). However, extensive studies on the possible influence of HPV infection on clinical outcome of penile cancer are lacking. This investigation is aimed to examine the prevalence of high-risk HPV in a large series of penile squamous-cell carcinomas (SCCs) and to determine the relationship between HPV and survival. Formalin-fixed, paraffinembedded tumor specimens of 171 patients with penile carcinoma were tested for high-risk HPV DNA presence by GP51/61-PCR. The clinical course of the patients and the histopathological characteristics of the primary tumors were reviewed. High-risk HPV DNA was detected in 29% of the tumors, with HPV 16 being the predominant type, accounting for 76% of high-risk HPV containing SCCs. Disease-specific 5-year survival in the high-risk HPVnegative group and high-risk HPV-positive group was 78% and 93%, respectively (log rank test p 5 0.03). In multivariate analysis, the HPV status was an independent predictor for disease-specific mortality (p 5 0.01) with a hazard ratio of 0.14 (95% CI: 0.03-0.63). Our results indicate that the presence of high-risk HPV (29%) confers a survival advantage in patients with penile carcinoma. ' 2006 Wiley-Liss, Inc.Key words: penile carcinoma; HPV; survival Squamous-cell carcinoma (SCC) of the penis is uncommon and accounts for less than 1% of adult male cancers in developed countries. The incidence in Europe is 1 per 100,000 per year. 1 The highest incidence occurs in the seventh decade. The development is most likely a stepwise chain of events over a period of years from preneoplastic lesions to SCC. The etiology of penile SCC appears to be multifactorial, with a history of smoking, phimosis and poor hygiene are commonly associated with this tumor. 2,3 Recent data have also provided corroborative evidence for a role of high-risk human papillomavirus (HPV) in the pathogenesis of a subset of penile SCC. 4,5 These high-risk HPVs are known to possess transforming capacity and are a necessary but insufficient cause of cervical SCC. 6,7 More recently, also a role of these viruses has been implicated in the development of other SCCs, such as those of the head and neck and vulva, next to penile SCCs. In contrast to cervical cancers, almost all of which contain highrisk HPV, the reported high-risk HPV prevalence in the other mentioned SCCs is much lower. This suggests that the other SCCs are etiologically heterogeneous, with only a subset of cases linked to high-risk HPV. However, the exact proportion of these noncervical cancers that can be attributed to high-risk HPV is still a matter of debate since reported prevalence rates are highly variable, possibly as a result of the different testing methods that have been applied. Moreover, for penile carcinomas the histological subtype seems to be a determinant for HPV presence. Nevertheless, keratinizing or not-otherwise-specified penile SCCs, which represent the most common penile SCCs, generally show a...

A comprehensive analysis of 53 penile carcinomas was performed to determine which mechanisms might be involved in the disruption of the p16(INK4A)/cyclin D/Rb pathway. To that end, human papillomavirus (HPV) presence, p16(INK4A) expression and promoter methylation, and expression of the BMI-1 polycomb gene product were studied. Sixteen (30%) of the carcinomas were found to harbour high-risk HPV DNA, 15 of which contained HPV 16. HPV 16 E6/E7 oncogene transcripts were detected in 13 (87%) of the carcinomas that contained HPV 16. Strong immunostaining for p16(INK4A) was significantly more frequent in carcinomas that contained high-risk HPV DNA (p < 0.001) and amongst those with HPV 16 DNA, it was more frequent in lesions in which E6/E7 transcripts were detectable (p = 0.029). This supports an active role for HPV E7 in interfering with the p16(INK4A)/cyclin D/Rb pathway. Methylation of the p16(INK4A) promoter or overexpression of the BMI-1 polycomb gene product may provide alternative modes of interference with this pathway. These phenomena were mutually exclusive and found in the absence of HPV in 15% and 10% of the penile carcinomas, respectively. These data indicate that there are at least three plausible mechanisms by which the p16(INK4A)/cyclin D/Rb pathway can become disrupted during penile carcinogenesis.

Patients with only 1 or 2 inguinal lymph nodes involved without extracapsular growth and no poorly differentiated tumor within these nodes are at low risk of pelvic lymph node involvement and have a good prognosis with a 5-year survival rate of approximately 90%. Pelvic lymph node dissection seems to be unnecessary in these cases.