Presence of high‐risk human papillomavirus DNA in penile carcinoma predicts favorable outcome in survival

Abstract

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...

Human papillomavirus genotypes and HPV16 variants in penile carcinoma

“…There was a significant frequency increase of HPV infection in penile cancer patients with age (p for trend 5 0.0122) this is consistent with the hypothesis that penile cancers develop by different etiologies and that HPV-positive tumor patients have a survival benefit as recently described by Lont et al 27 The nucleotide sequence analysis of 3 genomic regions (E6, E7 and LCR region) of 18 HPV16 isolates allowed the identification of European (E-G350) and non-European (Af1 and AA) variants. The percentage of penile carcinoma testing positive for non-European variants (55.6% of HPV16-positive samples) is much higher than that reported for cervical carcinoma in the same geographical area (33.3%).…”

“…[15][16][17][18][19][20][21][22][23][24][25][26][27] HPV16 is the most prevalent type in penile carcinoma and cervical carcinoma worldwide, with exception of the study by Senba et al, which found HPV18 in 55.4% of the tumors from northern Thailand. 1,28 HPV16, however is also the most common viral genotype identified in normal and diseased mucosa of male and female anogenital tract.…”

Human Papilloma Virus: Prevalence, distribution and predictive value to lymphatic metastasis in penile carcinoma

“…At present, there are no evidences indicating the use of HPV detection in order to decide to perform lymphadenectomies. Surprisingly, Lont et al, although failed to associate HPV status and lymph node metastasis, showed better specific-disease survival in patients with ECP associated with high risk virus (p = 0.03) (17). In order to avoid bias in our study, we only evaluated inguinal disease-free survival (IDFI), that did not show differences between HPV positive and negative groups (p = 0.45).…”

Epigenetics Markers of Metastasis and HPV-Induced Tumorigenesis in Penile Cancer

“…Contrary to cervical cancers, which appear to be almost exclusively (>90%) driven by HPV, only a proportion of penile, vulvar, anal, and oropharyngeal cancers appear to be HPV driven (9,10). Interestingly, despite the clear oncogenic effects of HPV infection, HPV positivity appears to confer a survival benefit, this is particularly true for HNSCC, and also appears to be for penile cancer, although as yet only limited data are available (11).…”