Implications for human papillomavirus in penile cancer

Flaherty, Amber; Kim, Timothy; Giuliano, Anna; Magliocco, Anthony; Hakky, Tariq S.; Pagliaro, Lance C.; Spiess, Philippe E.

doi:10.1016/j.urolonc.2013.08.010

Cited by 60 publications

(37 citation statements)

References 47 publications

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“…It is well documented in HNSCC and cervical cancers that HPV infection results in the epigenetic reprogramming of the host cell during malignant transformation resulting in a distinct HPV-induced epigenetic phenotype (20,46). In this cohort, we found HPV infection in 23% of samples which was lower than expected although the incidence of HPV-positive penile cancer ranges from 14% to 100% and is also dependent on prior circumcision which was not recorded in our cohort (47). Only HPV16 was detected in our cohort and HPV16 represents the predominant subtype in penile cancer and head and neck cancers (20,45,48).…”

Section: Discussioncontrasting

confidence: 56%

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

Feber

Arya

Winter

et al. 2015

Clinical Cancer Research

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Purpose: Penile cancer is a rare malignancy in the developed world with just more than 1,600 new cases diagnosed in the United States per year; however, the incidence is much higher in developing countries. Although HPV is known to contribute to tumorigenesis, little is known about the genetic or epigenetic alterations defining penile cancer.Experimental Design: Using high-density genome-wide methylation arrays, we have identified epigenetic alterations associated with penile cancer. Q-MSP was used to validate lymph node metastasis markers in 50 cases. A total of 446 head and neck squamous cell carcinoma (HNSCC) and cervical squamous cell carcinoma (CESCC) samples were used to validate HPV-associated epigenetic alterations.Results: We defined 6,933 methylation variable positions (MVP) between normal and tumor tissue, which includes 997 hypermethylated differentially methylated regions associated with tumor supressor genes, including CDO1, AR1, and WT1. Analysis of penile cancer tumors identified a 4 gene episignature which accurately predicted lymph node metastasis in an independent cohort (AUC of 89%). Finally, we explored the epigenetic alterations associated with penile cancer HPV infection and defined a 30 loci lineage-independent HPV specific epi-signature which predicts HPV status and survival in independent HNSCC, CESC cohorts. Epi-signature-negative patients have a significantly worse overall survival [HNSCC P ¼ 0.00073; 95% confidence interval (CI), 0.021-0.78; CESC P ¼ 0.0094; HR ¼ 3.91, 95% CI ¼ 0.13-0.78], HPV epi-signature is a better predictor of survival than HPV status alone.Conclusions: These data demonstrate for the first time genome-wide epigenetic events involved in an aggressive penile cancer phenotype and define the epigenetic alterations common across multiple HPV-driven malignancies.

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Section: Discussioncontrasting

confidence: 56%

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

Feber

Arya

Winter

et al. 2015

Clinical Cancer Research

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“…This may partially be explained by the fact that, within the general population, HPV viral infection is consistently expressed in higher amounts in the penile epithelium of asymptomatic men than in the cytologically normal cervix of women. 9 Castellsagu e et al 19 found that an inverse association between circumcision and the risk of cervical cancer was significant among women whose male partners engaged in sexual practices known to increase the risk of infection with HPV, such as having had multiple sexual partners.…”

Section: Commentmentioning

confidence: 99%

“…Moreover, 3 current reviews stated that many of these aforementioned types of HPV were considered with PSCC. 2,3,9 Urinary tract infection (UTI) represents the most common bacterial infection in children. In the first 3 months of life, UTIs were present in 2.4% of circumcised boys, and 20.1% of uncircumcised boys, who presented with fever.…”

mentioning

confidence: 99%

High-risk Oncogenic Human Papilloma Virus Infection of the Foreskin and Microbiology of Smegma in Prepubertal Boys

Balcı

Tuncel

Baran

et al. 2015

Urology

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“…HPV infection has been consistently linked to pSCC. The proportion of patients in a pSCC cohort where HPV can be detected varies with method of detection, tumour development and geography; the range is wide, from 30% to 100% HPV association [27,28].…”

Section: Human Papilloma Virus and Genital Wartsmentioning

confidence: 99%

A urologist’s contemporary guide to penile cancer

Jakobsen¹

2015

Scandinavian Journal of Urology

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Few urologists deal with penile cancer on a daily basis. Owing to the rarity of the disease and its diversity in presentation, clinical experience accumulates slowly and new paradigms spread sporadically. This review provides a concise update on the background, clinical features and multidisciplinary management strategies of penile cancer. The evidence base of penile cancer management recommendations is devoid of randomized controlled trials and relies mainly on retrospective cohort studies from single institutions. In recent years, international multicentre collaboration has increased the quality of evidence. Larger study cohorts allow researchers to engage in subgroup analysis of patients with poor prognosis, of which the literature so far has been scarce. Comprehensive evidence-based guidelines are available through the European Association of Urology. This review highlights the importance of early and minimally invasive regional lymph-node staging of all patients of stage T1G2 or higher, and underlines the therapeutic potential of inguinal lymph-node dissection in lymph-node positive patients. A discussion of the oncological safety of current trends towards more phallus-sparing treatment techniques emphasizes the importance of proper case selection, thorough patient information, consequent follow-up and the possibility of a reconstructive procedure after organ-sparing ablative penile surgery. The aetiological role of human papilloma virus (HPV) is touched upon and the evidence for circumcision and HPV vaccination of boys is briefly weighed. The value of multidisciplinary treatment of advanced penile cancer is underlined and the role of chemotherapy, radiotherapy and radiochemotherapy is discussed. Finally, the perspectives for hybrid tracer sentinel node, robot-assisted lymph-node surgery and targeted therapies are addressed.

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Implications for human papillomavirus in penile cancer

Cited by 60 publications

References 47 publications

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

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

High-risk Oncogenic Human Papilloma Virus Infection of the Foreskin and Microbiology of Smegma in Prepubertal Boys

A urologist’s contemporary guide to penile cancer

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