Molecular Genetics of Penile Cancer

Abstract

Penile cancer is a rare malignancy in the United States and Europe but has a much higher prevalence in certain geographical areas including South America and Africa. Compared with other urological malignancies, there remains a paucity of information regarding the molecular mechanisms involved in penile cancer carcinogenesis. It is generally understood that there are two separate molecular pathways that contribute to carcinogenesis, one of which is largely related to human papillomavirus (HPV) infection. The second mechanism is much less clearly understood and is related to a combination of factors including those influenced by environmental effects and somatic or epigenetic changes. However, there also remains an element of interplay between the two mechanisms that adds to the complexity of understanding the disease. The aim of this review is to outline the current understanding of the genetic factors, current research and future directions involved in understanding the disease.

Key Concepts

  • Penile cancer is a rare entity and the mechanisms behind its carcinogenesis are not completely understood.
  • It is generally understood that the pathogenesis of penile cancer may related to both HPV mediated and non-mediated mechanisms.
  • The ability of the human papillomavirus to lead to malignancy is dependent on breakdown of normal cell degradation mechanisms as well as cell cycle alterations leading to uninhibited cell proliferation.
  • Non‐HPV mediated pathogenesis has numerous potential mechanisms and remains an ongoing area of study.
  • Continued focus on centers of excellence as well as international collaborations will be needed to continue to develop a full understanding of the disease.

Keywords: penile cancer; malignancy; human papillomavirus; tumorigenesis; mutations; mTOR; inflammation

Figure 1. This illustration outlines the complex mechanisms involved in the current understanding of penile cancer tumorigenesis. Shown are both intercellular and extracellular mechanisms as well as those mediated by human papillomavirus (HPV) factors and those that are independent of this. Reproduced from C Protzel and P E Spiess (2013). Molecular Research in Penile Cancer—Lessons Learned from the Past and Bright Horizons of the Future? Int. J. Mol. Sci. 2013, 14(10), 19494–19505.
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Further Reading

Kuasne H, Marchi FA, Rogatto SR and de Syllos Colus IM (2013) Epigenetic Mechanisms in Penile Carcinoma. International Journal of Molecular Sciences 14 (6): 10791–10808. DOI: 10.3390/ijms140610791.

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McCormick, Barrett, Baumgarten, Adam, and Spiess, Philippe E(May 2017) Molecular Genetics of Penile Cancer. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0024928]