Penile Cancer Epidemiology and Risk Factors

A Contemporary Review

Antoin Douglawi; Timothy A. Masterson


Curr Opin Urol. 2019;29(2):145-149. 

In This Article

Molecular and Genetic Factors

There has been recent interest in the role of molecular factors in penile cancer oncogenesis and prognosis. Many of these markers are intimately associated with HPV infection, particularly with high-risk variants. Genomic analysis studies have sought to identify altered oncogenes such as PIK3CA and linked them to Penile SqCC.[12,13] Recent studies noted its involvement specifically with HPV-induced cancers and work by other groups showed copy number gains in this oncogene's foci.[14–16] Adimonye further clarified the pathway by noting a correlation of PIK3CA copy number gain and activation of the PI3K--AKT--mTOR pathway, a process involved in early penile carcinogenesis.[17] Such advances not only help with prognostic evaluation but can offer molecular targets for new therapies.

Apolipoprotein B mRNA-editing catalytic polypeptides (APOBECs) are cytidine deaminases that have been associated with genome hypermutation in cervical cancer and thought to be brought on by infection with high-risk HPV (hrHPV). APOBEC3A was shown to restrict HPV viral proliferation and exhibit tumor suppression properties in cervical cancer.[18,19] Interestingly, analogous studies examining its role in penile cancer noted a downregulation in its expression in HPV-negative penile SqCC and maintained expression in HPV-positive SqCC.[20] Further research is ongoing to examine how HPV-infected cells can mitigate its tumor suppressive effect.

Molecular markers have also given insight into the disease course and provided prognostic information. Tumors that are hrHPV positive confer a 14% increase in 5-year disease-specific survival.[21] Ottenhof showed that immune factors such as CD163+ macrophage infiltration and nonclassical HLA class I upregulation were associated with lymph node metastases. In addition, hrHPV negativity and diffuse PD-L1 tumor cell expression were associated with poor disease-specific survival.[22]