Molecular Biology of Penile Cancer

Much of the research into penile cancer has been based upon clinicopathologic factors as predictors of metastasis or survival. Focus is now shifting toward genetic and epigenetic events in penile cancer. Recently, an excellent review on this topic was published by Muneer et al.26 They discuss the complexity of interaction of HPV within the cell, much of which is derived from cervical cancer research in women. In a systematic review of 31 papers published between 1986 and 2008, constituting data from 1,466 cases, the majority HPV subtypes were HPV-16 and HPV-18.27 The incidence of HPV depends on the histological subtype, ranging from 76% being detected in basaloid SCC to as low as 25% in verrucous SCC. Overall 52% of invasive penile cancers out of 145 cases from Denmark are associated with HPV.28 HPV appears to inhibit the action of p53 on cell regulation. Interestingly, HPV-negative penile cancer is usually associated with mutation of p53. This may explain why cases of penile cancer that are HPV negative have a poorer prognosis.29 Thus virtually all penile cancer cases are associated with either a mutated p53 or inhibition of the wild-type (normal) p53. Thus the central role of p53 in the pathogenesis of penile cancer should be the focus of future research with restoration of normal function a specific goal. Future gene therapy may well be focused on this, and is likely to benefit from studies performed in more common squamous malignancies.

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