HPV Infection and Penile Cancer

Much of our understanding of how HPV infection may lead to premalignant lesions and invasive tumors is based on studies of carcinogenesis in cervical cancer. However, while almost 100% of cervical SCCs are related to sexually transmitted HPV infection, rates of HPV in penile cancer are reported between 30% to 100%.1-6 The reasons for this wide range include geographical variations and different cultural attitudes towards sex between the reporting centers, as well as technical differences in the methodology used for HPV detection. A recent systematic review of established PCR techniques has found HPV DNA in approximately 50% of all penile SCCs.7 In this respect, penile tumors are more similar to vulval carcinomas, which also share a similar pathogenesis and histology.5,8

The human papilloma virus exerts its tumorigenic effect via expression of the viral oncogenes E6 and E7.9 E6 interacts with p53, while E7 interacts with retinoblastoma (RB) to block the activity of these tumor suppressor genes.10,11 The resultant deregulation of cell cycle control and apoptotic cellular mechanisms results in malignant transformation to carcinoma in situ or invasive malignancy if left untreated.12

The marked difference in the prevalence, age of peak incidence, and rate of progression of both cervical and penile tumors may underlie either differing pathogenic mechanisms or differing tissue susceptibility and pathogenic response to the same HPV infection in these two malignancies. While the cervical model of carcinogen-esis gives a good basis for tumor development and progression in penile cancer, it does not fully explain the complete pathogenesis.

Premalignant penile lesions can be broadly divided into those related to HPV infection and those which are not HPV related, but due to chronic inflammation. HPV-related lesions include:

• Giant condyloma

• Bowenoid papulosis

• Erythroplasia of Queyrat

Those due to chronic inflammation include:

• Cutaneous horn

• Leukoplakia

Much of the terminology used to describe the different premalignant lesions are eponymous and nonstandardized, and a recent reclassification system based on cell morphology, squamous differentiation, and pathogenesis has been suggested and discussed in greater detail in Chap. 3.13 In the new proposed classification system the term Penile Intraepithelial Neoplasia (PeIN) is used to describe premalignant lesions, and is further subclassified into differentiated, warty, basaloid, and mixed warty-basaloid subtypes. Differentiated PeIN is the subtype most frequently associated with chronic inflammation and not HPV, while the remaining three warty/

basaloid PeIN subtypes represent those related to HPV infection. In the remainder of this chapter however, we will use the more common and widely established terminology.

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