Some investigators have attempted to correlate seropositivity to oncogenic HPV with the presence of penile lesions.
22 However, this correlation is problematic because antibodies do not develop in all men with HPV infection, and some men may be tested while an immune response to HPV is still developing. By contrast, a seropositive man may not be diagnosed if lesions are no longer visible and he is therefore not tested.
22
Of more than 100 types of HPV that have been discovered, nearly 40 affect the anogenital region and cause nearly 6 million new cases of infection annually.
23 The oncogenic (high-risk) types, causing the highest percentages of penile carcinoma, are HPV-16 and HPV-18, whereas most genital warts are caused by the low-risk HPV-6 and HPV-11.
1 Most HPV infections are asymptomatic and resolve within 2 years.
24,25
The mechanisms by which HPV initiates neoplasia of penile epithelial cells have become more clear with ongoing research. Human papillomaviruses are double-stranded DNA viruses that can cause persistent infection only if the virus is successfully incorporated into the replication structure of the host epithelial cells and if the host defenses are compromised in some way, preventing clearance of infected cells by apoptosis.
26 Healthy cells contain a tumor suppression protein, p53, which serves to eliminate cells with aberrant growth tendencies. High-risk HPVs stimulate E6 and E7 oncoproteins to combine with p53, allowing the virus to overcome this regulatory mechanism.
27 This process alone has not proved sufficient to cause neoplasia, but the degradation process may be augmented by other factors, such as altered host immune status, chronic infection or inflammation (eg, caused by the presence of smegma), or smoking.
28 As a result, viral DNA is replicated, with virions assembled in infected epithelial cells of the penis—cells that normally would have stopped proliferating and been sloughed off. Note that this “immortalization” property does not take place in the low-risk HPV types
29; however, low-risk types are still associated with the formation of penile cancer, perhaps by other mechanisms.
30