Human Papilloma Virus HPV Infection

HPV infection occurs in 15-85% of cases of SCC penis. HPV-16 and 18 are the most frequently detected types. Specifically, HPV-16 is present in 25-95% of cases and HPV-18 in the remaining 5-75% of the cases. Rarely, other HPV types are detected in penile cancer.37

In contrast to the established role of HPV as a risk factor, little is known about its prognostic significance in penile SCC. In 1992 Wiener et al. documented no significant difference in survival between patients with HPV-positive and those with HPV-negative tumors.38 Bezerra et al. in 2001 hypothesized that the presence of HPV DNA in the primary tumor could have a prognostic impact. Their study showed node metastases in 73.8% of HPV-negative and 26.2% of HPV-positive tumors, but such a difference was not statistically significant (p = 0.38). They also failed to observe significant survival differences between the two groups of patients.10 Similar results were reported by Lopes et al. in a series of 82 patients who had undergone penectomy and inguinal lymph node dissection. In this series HPV-positive tumors had inguinal metastases in 44% of cases, compared to 54.4% in HPV-negative tumors. Moreover, 5-year cancer-specific survival rates were 44.7% and 53.1%, respectively (p = 0.271).20

A more recent study was conducted in the Netherlands on 171 patients treated for penile cancer between 1963 and 2001. Positive lymph nodes were found in 71% of HPV-negative patients and 29% of HPV-positive ones (p = 0.90).24 Also, Protzel et al. did not find any correlation between the presence of HPV DNA and node involvement.39

Table 10.2 Stratification of patients with penile cancer combining pathological extension (pT) and grading (G) of primary tumor

Risk group

Solsona et al. classification49

EAU classification2

Ornellas et al.30



Tis - TaG1-2 - T1G1

T1G1, T1G2


T1G2-3 or T2-3G1


T2-3G1, T2-3G2



T2-T3 or G3

T1-2G3, T4G1-3

Concerning cancer-specific survival, Lont et al. reported 5-year cancer-specific survival rates of 92% for HPV-positive and 78% for HPV-negative patients (p = 0.03). In this study, HPV was able to predict survival regardless of primary tumor pathological stage, venous embolization, and regional lymph node involvement.24 Currently, there is no scientific explanation concerning why HPV-negative patients should have lower cancer-specific survivals.

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