Human Papilomavirus infection and Ki-67 expression in Penile Cancer: Do they relate?

Resumo

Introduction: Squamous cell carcinoma (SCC) of the penis is a rare but devastating neoplasm for the patient. Human Papillomavirus (HPV) infection can induce penile carcinogenesis and may contribute to 30 to 50% of penile cancer (PeCa) cases. The overexpression of P16^INK4a can be used as a surrogate marker for active HPV infections, although the correlation between HPV infection in PeCa still is controversial. Ki-67 is a cell proliferation marker and disease aggressiveness. Aim: Our aim was to evaluate the expression and prevalence of P16^INK4a and Ki-67 in PeCa and its correlation with disease prognosis. Methods: A retrospective study was conducted from 2010 to 2020, including 48 patients with PECa. Immunohistochemical analysis of P16^INK4a and Ki-67 was performed from paraffin-embedded tissues. Results: We observed 12 cases (25%) PeCa with P16^INK4a positive expression. The expression of P16^INK4a was not associated with any histological characteristics, except the AJCC stage and the Ki-67 expression. A high Ki-67 expression was identified in P16^INK4a positive patients, and a higher survival rate was observed in patients with low Ki-67 expression. The multivariate cox progression analysis showed that only stage N and age were significant predictors of SCC. We observed also a significant high number of penectomies, and deaths associated to PeCa. Conclusion: Our study showed a lower incidence of HPV compared to what is described in the literature. A correlation between Ki-67 and P16I^NK4a and a cell cycle deregulation mediated by high-grade HPV infection was confirmed. Overexpression of Ki-67 contributes to the prognosis of PeCa patients.