Prognostic value of p16INK4a overexpression in penile cancer


Published: April 6, 2020
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Introduction: Penile cancer is rare, accounting for less than 1% of all male cancers in industrialized countries. It is most common in areas of high prevalence of HPV, being a third of cases attributed to the carcinogenic effect of HPV. Tumour cells infected with HPV overexpress p16INK4a, as such p16INK4a has been used as a surrogate of HPV infections.
Objective: To evaluate the prognostic factor of p16INK4a overexpression in penile cancer.
Methods: Retrospective analysis of patients diagnosed with penile cancer, submitted to surgery in a Portuguese Oncological Institution in the last 20 years (n = 35). Histological review of surgical pieces and immunohistochemical identification of p16INK4a. Relation between p16INK4a and the following factors were studied: age, histological subtype, tumour dimensions, grade, TNM stage, perineural invasion, perivascular invasion, disease free survival (DFS) and cancer specific survival (CSS).
Results: p16INK4a was positive in 8 patients (22.9%). Identification of p16INK4a did not correlate with none of the histopathological factors. In this work we identified a better DFS and CSS in patients positive for p16INK4a (DFS at 36 months was 100.0% vs. 66.7%; CSS at 36 months was 100.0% vs. 70.4%), although without statistical significance (p > 0.05). In multivariate analysis of histopathological factors studied, only N staging correlated with DFS and CSS (p = 0.017 and p = 0.014, respectively).
Discussion: the percentage of cases positive for p16INK4a is smaller than the one found in literature, which can suggest a less relevant part of HPV infection in the oncogenesis of penile cancer in the studied population. Identification of p16INK4a did not relate with other clinicopathological factors. Tendency for a more favourable prognosis in patients with p16INK4a agrees with results found in literature. The most relevant factor for prognosis is nodal staging.
Conclusions: penile cancer positive for p16INK4a shows a trend for better survival, although the most relevant factor is nodal staging.


Pereira-Lourenço, M., Vieira e Brito, D., Eliseu, M., Castelo-Branco, N., Peralta, J. P., Godinho, R., Conceição, P., Reis, M., Rabaça, C., & Sismeiro, A. (2020). Prognostic value of p16INK4a overexpression in penile cancer. Archivio Italiano Di Urologia E Andrologia, 92(1), 11–16. https://doi.org/10.4081/aiua.2020.1.11

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