Presence Of Hpv With Overexpression Of P16(Ink4a) Protein And Ebv Infection In Penile Cancer-A Series Of Cases From Brazil Amazon

BackgroundIn Brazil, penile cancer (PC) is not uncommon. The highest incidence of PC is in the North and Northeast of the country. In addition to phimosis, the Human Papillomavirus (HPV) and Epstein-Baar Virus (EBV) infections are also related as risk factors for PC. The overexpression of p16(INK4a) is a surrogate sensitive marker of HPV infection in PC.ObjectivesTo correlate p16(INK4a) overexpression and HPV infection status with EBV infection in a series of PC patients from the Amazon region.MethodsTumor tissues from 47 PC cases were analyzed for the presence of HPV and EBV DNA by PCR. All PC patients were diagnosed between 2013 and 2018 at a public reference cancer center hospital in Manaus, Amazonas-Brazil. HPV was genotyped using E7 HPV16/HPV18 type-specific real-time PCR and the PapilloCheck (R) HPV-Screening assay. p16INK4a expression was evaluated by immunohistochemistry using the automated Ventana (R) BenchMark Ultra.ResultsThe mean age of patients at the time of diagnosis was 57.4 years +/- SD 17.8 ranging from 20 to 90 years old. Most of the patients (64%) came from rural areas of the Amazonas State. Thirty patients had phimosis (64%). Among the patients with phimosis, 43% (13/30) underwent circumcision, three during childhood and 10 in adulthood. 60% of the patients were smokers or ex-smokers. HPV infection was observed in 45% (21/47) of cases. HPV16 was detected in 13 patients (61%). Other HPV types detected were HPV 6, 11, 42, 51, 53, 68 and 44/55. EBV infection was observed in 30% (14/47) of the patients with PC. Co-infection with HPV and EBV was observed in 28% (6/21) cases. p16(INK4a) was only investigated in 26 samples. The p16(INK4a) overexpression was observed exclusively in HPV 16 positive cases and four HPV negative cases. In the survival analysis, the follow-up time was 35.4 months/patient. The mortality rate during the follow up time was 38%.Conclusionsp16(INK4a) positivity presented a high correlation to HPV 16 DNA detection, reinforcing its use as a surrogate marker for HPV-driven cancers. Infection with EBV was quite frequent and its role in epithelial penile oncogenesis needs to be demonstrated.