Detectionof Human papillomavirusand epstein-Barr virusin malignantlesionsofthe male genital tract

Abstract

Penile cancer is an uncommon and potentially mutilating disease. Although its occurrence is relatively rare worldwide, it can be high in some developing countries. In the last years, evidence has accumulated pointing an etiological oncogenic role for HPV in cervical cancer. Nevertheless, few studies have been conducted concerning HPV involvement in penile carcinoma. Specific HPV genotypes have been described in 40 to 70% of penile malignant lesions, with a higher prevalence of HPV 16 and 18. It is assumed that the presence of cofactors, mainly coinfections with HIV or Epstein-Barr virus (EBV) can play a role in the progression of penile neoplasia. EBV has been linked to several human malignancies and studies have proposed its involvement in anogenital carcinogenesis. The objective of this study was to determine HPV prevalence in penile malignant lesions obtained from patients attended at the National Cancer Institute. Simultaneously, we evaluated the presence of EBV as a possible agent associated with penile carcinoma. To achieve results, Polymerase Chain Reaction (PCR) and the Restriction Fragment Length Polymorphisms (RFLP) were used. A hundred thirty-five samples were selected from 135 patients attended at INCA between 2005 and 2010. Patients mean age was 58.5 years old. HPV infection was demonstrated by using generic MY09/11 PCR. Samples were then typed by specific PCR using primers for HPV 16, 18, 33, 35, 45 and 58. Undetermined types were submitted to RFLP analysis. From the 135 samples, 82 were MY(+) (60.7%): 27 presented HPV 16 (29.7%), 5 HPV 18 (5.5%), 21 HPV 45 (23.1%) and 9 HPV 6 (99%). Seven mixed infections were detected (9.2%). Eleven cases remained untyped (HPVX) (13.4%). Regarding EBV, 46.7% samples presented EBV DNA, EBV-1 was the most prevalent type (74.6%). Thirty-six samples were coinfected by both HPV and EBV (34.1%). We investigated the possible correlation between the histological grade of the lesions with HPV and EBV DNA, but no statistical significance was found (p > 0.05). Concerning the age of the studied patients, no clear association was observed for either HPV or EBV. HPV 16 prevalence rates here described are in agreement with worldwide literature, that places HPV 16 as the most frequent HPV in cervical as well as in penile cancer. A high HPV 45 prevalence associated to a small HPV 18 detection were observed by our group, showing a new trend in these viruses circulation, a data recently described also for cervical cancer cases worldwide. The possible synergistic action of HPV and EBV viruses in carcinogenesis establishment has been suggested for cervical carcinoma. In our samples, EBV was equally detected in all lesions subtypes, including in situ carcinoma and non-invasive verrucous carcinomas, suggesting that its presence might not be due to a late infection/reactivation, but can accomplish cancer natural history. It is worth noting that penile carcinoma etiology has not been fully elucidated and HPV and EBV are still controversial agents. Hence more studies are needed to confirm or refuse their possible role in carcinogenesis, mainly nowadays when prophylactic HPV vaccines are available.