The role of human papillomavirus in the penile cancer (summary of the PhD dissertation)

DOI: 10.22591/magyurol.2018.2.damasdim.69

Authors:
Damásdi Miklós dr., Pytel Ákos dr., Kovács Gyula dr., Szántó Árpád dr.
Pécsi Tudományegyetem Klinikai Központ Urológiai Klinika, Pécs (igazgató: Szántó Árpád dr.)

Summary

Objective: Based on our present knowledge and evidence, phimosis, chronic inflammation (balanoposthitis, balanitis xerotica obliterans), penile lesions, UVA radiation, smoking, promiscuity, prior condyloma and HPV infection are considered a clear risk factor. The question arises whether the HPV affected primary tumor, an advanced process, clinically positive or possibly the involvement of the lymph nodes of the lymph nodes affected by HPV involvement, or the presence of the same subtypes, oncogenic HPV types in both tissue environments.
Patients, methods: Between 2002 and 2012, during operations of malignant penile cancers in the Department of Urology, University of Pécs, tissue samples were taken from both the primer tumour and the regional lymph nodes. The collection and processing of tissue samples was carried out with the permission of the PTE ÁOK Ethics Committee (Ethical Approval Number: 4828).
In our clinical studies we studied the HPV expression is issue samples and biological markers that correlated with the progression of penile tumors, and we investigated the protective role of toll-like receptor 4 (TLR4) in the formation of penile tumors.
Results: In our clinical study 16/31(51.61%) patients were isolated high malignant HPV DNA from the primary tumor, and in 3/31 cases were detected HPV from its regional (inguinal) lymph nodes. In further molecular biological studies and typing processes, in 13 of the 16 high-malignant HPV positive primary tumors, the high sensitivity test method was used to characterize. Types of HPV 16 in all 10 patients (76.92%) and 3 (23.07%) HPV 51, 82, 59 types were confirmed. In the 3 patients with HPV analysis of both primary and lymph node positive HPV 16 types were positive. In the clinical and pathological studies associated with molecular biology, 47% pTa-pT1 and 53% pT2-pT4 localized HPV positive cases were confirmed. A reverse correlation between HPV infection / TLR4 expression in penile cancer can be observed (compared to cervical cancer). TLR4 expression can be used as a biological marker to detect Of the biological markers involved in the clinical trial, the mTOR, EZH2 and RARRES1 immunohistological expression have a significant correlation with the progression of the penile tumors.
Conclusions: Both HPV-associated and HPV-independent mechanisms can lead to malignant processes (different pathways). We first introduced the difference between HPV infection and TLR4 expression in the penile tumor. Increased TLR4 expression indicates HPV negative tumors, and p16INK4a expression increases in HPV positive penile cancer. Our data suggest that TLR4 receptor expression protects the long-term presence of viral infection. We identified three new prognostic markers. Patient vaccination in the light of this clinical study would be absolutely justified, as the incidence of HPV 16/18 types in our region is far more common with other non-HPV 16-18 types. In the case of mTOR positivity (66%) the possibility of therapeutic use of mTOR inhibitors may be included.

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