Penile cancer: potential target for immunotherapy?
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TOPIC PAPER
Penile cancer: potential target for immunotherapy? Joren Vanthoor1 · Gigi Vos1 · Maarten Albersen1 Received: 16 July 2020 / Accepted: 23 October 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Purpose Penile cancer (PeCa) is a rare malignancy with a poor prognosis in advanced disease. There is still a limited understanding of the biological mediators that are important in the prognosis and therapy of the disease. This review aims to provide a summary of the immune micro-environment, molecular oncogenesis and the role of HPV in the disease applying to the potential of the use of immunotherapy. Methods Narrative, non-systematic review based on publications retrieved by PubMed and EMBASE search. Results The molecular mechanisms underlying penile carcinogenesis are complex, and human papillomavirus (HPV) infection is a well-characterized driver of penile cancer. Up to 50% of the penile carcinomas are HPV related. There is potential to improve prevention, treatment and follow-up strategies pertaining to the role of HPV in penile cancer. Immune response modifiers such as toll-like receptor agonists are being used in a topical fashion for penile intraepithelial neoplasia while immune checkpoint inhibitors are currently under clinical investigation for its application in penile cancer. Conclusions The knowledge of prognosis-relevant biological pathways in penile cancer is expanding. HPV plays an important role in the carcinogenesis. This can lead to the identification of therapeutic targets which could significantly influence the prognosis of advanced penile cancer. Clinical trials are being conducted to pave the way for immune-modifying treatment modalities. Keywords Penile cancer · Human papillomavirus · Imiquimod · Immunotherapy
Introduction Primary penile cancer is a rare disease with an incidence of about 1/100,000–1,000,000 men annually [1]. There are approximately 26,000 new cases diagnosed each year globally, and it accounts for 0.4–0.6% of all malignancies in the Western world [2, 3]. The incidence varies strongly among different geographic areas, with an incidence up to 6% of malignancies in developing countries [4]. More than 95% of the penile cancer tumors are squamous cell carcinoma (SCC), causing significant morbidity and mortality. Important risk factors include HPV infection, lack of circumcision, phimosis, obesity, lichen sclerosus, inflammation, smoking, previous UVA phototherapy and socioeconomic status [2, 5].
Joren Vanthoor and Gigi Vos are co-first authors. * Maarten Albersen [email protected] 1
Department of Urology, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium
The rarity of this disease creates a challenge for treating physicians. There is still only a limited understanding of the biological mechanisms, micro-environment and biomarkers in penile cancer. As HPV DNA is detected in half of the squamous cell carcinoma of the penis, this infection is strongly associated with PeCa specimens [6]. This review aims to provid
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