Which of the following viruses is consistently found on histological review in up to 50% of specimens and has a causal role in the pathogenesis of penile squamous cell carcinoma?
A. Human papillomavirus (HPV) type 18Answer B
HPV type 16 appears most prevalent in Europe, North and South America and India. Many studies to date have found HPV type 16 present in up to 50% of cases, when penile SCC histology has been retrospectively reviewed. Although several risk factors for the development of penile SCC are well known (see list below) the exact pathogenesis is largely unknown. There appears to be at least two pathways, an HPV associated and a (non-HPV associated) chronic inflammatory associated pathway. The likely HPV related proteins involved are E6 and E7. They are known to bind to and inactivate the host cell tumour suppressor genes p53 and pRb both are negative regulators of cellular proliferation.
Recent work by Calmon and associates found a link between the HPV 16 related E6 protein and the ANXA1 gene. ANXA1 is one of the Annexin super family proteins involved with differentiation, apoptosis, proliferation and inflammation. It is proposed that E6 can interfere with the regulation of expression of genes by interacting and binding to TNF alpha-receptor 1, FAS-associated protein with death domain (FADD) and Caspase 8 and via degradation of pro-apoptotic BAX and BAK. Other recognised risk factors include smoking, increasing age >60 years, poor personal hygiene, phimosis (present in 25% of penile cancer patients), PUVA therapy, BXO or lichen sclerosus et atrophicus. The exact pathologic role of chronic inflammatory conditions like BXO in the aetiology of penile cancer remains largely unknown.