Abstract
Human papillomaviruses (HPVs), which are small, double-stranded, circular DNA viruses infecting human epithelial cells, are associated with various benign and malignant lesions of mucosa and skin. Intensive research on the oncogenic potential of HPVs started in the 1970s and spread across Europe, including Croatia, and worldwide. Nowadays, the causative role of a subset of oncogenic or high-risk (HR) HPV types, led by HPV-16 and HPV-18, of different anogenital and head and neck cancers is well accepted. Two major viral oncoproteins, E6 and E7, are directly involved in the development of HPV-related malignancies by targeting synergistically various cellular pathways involved in the regulation of cell cycle control, apoptosis, and cell polarity control networks as well as host immune response. This review is aimed at describing the key elements in HPV-related carcinogenesis and the advances in cancer prevention with reference to past and on-going research in Croatia.
Highlights
Dubravko Forčić the infectious origin of bovine warts was initially described by O
P16 positive patients with low Ki-67 in head and neck cancers (HNCs) showed good local control without metastasis [107]. Detection of both minichromosome maintenance complex component 2 (MCM2) and topoisomerase II alpha (TOP2A) proteins represents another promising set of biomarkers, which has been linked to the severity of cervical lesions and the presence of HR human papillomavirus (HPV) [104]
Th2, Tregs, and T helper 17 (Th17) secrete IL-6, IL-8, IL-10, and IL-17, which are all pro-tumorigenic in the context of HPV-associated tumours, as they inhibit the maturation of DCs and the activation of Natural killer (NK) cells
Summary
The infectious origin of bovine warts was initially described by O. Investigation of viral aetiology of genital warts was done by H. zur Hausen et al, who subsequently postulated a possible causal role of HPVs for cervical cancer (CC) [5], which was later proven [6]. Mucosal/cutaneous or alpha-HPVs (65 types) are isolated from genital and oral lesions while the others from cutaneous specimens, mostly beta- (54 types) and gamma-HPVs (98 types) [7] These discoveries dramatically changed the worldwide approach to CC diagnosis, prognosis, and prevention and subsequently led to the production of the first prophylactic vaccine against a solid tumour that is caused by a viral infection in humans [8]. The focus was on the epigenetic studies in HPV-associated lesions and cancer in different sites [23,24,25]. This review will focus only on the essential elements of HPV-related carcinogenesis as well as the advances in cancer diagnosis and treatment, which, in addition to vaccination, are the most important in cancer prevention
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