Mucosal and Cutaneous Human Papillomavirus Infections and Cancer Biology

Abstract

Papillomaviridae is a family of small non-enveloped icosahedral viruses with double-stranded circular DNA. More than 200 different human papillomaviruses (HPVs) have been listed so far. Based on epidemiological data, a subgroup of alphapapillomaviruses (alpha HPVs) was referred to as high-risk (HR) HPV types. HR HPVs are the etiological agents of anogenital cancer and a subset of head and neck cancers. The cutaneous HPV types, mainly from beta and gamma genera, are widely present on the surface of the skin in the general population. However, there is growing evidence of an etiological role of betapapillomaviruses (beta HPVs) in non-melanoma skin cancer (NMSC), together with ultraviolet (UV) radiation. Studies performed on mucosal HR HPV types, such as 16 and 18, showed that both oncoproteins E6 and E7 play a key role in cervical cancer by altering pathways involved in the host immune response to establish a persistent infection and by promoting cellular transformation. Continuous expression of E6 and E7 of mucosal HR HPV types is essential to initiate and to maintain the cellular transformation process, whereas expression of E6 and E7 of cutaneous HPV types is not required for the maintenance of the skin cancer phenotype. Beta HPV types appear to play a role in the initiation of skin carcinogenesis, by exacerbating the accumulation of UV radiation-induced DNA breaks and somatic mutations (the hit-and-run mechanism), and they would therefore act as facilitators rather than direct actors in NMSC. In this review, the natural history of HPV infection and the transforming properties of various HPV genera will be described, with a particular focus on describing the state of knowledge about the role of cutaneous HPV types in NMSC.

Transcriptome analysis of HPV-induced warts and healthy skin in humans

“…The CDKN1A gene, which encodes for the cyclin-dependent kinase inhibitor p21, is a transcriptional target of the tumor suppressor protein p53 and functions to induce cell cycle arrest in the event of DNA damage [35,36]. In the context of HPV type, it appears to be that the alphapapillomaviruses, including the low-risk HPV2 and HPV57 and the high-risk HPV15 and HPV18, target the p53-p21 pathway regardless of oncogenic potential [37,38].…”

Regulation of Autophagy in Cells Infected With Oncogenic Human Viruses and Its Impact on Cancer Development

“…In this context, most of the oncogenic viruses possess the capability to inhibit autophagy mainly promoting viral replication and cellular maintenance, though this favors cancer onset. epithelial cancers (Gheit, 2019). Similar to HBV and MCPyV, HPV is involved in carcinogenesis in a state called "pseudolatency, " where the viral genome is integrated in the host cells, produces oncoviral proteins, and drives mutagenesis, although unable to replicate (Chang et al, 2017).…”

Successful treatment of verruca plana with NB‐UVB: A case report

“…It was revealed that chronic exposure to ultraviolet radiation (UVR) accelerates skin aging and even may lead to the development of melanoma and nonmelanoma skin cancers (Reich & Mędrek, 2013). There is growing evidence of an etiological role of betapapillomaviruses (β HPVs) in non-melanoma skin cancer (NMSC), together with UVR (Gheit, 2019;Hasche, Stephan, Braspenning-Wesch, et al, 2017). But NBUVB is an exception.…”