Molecular mechanisms of HPV mediated neoplastic progression

Abstract

Human Papillomavirus is the major etiological agent in the development of cervical cancer but not a sufficient cause. Despite significant research, the underlying mechanisms of progression from a low-grade squamous intraepithelial lesion to high grade squamous intraepithelial lesion are yet to be understood. Deregulation of viral gene expression and host genomic instability play a central role in virus-mediated carcinogenesis. Key events such as viral integration and epigenetic modifications may lead to the deregulation of viral and host gene expression. This review has summarized the available literature to describe the possible mechanism and role of viral integration in mediating carcinogenesis. HPV integration begins with DNA damage or double strand break induced either by oxidative stress or HPV proteins and the subsequent steps are driven by the DNA damage responses. Inflammation and oxidative stress could be considered as cofactors in stimulating viral integration and deregulation of cellular and viral oncogenes during the progression of cervical carcinoma. All these events together with the host and viral genetic and epigenetic modifications in neoplastic progression have also been reviewed which may be relevant in identifying a new preventive therapeutic strategy. In the absence of therapeutic intervention for HPV-infected individuals, future research focus should be directed towards preventing and reversing of HPV integration. DNA damage response, knocking out integrated HPV sequences, siRNA approach, modulating the selection mechanism of cells harboring integrated genomes and epigenetic modifiers are the possible therapeutic targets.

Head and neck cancer during pregnancy

“…77 Additionally, in vitro studies have shown that the development of HPV-related cancers also requires estrogens in the earliest stages of carcinogenesis. 77 Additionally, in vitro studies have shown that the development of HPV-related cancers also requires estrogens in the earliest stages of carcinogenesis.…”

Felis catus papillomavirus type-2 but not type-1 is detectable and transcriptionally active in the blood of healthy cats

“…Generally, it harbours two late (L) genes, encoding for capsid structural proteins L1 and L2, and up to eight early (E) genes involved in viral replication and transcriptional regulation (Buck, Day, & Trus, 2013;Nguyen, Ramirez-Fort, & Rady, 2014;Wang & Roden, 2013). Among these, E2 is a transcription factor that regulates viral genome persistence and duplication, while E5, E6 and E7 are considered to be oncogenes because they are able to impair cell proliferation and apoptosis, thus contributing to cancer development (McBride, 2013;Senapati, Senapati, & Dwibedi, 2016). E5 is the major oncogene of bovine PVs (BPVs) causing skin and mucosal cancer in cattle and sarcoids in equids (Bocaneti et al, 2016;Corteggio, Altamura, Roperto, & Borzacchiello, 2013); E6 and E7 are the main oncogenes responsible for cell transformation triggered by human PVs (HPVs) in skin, oropharyngeal and cervical cancer as well as in cottontail rabbit PV-induced cutaneous squamous cell carcinoma (SCC) (Ganzenmueller et al, 2008;Rector & Van Ranst, 2013;Tommasino, 2014).…”

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“…HPV dependent carcinogenesis starts with the infection of HPV in episomal form which initiates the transcription of viral gene products. This is followed by subsequent genomic integration of HPV oncogenes into the host genome [42]. Pregnancy can hasten and aggravate infection by high-risk HPV (in particular, by HPV 16) and presents highly suitable conditions for HPV activation, persistence and transformation [43].…”