Abstract
The incidence of oropharyngeal cancer (OPC) is increasing remarkably among all head and neck cancers, mainly due to its association with the human papillomavirus (HPV). Most HPVs are eliminated by the host’s immune system; however, because HPV has developed an effective immune evasion mechanism to complete its replication cycle, a small number of HPVs are not eliminated, leading to persistent infection. Moreover, during the oncogenic process, the extrachromosomal HPV genome often becomes integrated into the host genome. Integration involves the induction and high expression of E6 and E7, leading to cell cycle activation and increased genomic instability in the host. Therefore, integration is an important event in oncogenesis, although the associated mechanism remains unclear, especially in HPV-OPC. In this review, we summarize the current knowledge on HPV-mediated carcinogenesis, with special emphasis on immune evasion and integration mechanisms, which are crucial for oncogenesis.
Highlights
Role of Immune Evasion and Keywords: human papillomavirus; HPV; HPV-induced oncogenesis; oropharyngeal cancer; immune evasion; viral integration
It has been reported that the cleavage of E1 suppresses the function of downstream E2 and induces local chromosomal instability at the integration site [81,82]. As another factor that can influence E2 expression, Reuschenbach et al reported that the E2 binding site in the long control region (LCR) of HPV-oropharyngeal cancer (OPC) specimens was classified into three groups based on the methylation rate and that in the hypermethylated group, the E2 binding affinity decreased and E6 and
A significant correlation was observed between the methylation levels of HPV16 integrants and that of the flanking host genome. These findings suggest that HPV16 may adopt the methylation status of the flanking host genome in HPV-head and neck squamous cell carcinoma (HNSCC), which may affect the expression of viral genes [67]
Summary
Head and neck cancer (HNC) is the sixth most common cancer, accounting for approximately 3–5% of all cancers, with more than 500,000 diagnoses worldwide every year [1,2]. The leading causes of head and neck squamous cell carcinoma (HNSCC) are smoking and alcohol consumption and viral infections have recently attracted attention as a third factor. HPV infection status is considered an independent prognostic factor for survival in patients with OPC [3]. A small number of HPVs are not eliminated, leading to a persistent infection that eventually develops into HPV-associated carcinoma [12]. In this regard, HPV has likely developed effective immune evasion mechanisms to complete its replication cycle. This review summarizes recent studies on the pathogenic role of HPV-driven carcinogenesis in HNSCC, highlighting HPV-mediated immune evasion systems and viral integration mechanisms
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