![]() According to the global cancer report in 2021, about 600,000 cancer cases worldwide are reported to be associated with high-risk HPV infections, causing 340,000 deaths. Depending on the association of HPV subtypes with cancer progression, they are divided into high-risk HPVs and low-risk HPVs ( Zheng and Baker, 2006 Stanley, 2008).Ībout 15% of human cancers are caused by a viral infection a high-risk HPV infection nearly accounts for half of all cases. However, it will develop into a persistent infection in some rare cases, further developing into malignant lesions and progressing to cancer if left untreated ( Parkin and Bray, 2006 Zheng and Baker, 2006). In most cases, a HPV infection is usually asymptomatic and will disappear within 2 years ( Richardson et al., 2003). As one of the most common sexually transmitted diseases among almost all sexually active populations, a HPV-caused viral infection usually starts at the cutaneous or mucosal epithelium at the basal layer through sexual activity or a small wound. The genome size of HPVs consists of 8,000 nucleotides ( zur Hausen, 2002 zur Hausen, 2009). Human papillomaviruses (HPV) are non-enveloped, small, double-stranded DNA viruses. Human Papillomavirus Infection and Related Cancers Finally, we also reviewed the role of various splicing factors in the regulation of high-risk HPV oncogenic E6/E7 mRNA splicing. In this review, we concluded the relationship of different E6/E7 transcripts with cancer progression, the known splicing sites, and the identified cis-regulatory elements within high-risk HPV E6/E7-coding region. Therefore, it is crucial to understand the regulation of E6/E7 splice site selection and the interaction of splicing enhancers and silencers with cellular splicing factors. Interrupting the balance of E6 and E7 levels results in cell apoptosis. Hence, the alternative splicing in the E6/E7-coding region affects the balance of the E6/E7 expression level. The oncogenic viral proteins expressed by high-risk HPVs E6/E7 are tightly involved in cell proliferation, differentiation, and cancerous transformation since E6/E7 mRNAs are derived from the same pre-mRNA. The most common high-risk subtypes are HPV16 and HPV18. High-risk human papillomavirus infection may develop into a persistent infection that is highly related to the progression of various cancers, including cervical cancer and head and neck squamous cell carcinomas. 2School of Biomedical Engineering, Dalian University of Technology, Dalian, China. ![]()
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