The Catastrophic HPV/HIV Dual Viral Oncogenomics in Concert with Dysregulated Alternative Splicing in Cervical Cancer

Abstract

Cervical cancer is a public health problem and has devastating effects in low-to-middle-income countries (LTMICs) such as the sub-Saharan African (SSA) countries. Infection by the human papillomavirus (HPV) is the main cause of cervical cancer. HIV positive women have higher HPV prevalence and cervical cancer incidence than their HIV negative counterparts do. Concurrent HPV/HIV infection is catastrophic, particularly to African women due to the high prevalence of HIV infections. Although various studies show a relationship between HPV, HIV and cervical cancer, there is still a gap in the knowledge concerning the precise nature of this tripartite association. Firstly, most studies show the relationship between HPV and cervical cancer at genomic and epigenetic levels, while the transcriptomic landscape of this relationship remains to be elucidated. Even though many studies have shown HPV/HIV dual viral pathogenesis, the dual molecular oncoviral effects on the development of cervical cancer remains largely uncertain. Furthermore, the effect of highly active antiretroviral therapy (HAART) on the cellular splicing machinery is unclear. Emerging evidence indicates the vital role played by host splicing events in both HPV and HIV infection in the development and progression to cervical cancer. Therefore, decoding the transcriptome landscape of this tripartite relationship holds promising therapeutic potential. This review will focus on the link between cellular splicing machinery, HPV, HIV infection and the aberrant alternative splicing events that take place in HIV/HPV-associated cervical cancer. Finally, we will investigate how these aberrant splicing events can be targeted for the development of new therapeutic strategies against HPV/HIV-associated cervical cancer.

Analysis of Distributions of HPV Infection in Females with Cervical Lesions in the Western District of Beijing Chaoyang Hospital

“…The number of new cases of cervical cancer in China is increasing at a rate of 15,000 per year, ranking the second in the world [ 2 ]. Human papilloma virus (HPV) infection is a high-risk factor leading to cervical cancer, which seriously affects women's physical and mental health and reproductive outcomes [ 3 ]. The occurrence of cervical squamous intraepithelial lesion (SIL) and cervical cancer is mainly related to the persistent high-risk HPV infection.…”

Everolimus (RAD001) combined with programmed death-1 (PD-1) blockade enhances radiosensitivity of cervical cancer and programmed death-ligand 1 (PD-L1) expression by blocking the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR)/S6 kinase 1 (S6K1) pathway

“…There are more than 90% of deaths in low and middle-income countries [ 5 ]. CC is attributed to diverse risk factors, such as drinking, smoking, unprotected sex, multiple sexual partners, extended use of oral contraceptives, a family history of CC, socioeconomic status, and virus infections [ 6 ]. Moreover, nearly all CC cases are caused by human papillomavirus [ 7 ].…”

LncRNA LAMTOR5‐AS1 sponges miR‐210‐3p and regulates cervical cancer progression

“…Global data show that the average age of onset of new cervical cancer patients is decreasing and the patients are getting younger 7 . However, postoperative recurrence and poor prognosis still exist in patients with cervical cancer 8,9 . Based on this, finding new therapeutic and prognostic markers can prolong the survival of patients and provide more effective treatment for patients.…”