Esophageal cancer (EC) is an extremely aggressive cancer with one of the highest mortality rates. The cancer is generally only diagnosed at the later stages and has a poor 5-year survival rate due to the limited treatment options. China and South Africa are two countries with a very high prevalence rate of EC. EC rates in South Africa have been on the increase, and esophageal squamous cell carcinoma is the predominant subtype and a primary cause of cancer-related deaths in the black and male mixed ancestry populations in South Africa. The incidence of EC is highest in the Eastern Cape Province, especially in the rural areas such as the Transkei, where the consumption of foods contaminated with Fusarium verticillioides is thought to play a major contributing role to the incidence of EC. China is responsible for almost half of all new cases of EC globally. In China, the prevalence of EC varies greatly. However, the two main areas of high prevalence are the southern Taihang Mountain area (Linxian, Henan Province) and the north Jiangsu area. In both countries, environmental toxins play a major role in increasing the chance that an individual will develop EC. These associative factors include tobacco use, alcohol consumption, nutritional deficiencies and exposure to environmental toxins. However, genetic polymorphisms also play a role in predisposing individuals to EC. These include single-nucleotide polymorphisms that can be found in both protein-coding genes and in non-coding sequences such as miRNAs. The aim of this review is to summarize the contribution of genetic polymorphisms to EC in South Africa and to compare and contrast this to the genetic polymorphisms observed in EC in the most comprehensively studied population group, the Chinese.

Alternative splicing (AS) is a method of increasing the number of proteins that the genome is capable of coding for, by altering the pre-mRNA during its maturation. This process provides the ability of a broad range of proteins to arise from a single gene. AS events are known to occur in up to 94% of human genes. Cumulative data have shown that aberrant AS functionality is a major factor in human diseases. This review focuses on the contribution made by aberrant AS functionality in the development and progression of esophageal cancer. The changes in the pattern of expression of alternately spliced isoforms in esophageal cancer can be used as diagnostic or prognostic biomarkers. Additionally, these can be used as targets for the development of new treatments for esophageal cancer.

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Head and neck cancers include cancers that originate from a variety of locations. These include the mouth, nasal cavity, throat, sinuses, and salivary glands. These cancers are the sixth most diagnosed cancers worldwide. Due to the tissues they arise from, they are collectively named head and neck squamous cell carcinomas (HNSCC). The most important risk factors for head and neck cancers are infection with human papillomavirus (HPV), tobacco use and alcohol consumption. The genetic basis behind the development and progression of HNSCC includes aberrant non-coding RNA levels. However, one of the most important differences between healthy tissue and HNSCC tissue is changes in the alternative splicing of genes that play a vital role in processes that can be described as the hallmarks of cancer. These changes in the expression profile of alternately spliced mRNA give rise to various protein isoforms. These protein isoforms, alternate methylation of proteins, and changes in the transcription of non-coding RNAs (ncRNA) can be used as diagnostic or prognostic markers and as targets for the development of new therapeutic agents. This review aims to describe changes in alternative splicing and ncRNA patterns that contribute to the development and progression of HNSCC. It will also review the use of the changes in gene expression as biomarkers or as the basis for the development of new therapies.

About 15% of all human cancers have a viral etiology. Although progress has been made, understanding the viral oncogenesis and associated molecular mechanisms remain complex. The discovery of cellular miRNAs has led to major breakthroughs. Interestingly, viruses have also been discovered to encode their own miRNAs. These viral, small, non-coding miRNAs are also known as viral-miRNAs (v-miRNAs). Although the function of v-miRNAs largely remains to be elucidated, their role in tumorigenesis cannot be ignored. V-miRNAs have also been shown to exploit the cellular machinery to benefit viral replication and survival. Although the discovery of Hepatitis C virus (HCV), and its viral miRNAs, is a work in progress, the existence of HPV-, EBV-, HBV-, MCPyV- and KSHV-encoded miRNA has been documented. V-miRNAs have been shown to target host factors to advance tumorigenesis, evade and suppress the immune system, and deregulate both the cell cycle and the apoptotic machinery. Although the exact mechanisms of v-miRNAs-induced tumorigenesis are still unclear, v-miRNAs are active role-players in tumorigenesis, viral latency and cell transformation. Furthermore, v-miRNAs can function as posttranscriptional gene regulators of both viral and host genes. Thus, it has been proposed that v-miRNAs may serve as diagnostic biomarkers and therapeutic targets for cancers with a viral etiology. Although significant challenges exist in their clinical application, emerging reports demonstrate their potent role in precision medicine. This review will focus on the roles of HPV-, HCV-, EBV-, HBV-, MCPyV-, and KSHV-produced v-miRNAs in tumorigenesis, as effectors in immune evasion, as diagnostic biomarkers and as novel anti-cancer therapeutic targets. Finally, it will discuss the challenges and opportunities associated with v-miRNAs theranostics in precision oncology.