International Journal of Clinical Case Reports 2024, Vol.14, No.5, 242-252 http://medscipublisher.com/index.php/ijccr 243 the molecular pathways involved in cervical carcinogenesis. This study has the potential to inform public health policies and improve the management and prevention of cervical cancer, ultimately reducing the disease burden globally. 2 Genetic Variability of HPV16/18 in Cervical Cancer 2.1 Types and classification of HPV16/18 variants Human papillomavirus (HPV) types 16 and 18 are the most prevalent high-risk HPV types associated with cervical cancer. These types exhibit significant genetic variability, which can be classified into different lineages and sublineages based on phylogenetic analysis. For HPV16, the major lineages are A, B, C, and D, with further sublineages such as A1, A2, A3, and A4. Similarly, HPV18 is classified into lineages A, B, and C, with sublineages within each major lineage (Vidal et al., 2016). The classification of these variants is typically based on sequencing specific regions of the viral genome, such as the long control region (LCR) and the E6 gene (Guo et al., 2024). For instance, in a study of Brazilian women with invasive cervical cancer, HPV16 variants were predominantly from lineage A, followed by lineages D, B, and C. HPV18 variants were mainly from lineage A, with a smaller proportion from lineage B (Vidal et al., 2016). Another study in Galicia, Spain, found that HPV16 lineage A was the most common, followed by lineages D, B, and C, while HPV18 variants were primarily from lineage A (Pérez et al., 2014). These classifications are crucial as different lineages and sublineages have been associated with varying risks of progression to cervical cancer. For example, the European (EUR) lineage of HPV16, particularly the EUR-350G variant, has been linked to a higher risk of cervical cancer in certain populations (Cornet et al., 2012). Understanding the distribution and classification of these variants helps in identifying populations at higher risk and tailoring preventive measures accordingly. 2.2 Mechanisms of genetic variation in HPV16/18 The genetic variation in HPV16 and HPV18 is driven by several mechanisms, including point mutations, insertions, deletions, and recombination events. One of the key mechanisms is the action of the host's APOBEC3 enzymes, which induce cytosine-to-uracil deamination, leading to mutations in the viral genome. This process has been observed to contribute to the genetic diversity of HPV16, particularly in the non-coding region (NCR) and the E6 gene. Chromosomal integration is another significant mechanism contributing to genetic variation. Integration of HPV DNA into the host genome can lead to disruptions in viral genes and the creation of novel viral-host fusion transcripts. This process is more frequently observed in HPV18 compared to HPV16, with integration events often occurring near cancer-related genes, thereby promoting carcinogenesis (Lagström et al., 2020). Minor nucleotide variations (MNVs) also play a role in the genetic diversity of HPV16 and HPV18. These variations can occur throughout the viral genome and have been associated with different stages of cervical disease. For instance, specific MNVs in the E6 and E7 genes of HPV16 have been linked to higher grades of cervical lesions and increased cancer risk (Zhou et al., 2019). Overall, the genetic variation in HPV16 and HPV18 is a result of complex interactions between viral replication mechanisms and host cellular processes. These variations can influence the virus's ability to evade the immune system, persist in the host, and progress to cancer. 2.3 Prevalence of HPV16/18 variants in different populations The prevalence of HPV16 and HPV18 variants varies significantly across different geographical regions and populations. Studies have shown that certain lineages and sublineages are more common in specific regions, which can influence the local epidemiology of cervical cancer. In a multicenter study involving samples from Europe, Central Asia, and South/Central America, the distribution of HPV16 variants showed notable differences. In Europe and Central Asia, the EUR-350G variant was underrepresented in cervical cancer cases, while in South/Central America, it was overrepresented, indicating a population-dependent risk associated with this variant (Cornet et al., 2012). Similarly, HPV18 variants also showed regional differences, with lineages B and C being more prevalent in Africa, while lineage A was more common in other regions (Chen et al., 2014).
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