Maya Savira

Detecting Human Papillomavirus Type 16 in Cervical Cancer Patients with Molecular Variation of Gene L1 in Riau Province Indonesia

Cervical cancer is the second most deadly cancer in the world after breast cancer. The cancer is caused by infection of high risk Human Papillomavirus (HPV) type 16. It is often found in cervical cancer of which the genome structure is composed of L1 proteins. The L1 protein makes up the viral capsid that has an important role in causing the cervical epithelium. Several studies have found the differences in HPV nucleotides variants that lead to changes in amino acids that disrupt the structure, the natural function of the virus itself, and ultimately lead to changes in biological functions including host immunological recognition. Variation of the L1 gene also affects the effectiveness of existing vaccines. This research was a descriptive study conducted at the laboratory of microbiology, the Faculty of Medicine, Universitas Riau, Pekanbaru from February to August 2018. The study was aimed at looking at the molecular variations of the L1 HPV type 16 gene and examining phylogenic kinship. The SNPs (Single Nucleotide Polymorphism) which occurred in 26 sample isolates are the substitution of C/G (6240), A/G (6432), T/G (6686), C/T (6824). These variations also cause changes in amino acids, insertion of ATC nucleotide bases (6902), and deletions of GAT bases (6954). There are  molecular variations of the L1 HPV type 16 gene which can cause different host immune responses. Phylogenic kinship of HPV type 16 isolate in Riau is similar to  Asian-American isolate.

Genetic variations of the L2 gene in human papillomavirus (HPV) type 16 from cervical cancer patients in Sumatra region, Indonesia

The L2 protein, a minor capsid component of human papillomavirus (HPV), plays a critical role in the HPV life cycle by packaging the viral genome with the L1 protein and facilitating DNA transport to the nucleus. Identifying genetic variations in the L2 gene is essential for improving vaccine development, diagnostic accuracy, and understanding viral evolution, potentially contributing to more effective HPV vaccines. The aim of this study was to investigate the genetic variation of the L2 gene in cervical cancer specimens collected from patients in Riau Province, Indonesia. A single-center, cross-sectional study was conducted at Arifin Achmad General Hospital, Riau Province, involving cervical cancer patients with confirmed HPV16 infection between January 2018 and August 2020. Demographic, clinical, and risk factor data were collected through structured interviews and direct assessments. Cervical biopsy specimens were collected, and viral DNA was extracted for L2 gene amplification using polymerase chain reaction (PCR). Sequencing was conducted on PCR products, followed by single-nucleotide polymorphism (SNP) identification through alignment with the HPV16 reference genome. The amplification and sequencing of the HPV16 L2 gene from 22 cervical cancer specimens revealed 36 SNPs, including 31 nonsynonymous and five synonymous mutations. High-frequency mutations were observed at nucleotide positions 4,074 and 4,177, each detected in 95.45% of the samples. Notable insertions were found at positions 3,668–3,669 and 4,275–4,276, indicating substantial sequence variation. Phylogenetic analysis grouped the sequences into three clusters, with most belonging to sub-lineage A2 (European), while others aligned with A4 (Asian) and East Asian lineages. The observed genetic diversity in the HPV16 L2 gene may reflect regional viral evolution and has potential implications for future vaccine development.

Promising candidate drug target genes for repurposing in cervical cancer: A bioinformatics-based approach

Cervical cancer is the fourth most common cancer among women globally, and studies have shown that genetic variants play a significant role in its development. A variety of germline and somatic mutations are associated with cervical cancer. However, genomic data derived from these mutations have not been extensively utilized for the development of repurposed drugs for cervical cancer. The objective of this study was to identify novel potential drugs that could be repurposed for cervical cancer treatment through a bioinformatics approach. A comprehensive genomic and bioinformatics database integration strategy was employed to identify potential drug target genes for cervical cancer. Using the GWAS and PheWAS databases, a total of 232 genes associated with cervical cancer were identified. These pharmacological target genes were further refined by applying a biological threshold of six functional annotations. The drug target genes were then cross-referenced with cancer treatment candidates using the DrugBank database. Among the identified genes, LTA, TNFRSF1A, PRKCZ, PDE4B, and PARP were highlighted as promising targets for repurposed drugs. Notably, these five target genes overlapped with 12 drugs that could potentially be repurposed for cervical cancer treatment. Among these, talazoparib, a potent PARP inhibitor, emerged as a particularly promising candidate. Talazoparib is currently being investigated for safety and tolerability in other cancers but has not yet been studied in the context of cervical cancer. Further clinical trials are necessary to validate this finding and explore its potential as a repurposed drug for cervical cancer.