Abstract
Human Papillomavirus Type 59 (HPV-59) is a high-risk subtype linked to cervical and other cancers. However, its codon usage patterns remain underexplored despite their importance in understanding viral behavior and vaccine optimization. This study reveals a mild codon usage bias in HPV-59, with a notable preference for A/T-ending codons and 29 favored codons, primarily ending in A or T. Additionally, CpG dinucleotides were significantly underrepresented, potentially aiding immune evasion. Analyses using the Parity Rule 2, Effective Number of Codons plot, and neutrality plot indicate that both mutational pressure and natural selection shape codon usage, with natural selection playing a dominant role. The virus's codon usage moderately aligns with human translational machinery, as shown by the Isoacceptor tRNA pool, Codon Adaptation Index, and Relative Codon Deoptimization Index, reflecting an evolutionary balance between protein synthesis efficiency and host compatibility. These findings provide valuable insights into HPV-59 biology, offering guidance for developing optimized vaccines.