Genetic Diversity of Selected High-Risk HPV Types Prevalent in Africa and Not Covered by Current Vaccines: A Pooled Sequence Data Analysis

High-risk human papillomavirus (HR-HPV) types exhibit an uneven global distribution, with types 35, 51, 56, and 59 being more prevalent in Africa yet not covered by current L1-based vaccines. The genetic diversity of HR-HPV oncoproteins in Africa remains poorly characterized, despite their potential as alternative vaccine targets. This study investigates the genetic diversity of HR-HPV types 16, 18, 35, 51, 56, and 59 to inform vaccine development. We analyzed 14,332 sequences from the NCBI Virus database and 222 HPV reference sequences from the Papillomavirus Episteme (PaVE) database using phylogenetic analysis and variant identification. HPV16 and HPV35 exhibited close evolutionary relatedness, which may indicate shared traits relevant to vaccine design, although functional implications remain to be experimentally validated. A key finding of the study was the discovery of novel non-synonymous mutations, including E148K in HPV35 E6, S63C in HPV16 E7 and S495F in HPV18 L1, as well as known oncogenic variants such as L83V (E6) and N29S (E7) in HPV16. These findings highlight significant intra- and inter-type diversity among African HR-HPVs. This study provides new insights into the genetic diversity and evolutionary relationships of underrepresented HR-HPV types. The findings underscore the need for continued genomic surveillance and support efforts to develop region-specific vaccines that include HPV35, 51, 56, and 59 to address gaps in current vaccine coverage and help reduce the burden of HPV-related cancers in Africa.