Tracing the evolutionary history of Tunisian HPV 16 and 18 across the genetic diversity in L1 gene

Abstract

HPV16 and HPV18 are the most prevalent high risk HPV types, recognized to be HPV vaccine target. Currently, available vaccines against HPV infections are based on virus-like particles (VLPs) derived from the L1 protein. Understanding the emergence of HPV isolates and exploring the genetic diversity of their L1 gene is crucial to assess the effectiveness of vaccine introduction in different populations. This is the first study aiming to investigate the evolutionary dynamics of HPV16 and HPV18 variants circulating in Tunisia. We constructed evolutionary history of HPV16 and HPV18 based on partial L1 sequence dataset of 733 Tunisian and worldwide representative isolates. Phylogeographic analysis confirmed the European origin of Tunisian strains that have emerged in 90's. Strikingly, four nonsense mutations in HPV16 and one in HPV18 within the HI surface loop, a critical immunogenic region were identified. Moreover, the latter showed an excess of non-synonymous over synonymous substitutions, a hallmark of local adaptation. By elucidating the genetic variability in the L1 gene, our study unveils several new features that pose challenges to the ongoing fight against HPV. These insights underscore the importance of continuous surveillance and adaptation of vaccination strategies to address evolving viral dynamics effectively.