Retrospective Phylodynamic and Phylogeographic Analysis of the Human Papillomavirus 16 E6 Gene in the Mediterranean Region

Abstract

Human papillomavirus 16 (HPV16) is considered to be strongly correlated with the development of cervical cancer. Among the 8 HPV16 genes, the E6 constitutes a remarkable marker to follow the evolutionary history and spatial phylodynamics of HPV16 in the Mediterranean basin. Thus, this work aims to decipher the major evolutionary events and crosstalks in the Mediterranean basin with a focus on Tunisian strains regarding the E6 oncogene. In this study, we first extracted the available and annotated Mediterranean strains of HPV16 E6 gene sequences (n = 155) from the NCBI nucleotide database. These sequences were aligned, edited, and used for the downstream phylogenetic analyses. Finally, a Bayesian Markov Chain Monte Carlo approach was applied to reconstruct the evolutionary history of HPV16 migration. Our results showed that the HPV circulating in Tunisia derived from a Croatian ancestor around the year 1987. This starting point spreads to most European countries to reach northern Africa through the Moroccan gateway in 2004.