HPV16 L1 diversity and its potential impact on the vaccination-induced immunity

Abstract

Human Papillomavirus 16 (HPV16) is the most oncogenic HPV and the most associated genotype with cervical cancer development and progression. Currently, all developed vaccines are targeting HPV16 and were designed based on the major L1 capsid protein. Thus, evaluation of the diversity of HPV16 L1 sequence, mainly in the antigenic regions, will be of a great interest to assess the efficacy of the prophylactic vaccines and to predict the impact of genetic variations in these regions on the vaccination-induced immunity. A total of 377 HPV16 L1 sequences, published in public domain GenBank database, from the Americas, Africa, Asia, and Europe were collected and assembled.A total of 626 mutation events affecting 83 distinct nucleotides into the five antigenic regions of L1 gene of HPV16 were reported, and most SNPs were located in DE (27.38%, 23/83) and FG (31%, 26/83) loops. Overall, 4 mutations were frequently found in HPV16 sequences: T176N and N181T in EF loop; A266T in the FG loop and T353P/I/N HI loop. Of particular interest, some SNPs are ubiquitous and were found in all populations whereas others were population specific and their presence was limited to one or 2 at the maximum.Association between mutations in the antigenic regions and ethnicity was also investigated and showed that mutations in BC and DE loops were present with no significant difference in sequences from Europe, Asia, America and Africa. However, most mutations in FG loop are reported in sequences from European cases and are less pronounced in cases from America and Asia, whereas mutations EF and HI loops prevail in Asian cases.These data highlight a high number of variant amino acid residues that could affect the vaccination-induced immunity and impact the effectiveness of the prophylactic vaccination to fight against HPV, warranting the need of further investigation for vaccines and natural history studies of HPV16.