CONICET | Buscador de Institutos y Recursos Humanos

Human papillomavirus (HPV)16 is the most oncogenic human papillomavirus,responsible for most papillomavirus-inducedanogenital cancers. We have exploredby sequencing and phylogenetic analysis the viral variant lineages presentin 692 HPV16-monoinfectedinvasive anogenital cancers from Europe, Asia,and Central/South America. We have assessed the contribution of geographyand anatomy to the differential prevalence of HPV16 variants and to the nonsynonymousE6 T350G polymorphism. Most (68%) of the variance in the distributionof HPV16 variants was accounted for by the differential abundanceof the different viral lineages. The most prevalent variant (above 70% prevalence)in all regions and in all locations was HPV16_A1-3,except in Asia, whereHPV16_A4 predominated in anal cancers. The differential prevalence of variantsas a function of geographical origin explained 9% of the variance, and thedifferential prevalence of variants as a function of anatomical location accountedfor less than 3% of the variance. Despite containing similar repertoires of HPV16variants, we confirm the worldwide trend of cervical cancers being diagnosedsignificantly earlier than other anogenital cancers (early fifties vs. early sixties).Frequencies for alleles in the HPV16 E6 T350G polymorphism were similaracross anogenital cancers from the same geographical origin. Interestingly, anogenitalcancers from Central/South America displayed higher 350G allele frequenciesalso within HPV16_A1-3lineage compared with Europe. Our resultsdemonstrate ample variation in HPV16 variants prevalence in anogenital cancers,which is partly explained by the geographical origin of the sample and onlymarginally explained by the anatomical location of the lesion, suggesting thattissue specialization is not essential evolutionary forces shaping HPV16 diversityin anogenital cancers.