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We have explored by sequencing and phylogenetic analysis the viral variant lineages present in 692 <jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content>16\u2010monoinfected invasive anogenital cancers from Europe, Asia, and Central\/South America. We have assessed the contribution of geography and anatomy to the differential prevalence of <jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content>16 variants and to the nonsynonymous <jats:italic>E6<\/jats:italic> T350G polymorphism. Most (68%) of the variance in the distribution of <jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content>16 variants was accounted for by the differential abundance of the different viral lineages. The most prevalent variant (above 70% prevalence) in all regions and in all locations was <jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content>16_A1\u20103, except in Asia, where <jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content>16_A4 predominated in anal cancers. The differential prevalence of variants as a function of geographical origin explained 9% of the variance, and the differential prevalence of variants as a function of anatomical location accounted for less than 3% of the variance. Despite containing similar repertoires of <jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content>16 variants, we confirm the worldwide trend of cervical cancers being diagnosed significantly earlier than other anogenital cancers (early fifties vs. early sixties). Frequencies for alleles in the <jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content>16 <jats:italic>E6<\/jats:italic> T350G polymorphism were similar across anogenital cancers from the same geographical origin. Interestingly, anogenital cancers from Central\/South America displayed higher 350G allele frequencies also within <jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content>16_A1\u20103 lineage compared with Europe. Our results demonstrate ample variation in <jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content>16 variants prevalence in anogenital cancers, which is partly explained by the geographical origin of the sample and only marginally explained by the anatomical location of the lesion, suggesting that tissue specialization is not essential evolutionary forces shaping <jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content>16 diversity in anogenital cancers.<\/jats:p>","DOI":"10.1002\/cam4.870","type":"journal-article","created":{"date-parts":[[2016,9,22]],"date-time":"2016-09-22T04:12:48Z","timestamp":1474517568000},"page":"2909-2919","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["HPV16 variants distribution in invasive cancers of the cervix, vulva, vagina, penis, and 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