title: HPV16 variants distribution in invasive cancers of the cervix, vulva, vagina, penis, and anus.
abstract: Human papillomavirus (HPV)16 is the most oncogenic human papillomavirus, responsible for most papillomavirus-induced anogenital cancers. We have explored by sequencing and phylogenetic analysis the viral variant lineages present in 692 HPV16-monoinfected invasive anogenital cancers from Europe, Asia, and Central/South America. We have assessed the contribution of geography and anatomy to the differential prevalence of HPV16 variants and to the nonsynonymous E6 T350G polymorphism. Most (68%) of the variance in the distribution of HPV16 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 HPV16_A1-3, except in Asia, where HPV16_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 HPV16 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 HPV16 E6 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 HPV16_A1-3 lineage compared with Europe. Our results demonstrate ample variation in HPV16 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 HPV16 diversity in anogenital cancers.
authors.affiliation: Infections and Cancer Unit, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO), Barcelona, Spain.|Bellvitge Institute of Biomedical Research (IDIBELL), Barcelona, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Nicolás-Párraga
authors.affiliation: Infections and Cancer Unit, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO), Barcelona, Spain.|Bellvitge Institute of Biomedical Research (IDIBELL), Barcelona, Spain.
authors.forename: Carolina
authors.initials: C
authors.lastname: Gandini
authors.affiliation: Infections and Cancer Unit, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO), Barcelona, Spain.|Bellvitge Institute of Biomedical Research (IDIBELL), Barcelona, Spain.
authors.forename: Ville N
authors.initials: VN
authors.lastname: Pimenoff
authors.affiliation: Infections and Cancer Unit, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO), Barcelona, Spain.|Bellvitge Institute of Biomedical Research (IDIBELL), Barcelona, Spain.
authors.forename: Laia
authors.initials: L
authors.lastname: Alemany
authors.affiliation: Infections and Cancer Unit, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO), Barcelona, Spain.|Bellvitge Institute of Biomedical Research (IDIBELL), Barcelona, Spain.|CIBER in Epidemiology and Public Health (CIBERESP), Barcelona, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: de Sanjosé
authors.affiliation: Infections and Cancer Unit, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO), Barcelona, Spain.|Bellvitge Institute of Biomedical Research (IDIBELL), Barcelona, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Xavier Bosch
authors.affiliation: Infections and Cancer Unit, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO), Barcelona, Spain. ignacio.bravo@ird.fr.|MIVEGEC, National Center for Scientific Research (CNRS), Montpellier, France. ignacio.bravo@ird.fr.
authors.forename: Ignacio G
authors.initials: IG
authors.lastname: Bravo
mesh_terms: D001005:Anus Neoplasms / Q000821:virology*; D001208:Asia / Q000453:epidemiology; D002489:Central America / Q000453:epidemiology; D005060:Europe / Q000453:epidemiology; D005260:Female; D006801:Humans; D008297:Male; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D027383:Papillomaviridae / Q000145:classification* / Q000235:genetics; D030361:Papillomavirus Infections / Q000150:complications / Q000453:epidemiology; D010412:Penile Neoplasms / Q000821:virology*; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D012097:Repressor Proteins / Q000235:genetics*; D013020:South America / Q000453:epidemiology; D002583:Uterine Cervical Neoplasms / Q000821:virology*; D014625:Vaginal Neoplasms / Q000821:virology*; D014846:Vulvar Neoplasms / Q000821:virology*
chemical_list: C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins
keywords: Anogenital cancers; papillomavirus infection and cancer; viral diversity; viral evolution; virus-host interactions