Archives of Virology

, Volume 162, Issue 9, pp 2855–2860 | Cite as

Genetic diversity of human papillomavirus types 35, 45 and 58 in cervical cancer in Brazil

  • Diogo Lisbôa Basto
  • João Paulo Vidal
  • Valéria Barbosa Pontes
  • Shayany Pinto Felix
  • Laine Celestino Pinto
  • Bruno Moreira Soares
  • Luis Felipe Martins
  • Flávia Miranda Correa
  • Raquel Carvalho Montenegro
  • Cláudia Bessa Pereira Chaves
  • Liz Maria Almeida
  • Miguel Ângelo Martins MoreiraEmail author
Brief Report


In Brazil, most studies of intra-type variants of human papillomavirus (HPV) have focused on HPV16 and HPV18, but other high-risk HPV types have not been studied. Here, we report the prevalence of lineages and variants of HPV35, HPV45 and HPV58 in cervical cancers from the Amazonian and Southeast Brazilian regions. The most frequent sublineages were A1 for HPV35, B2 for HPV45, and A2 for HPV58. The Southeast region had a higher frequency of the B2 sublineage of HPV45, and for HPV35, the genetic and nucleotide sequence diversity were higher in the Southeast region, suggesting that regional factors are influencing the diversity and lineage prevalence.


Cervical cancer Papillomavirus HPV35 HPV45 HPV58 HPV diversity 



We want to thank the physicians who collected the tumor biopsies. This work was supported by the National Institute for Cancer Control (INCT do Cancer:; Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Grants 573806/2008-0, 484005/2013-8 and 305873/2014-8; Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ) Grant E26/170.026/2008; Ministry of Health – Brazil; and Pan-American Health Organization (PAHO).

Compliance with ethical standards

Ethical approval

All procedures were approved by the Research Ethics Committees of the Instituto Nacional de Câncer (CAAE 53398416.0.0000.5274) and the Hospital Ophir Loyola (CAAE 03288212.0.1001.0018).

Informed consent

All patients signed an informed consent form.

Animal rights

This article does not contain any studies with animals.

Conflict of interest

The authors declare no conflict of interest.

Supplementary material

705_2017_3439_MOESM1_ESM.tif (178 kb)
Haplotype network for HPV35 generated by median joining analysis, based on samples of Rio de Janeiro and Pará, medium vectors are indicated by red dots, and the circles in gray (Pará) or black (Rio de Janeiro) are the haplotypes. The diameter of the black and grey circles are proportional to the number of samples sharing a same haplotype (see Table 2) (TIFF 178 kb)
705_2017_3439_MOESM2_ESM.tif (249 kb)
Haplotype network for HPV45 generated by median joining analysis, based on samples of Rio de Janeiro and Pará, medium vectors are indicated by red dots, and the circles in gray (Pará) or black (Rio de Janeiro) are the haplotypes. The diameter of the black and grey circles are proportional to the number of samples sharing a same haplotype (see Table 2) (TIFF 249 kb)
705_2017_3439_MOESM3_ESM.tif (211 kb)
Haplotype network for HPV58 generated by median joining analysis, based on samples of Rio de Janeiro and Pará, medium vectors are indicated by red dots, and the circles in gray (Pará) or black (Rio de Janeiro) are the haplotypes. The diameter of the black and grey circles are proportional to the number of samples sharing a same haplotype (see Table 2) (TIFF 211 kb)
705_2017_3439_MOESM4_ESM.doc (29 kb)
Supplementary material 4 (DOC 29 kb)
705_2017_3439_MOESM5_ESM.xls (110 kb)
Supplementary material 5 (XLS 110 kb)


  1. 1.
    Ferlay J, Soerjomataram I, Dikshit R et al (2015) Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 136:E359–E386. doi: 10.1002/ijc.29210 CrossRefPubMedGoogle Scholar
  2. 2.
    INCA-Instituto Nacional de Câncer José Alencar Gomes da Silva (2015) Coordenação de prevenção e vigilância. Estimativa 2016: Incidência de câncer no Brasil. Instituto Nacional de Câncer José Alencar Gomes da Silva, Rio de Janeiro, pp 1–126Google Scholar
  3. 3.
    Walboomers JMM, Jacobs MV, Manos MM et al (1999) Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J. Pathol. 189:12–19. doi: 10.1002/(SICI)1096-9896(199909)189:1<12:AID-PATH431>3.0.CO;2-F CrossRefPubMedGoogle Scholar
  4. 4.
    Muñoz N, Bosch FX, de Sanjose S  et al (2003) Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med 348:518–527. doi: 10.1056/NEJMoa021641 CrossRefPubMedGoogle Scholar
  5. 5.
    Joura EA, Giuliano AR, Iversen OE et al (2015) A 9-valent HPV vaccine against infection and intraepithelial neoplasia in women. N Engl J Med 372:711–723. doi: 10.1056/NEJMoa1405044 CrossRefPubMedGoogle Scholar
  6. 6.
    Bernard HU, Burk RD, Chen Z et al (2010) Classification of papillomaviruses (PVs) based on 189 PV types and proposal of taxonomic amendments. Virology 401:70–79. doi: 10.1016/j.virol.2010.02.002 CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Burk RD, Harari A, Chen Z (2013) Human papillomavirus genome variants. Virology 445:232–243. doi: 10.1016/j.virol.2013.07.018 CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Berumen J, Ordoñez RM, Lazcano E et al (2001) Asian-American variants of Human Papillomavirus 16 and risk for cervical cancer: a case–control study. J Natl Cancer Inst 93:1325–1330CrossRefPubMedGoogle Scholar
  9. 9.
    Sichero L, Ferreira S, Trottier H et al (2007) High grade cervical lesions are caused preferentially by non-European variants of HPVs 16 and 18. Int J Cancer 120:1763–1768. doi: 10.1002/ijc.22481 CrossRefPubMedGoogle Scholar
  10. 10.
    Zuna RE, Moore WE, Shanesmith RP et al (2009) Association of HPV16 E6 variants with diagnostic severity in cervical cytology samples of 354 women in a US population. Int J Cancer 125:2609–2613. doi: 10.1002/ijc.24706 CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Cornet I, Gheit T, Iannacone MR et al (2013) HPV16 genetic variation and the development of cervical cancer worldwide. Br J Cancer 108:240–244. doi: 10.1038/bjc.2012.508 CrossRefPubMedGoogle Scholar
  12. 12.
    Chen AA, Heideman DAM, Boon D et al (2014) Human papillomavirus 45 genetic variation and cervical cancer risk worldwide. J Virol 88:4514–4521. doi: 10.1128/JVI.03534-13 CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Chan PKS, Zhang C, Park J et al (2013) Geographical distribution and oncogenic risk association of human papillomavirus type 58 E6 and E7 sequence variations. Int J Cancer 132:2528–2536. doi: 10.1002/ijc.27932 CrossRefPubMedGoogle Scholar
  14. 14.
    Junes-Gill K, Sichero L, Maciag PC et al (2008) Human papillomavirus type 16 variants in cervical cancer from an admixtured population in Brazil. J Med Virol 80:1639–1645. doi: 10.1002/jmv.21238 CrossRefPubMedGoogle Scholar
  15. 15.
    Cerqueira DM, Raio T, Véras NM et al (2008) New variants of human papillomavirus type 18 identified in central Brazil. Virus Genes 37:282–287. doi: 10.1007/s11262-008-0263-8 CrossRefPubMedGoogle Scholar
  16. 16.
    Cruz RM, Cerqueira MD, Cruz WB et al (2004) Prevalence of human papillomavirus type 16 variants in the Federal District, Central Brazil. Mem Inst Oswaldo Cruz 99:281–282. doi: 10.1590/S0074-02762004000300007 CrossRefPubMedGoogle Scholar
  17. 17.
    Freitas LB, Chen Z, Muqui EF et al (2014) Human papillomavirus 16 non-European variants are preferentially associated with high-grade cervical lesions. PloS One 9:e10074. doi: 10.1371/journal.pone.0100746 Google Scholar
  18. 18.
    Vidal JPCB, Felix SF, Chaves CBP et al (2016) Genetic diversity of HPV16 and HPV18 in Brazilian patients with invasive cervical cancer. J Med Virol 88:1279–1287. doi: 10.1002/jmv.24458 CrossRefPubMedGoogle Scholar
  19. 19.
    Alves-Silva J, da Silva Santos M, Guimarães PE et al (2000) The ancestry of Brazilian mtDNA lineages. Am J Hum Genet 67:444–461. doi: 10.1086/303004 CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Cornet I, Gheit T, Franceschi S et al (2012) Human papillomavirus type 16 genetic variants: phylogeny and classification based on E6 and LCR. J Virol 86:6855–6861. doi: 10.1128/JVI.00483-12 CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Xi FL, Schiffman M, Koutsky LA et al (2014) Lineages of oncogenic Human Papillomavirus types other than type 16 and 18 and risk for cervical intraepithelial neoplasia. J Natl Cancer Inst 106:dju270. doi: 10.1093/jnci/dju270 CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Pérez S, Cid A, Iñarrea A et al (2014) Prevalence of HPV 16 and HPV 18 lineages in Galicia, Spain. PLoS One 9:e104678. doi: 10.1371/journal.pone.0104678 CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Fuessel Haws AL, He Q, Rady PL et al (2004) Nested PCR with the PGMY09/11 and GP5(+)/6(+) primer sets improves detection of HPV DNA in cervical samples. J Virol Methods 122:87–93. doi: 10.1016/j.jviromet.2004.08.007 CrossRefPubMedGoogle Scholar
  24. 24.
    Almeida LM, Martins LF, Pontes V et al (2017) Human PapilomaVirus (HPV) genotype distribution among cervical cancer patients prior to Brazilian National HPV Immunization Program. J Environ Public Health 2017:1645074. doi: 10.1155/2017/1645074 CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Librado P, Rozas J (2009) DnaSP v5: a software for comprehensive analysis of DNA polymorphism data. Bioinformatics 25:1451–1452. doi: 10.1093/bioinformatics/btp187 CrossRefPubMedGoogle Scholar
  26. 26.
    Tavaré S (1986) Some probabilistic and statistical aspects of the primary structure of nucleotide sequences. In: Miura RM (ed) Lectures on mathematics in the life sciences, vol 17. American Mathematical Society, Providence, pp 57–86Google Scholar
  27. 27.
    Lanave C, Preparata G, Saccone C, Serio G (1984) A new method for calculating evolutionary substitution rates. J Mol Evol 20:86–93CrossRefPubMedGoogle Scholar
  28. 28.
    Guindon S, Dufayard JF, Lefort V et al (2010) New algorithms and methods to estimate maximum-likelihood phylogenies: assessing the performance of PhyMV 3.0. Syst Biol 59:307–321CrossRefPubMedGoogle Scholar
  29. 29.
    Bandelt HJ, Forster P, Röhl A (1999) Median-Joining networks for inferring intraspecific phylogenies. Mol Biol Evol 16:37–48CrossRefPubMedGoogle Scholar
  30. 30.
    Excoffier L, Lischer H (2010) Arlequin suite ver 3.5: a new series of programs to perform population genetics analyses under Linux and Windows. Mol Ecol Res 10:564–567. doi: 10.1111/j.1755-0998.2010.02847.x CrossRefGoogle Scholar
  31. 31.
    Calleja-Macias IE, Villa LL, Prado JC et al (2005) Worldwide genomic diversity of the high-risk human papillomavirus types 31, 35, 52, and 58, four close relatives of human papillomavirus type 16. J Virol 79:13630–13640. doi: 10.1128/JVI.79.21 CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Gauthier B, Coutlée F, Franco EL, Brassard P (2015) Human papillomavirus variants among Inuit women northern Quebec, Canada. Int J Circumpolar Health 74:1–7. doi: 10.3402/ijch.v74.29482 CrossRefGoogle Scholar
  33. 33.
    Calleja-Macias IE, Kalantari M, Huh J et al (2004) Genomic diversity of human papillomavirus-16, 18, 31, and 35 isolates in a Mexican population and relationship to European, African, and Native American variants. Virology 319:315–323. doi: 10.1016/j.virol.2003.11.009 CrossRefPubMedGoogle Scholar
  34. 34.
    Schiffman M, Rodriguez AC, Chen Z et al (2010) A population-based prospective study of carcinogenic human papillomavirus (HPV) variant lineages, viral persistence, and cervical neoplasia. Cancer Res 70:3159–3169. doi: 10.1158/0008-5472.CAN-09-4179 CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Marincevic-Zuniga Y, Gustavsson I, Gyllensten U (2012) Multiply-primed rolling circle amplification of human papillomavirus using sequence-specific primers. Virology 432:57–62. doi: 10.1016/j.virol.2012.05.030 CrossRefPubMedGoogle Scholar
  36. 36.
    Li N, Franceschi S, Howell-Jones MR et al (2011) Human papillomavirus type distribution in 30,848 invasive cervical cancers worldwide: variationby geographical region, histological type and year of publication. Int J Cancer 128:927–935. doi: 10.1002/ijc.25396 CrossRefPubMedGoogle Scholar
  37. 37.
    Chan PKS, Luk AC, Park JS et al (2011) Identification of Human Papillomavirus Type 58 lineages and the distribution worldwide. J Infect Dis 203:1565–1573. doi: 10.1093/infdis/jir157 CrossRefPubMedGoogle Scholar
  38. 38.
    Lopera EA, Baena A, Florez V et al (2014) Unexpected inverse correlation between Native American ancestry and Asian American variants of HPV16 in admixed Colombian cervical cancer cases. Infect Genet Evol 28:339–348. doi: 10.1016/j.meegid.2014.10.014 CrossRefPubMedGoogle Scholar
  39. 39.
    Manta FSN, Pereira R, Vianna R et al (2013) Revisiting the genetic ancestry of Brazilians using autosomal AIM-Indels. PloS One 8:e75145. doi: 10.1371/journal.pone.0075145 CrossRefGoogle Scholar
  40. 40.
    Resque R, Gusmão L, Geppert M et al (2016) Male lineages in Brazil: intercontinental admixture and stratification of the european background. PLoS One 11:e0152573. doi: 10.1371/journal.pone.0152573 CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Austria 2017

Authors and Affiliations

  • Diogo Lisbôa Basto
    • 1
    • 2
  • João Paulo Vidal
    • 2
  • Valéria Barbosa Pontes
    • 3
  • Shayany Pinto Felix
    • 2
  • Laine Celestino Pinto
    • 3
  • Bruno Moreira Soares
    • 3
  • Luis Felipe Martins
    • 4
  • Flávia Miranda Correa
    • 4
  • Raquel Carvalho Montenegro
    • 5
  • Cláudia Bessa Pereira Chaves
    • 6
  • Liz Maria Almeida
    • 4
  • Miguel Ângelo Martins Moreira
    • 2
    Email author
  1. 1.Genetics DepartmentUniversidade Federal do Rio de JaneiroRio de JaneiroBrazil
  2. 2.Genetics ProgramInstituto Nacional de CâncerRio de JaneiroBrazil
  3. 3.Department of Woman Health, Faculty of MedicineUniversidade Federal do ParáBelém do ParáBrazil
  4. 4.Population Research DepartmentInstituto Nacional de Câncer (INCA)Rio de JaneiroBrazil
  5. 5.Department of Physiology and PharmacologyUniversidade Federal do CearáFortalezaBrazil
  6. 6.Gynecologic Section and Molecular Carcinogenesis ProgramInstituto Nacional de CâncerRio de JaneiroBrazil

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