Skip to main content

Identification of high-risk human papillomavirus isolates circulating in Nigeria and phylogenetic analysis based on the virus essential protein

Abstract

Purpose

Human papillomavirus detection is crucial in determining preventive approach in cervical cancer. Different HPV genotypes have been reported worldwide and have shown variations with respect to geographic location and oncogenic capabilities. We aimed to conduct molecular characterization and phylogenetic analysis of human papillomavirus (HPV) in Northern Nigeria, to guide public health intervention.

Methods

Cervical smear samples were collected from 148 consenting subjects attending different Hospitals in Northern Nigeria. It was stained with Papanicolaou method and processed for molecular detection of HPV. Isolates of HPV were sequenced targeting HPVL1 gene. The sequences were analysed for single-nucleotide polymorphism. HPV variant lineages and relatedness was determined by phylogenetic analysis.

Results

The result of the present study showed that 26.4% (34) of the subjects had HPV infection. The result of the cytodiagnosis showed that 29.4% (10/34) had normal cytology, 23.5% (8/34) had ASCUS, and 20.6% (7/34) had LSIL, while those having HSIL and SCC accounts for 20.6% (7/34) and 5.9% (2/34), respectively. The result for sequence analysis shows about fifteen different circulating genotypes in Northern Nigeria. Out of these, HPV 16 has the highest frequency (20.6%), while HPV 11, 70, 18, 31, 33, 35, 52, 56 and 7 has the least frequency (2.9%) each. Total of 21 single-nucleotide polymorphisms were detected, out of which 15 are synonymous, while 6 are non-synonymous mutations. Phylogenetic analysis of HPV genotypes using maximum likelihood method showed that majority of HPV genotypes from Nigeria clustered with two undetermined lineages. Pairwise distance estimation of some sequences from this study and some reference sequence revealed a distance ranging from 0.0082 to 2.0994, indicating that the sequences are majorly closely related.

Conclusion

The present study provided important data about molecular epidemiology, characteristics, phylogeny and polymorphism which will aid in further studies that will advance in-depth understanding of the viral molecular epidemiology and possibly policy on public health intervention.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2

Data Availability

All data and information regarding this manuscript will be made available on request.

Abbreviations

HPV:

Human papillomavirus

HR-HPV:

High-risk human papillomavirus

LR-HPV:

Low-risk human papillomavirus

SNP:

Single-nucleotide polymorphism

ASCUS:

Atypical squamous cells of undetermined significance

LSIL:

Low-grade squamous intraepithelial lesion

HSIL:

High-grade squamous intraepithelial lesion

PCR:

Polymerase chain reaction

References

  1. 1.

    Arbyn M, Weiderpass E, Bruni L, de Sanjosé S, Saraiya M, Ferlay J, Bray F. Estimates of incidence and mortality of cervical cancer in 2018: a worldwide analysis. The Lancet Global Health. 2020. https://doi.org/10.1016/S2214-109X(19)30482-6.

    Article  PubMed  Google Scholar 

  2. 2.

    Smith JS, Lindsay L, Hoots B, Keys J, Francheschi S, Winer R, Clifford GM. Human papillomavirus type distribution in invasive cervical cancer and high-grade cervical lesions: a meta-analysis update. Int J Cancer. 2007;121:621–32.

    CAS  Article  Google Scholar 

  3. 3.

    Burd EM. Human papillomavirus and cervical cancer. Clin Microbiol Rev. 2003;16(1):1–17.

    CAS  Article  Google Scholar 

  4. 4.

    Bosch FX, de Sanjosé S, Castellsagué X. HPV and genital cancer: the essential epidemiology. Vacc Prev Cerv Cancer. 2008;12:18–22.

    Google Scholar 

  5. 5.

    Stanley MA. Pathology and epidemiology of HPV infection in females. Gynecol Oncol. 2010;117(2):5–10.

    Article  Google Scholar 

  6. 6.

    Bedoya-Pilozo CH, Medina Magues LG, Espinoga-Garcia M, Sanches M, Parrales Valdiviezo JV, Molina D, Badano I. Molecular epidemiology and phylogenetic analysis of human papillomavirus infection in women with cervical lesions and cancer from the coastal region of Ecuador. Rev Argent Microbiol. 2017;50(2):136–46.

    PubMed  Google Scholar 

  7. 7.

    Marth GT, Korl I, Yandell MD, Yeh RT, Gu Z, Zakeri H, Gish WR. A general approach to single-nucleotide polymorphism discovery. Nat Genet. 1999;23(4):452–6.

    CAS  Article  Google Scholar 

  8. 8.

    Thomas JO, Herrero R, Omigbodun AA, Ojemakinde K, Ajayi IO, Fawole A, Franceschi S. Prevalence of papillomavirus infection in women in Ibadan, Nigeria: a population-based study. Br J Cancer. 2004;90(3):638–45.

    CAS  Article  Google Scholar 

  9. 9.

    Manga MM, Fowotade A, Abdullahi YM, El-nafaty AU, Adamu DB, Pindiga HU, Osoba AO. Epidemiological patterns of cervical human papillomavirus infection among women presenting for cervical cancer screening in North-Eastern Nigeria. Infect Agent Cancer. 2015;10:39.

    Article  Google Scholar 

  10. 10.

    Auwal IK, Aminu M, Atanda AT, Tukur J, Sarkinfada F. Prevalence and risk factors of high risk human papillomavirus infections among women attending gynaecology clinics in Kano. Northern Nigeria Bajopas. 2014;6:67–71.

    Google Scholar 

  11. 11.

    Dareng EO, Ma B, Famooto AO, Akarolo-Anthony SN, Offiong RA, Olaniyan O, Adebamowo CA. Prevalent high-risk HPV infection and vaginal microbiota in Nigerian women. Epidemiol infect. 2016;2016(144):123–37.

    Article  Google Scholar 

  12. 12.

    Papanicolaou GN. A new procedure for staining vaginal smears. Science. 1942;95(2469):438–9.

    CAS  Article  Google Scholar 

  13. 13.

    Bernard HU, Chan SY, Manos MM, Ong CK, Villa LL, Delius H, Wheeler M. Identification and assessment of known and novel human papillomaviruses by polymerase chain reaction amplification, restriction fragment length polymorphisms, nucleotide sequence, and phylogenetic algorithms. J Infect Dis. 1994;170(5):1077–85.

    CAS  Article  Google Scholar 

  14. 14.

    Tamura K, Nei M. Estimation of the number of nucleotide substitutions in the control region of mitochondrial DNA in humans and chimpanzees. Mol Biol Evol. 1993;10:512–26.

    CAS  PubMed  Google Scholar 

  15. 15.

    Kumar S, Stecher G, Tamura K. MEGAX: Molecular Evolutionary Genetics Analysis version X for bigger datasets. Mol Biol Evol. 2016;33:1870–4.

    CAS  Article  Google Scholar 

  16. 16.

    Nayar R, Wilbur DC. The pap test and Bethesda 2014. Acta Cytol. 2015;59(2):121–32.

    CAS  Article  Google Scholar 

  17. 17.

    Jing Y, Wang T, Chen Z, Ding X, Xu J, Mu X, Cao M, Chen H. Phylogeny and Polymorphism in the long control regions E6, E7, and L1 of HPV Type 56 in women from Southwest China. Mol Med Rep. 2008;17:7131–41.

    Google Scholar 

  18. 18.

    Fadahunsi OO, Omoniyi-Esan GO, Banjo AAF, Esimai OA, Osiagwu D, Clement F, Iyola S. Prevalence of high risk oncogenic human papillomavirus types in cervical smears of women attending well woman clinic in Ile Ife Nigeria. Gynecol Obst. 2013. https://doi.org/10.4172/2161-0932.1000185.

    Article  Google Scholar 

  19. 19.

    Gage JC, Ajenifuja KO, Wentzensen NA, Adepiti AC, Eklund C, Reilly M, Schiffman M. The age-specific prevalence of human papillomavirus and risk of cytologic abnormalities in rural Nigeria: Implications for screen-and-treat strategies. Int J Cancer. 2012;130(9):2111–7.

    CAS  Article  Google Scholar 

  20. 20.

    Kleter BL, van Doorn J, Schrauwen L, Molijn A, Sastrowijoto S, Terschegget J, Quint M. Development and clinical evaluation of a highly sensitive PCR-reverse hybridization line probe assay for detection of anogenital human papillomavirus. J Clin Microbiol. 1999;37(8):2508–17.

    CAS  Article  Google Scholar 

  21. 21.

    De Sanjosé S, Diaz M, Castellsagué X, Clifford G, Bruni L, Munoz L, Bosch FX. Worldwide prevalence and genotype distribution of cervical human papillomavirus DNA in women with normal cytology: a meta-analysis. Lancet. 2007;7(7):453–9.

    Article  Google Scholar 

  22. 22.

    Badial RM, Dias MC, Stuqui B, Melli P, Quintana SM, Bonfim C, Rahal P. Detection and genotyping of human papillomavirus (HPV) in HIV-infected women and its relationship with HPV/HIV co-infection. Medicine. 2018;97(14):e9545.

    Article  Google Scholar 

  23. 23.

    Aliyu IA, Ling KL, Md Hashim NF, Chee HY. Annexin A2 Translocation and Virus Interaction; a Potential Target for Antivirus Drug Discovery. Rev Med Virol. 2019. https://doi.org/10.1002/rmv.2038.

    Article  PubMed  Google Scholar 

  24. 24.

    Ghedira R, Mahfoudh W, Hadhri S, Gabbouj S, Bouanene I, Khairi H, Hassen E. Human papillomavirus genotypes and HPV-16 variants distribution among Tunisian women with normal cytology and squamous intraepithelial lesions. Infect Agent Cancer. 2016;11:61.

    CAS  Article  Google Scholar 

Download references

Acknowledgements

The authors gratefully acknowledge MLS. Sani Aliyu Mohammed, Dr. Yusuf M. Abdullahi, Dr. Aliyu Ibrahim Lawan and Dr. Aliyu Bala Umar for their useful contributions towards this research.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors.

Author information

Affiliations

Authors

Contributions

KI, DU and AIA presented the methods, carryout the experiment, analysed the data and wrote the manuscript, KI, KA, BJ and AIA, conceptualized the work, supervised and approved the manuscript, and KI, YL, BH, AS, DA, NL and AU, performed laboratory work. All authors approved the manuscript as submitted.

Corresponding author

Correspondence to Aliyu Isah Abubakar.

Ethics declarations

Conflict of interest

The authors declared that they have no conflict of interest.

Ethics Approval

Ethical approval was obtained from the research and ethics committee of the hospitals from which the study subjects were recruited.

Informed Consent

Samples were collected from consenting individuals.

Consent for Publication

Consent to publish findings was obtained from the study subjects.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Malik, K.I., Aliyu, D.U., Abubakar, B.J. et al. Identification of high-risk human papillomavirus isolates circulating in Nigeria and phylogenetic analysis based on the virus essential protein. Indian J Gynecol Oncolog 19, 87 (2021). https://doi.org/10.1007/s40944-021-00587-9

Download citation

Keywords

  • Human papillomavirus
  • Single-nucleotide polymorphism
  • Phylogenetic analysis
  • Cervical cancer