A Technical Comparison of Human Papillomavirus Genotyping Assays from a Population-Based Cervical Cancer Screening in South Central Ethiopia

Brhanu Teka, Muluken Gizaw, Ededia Firdawoke, Adamu Addissie, Tesfamichael Awoke Sisay, Carola Schreckenberger, Anna Sophie Skof, Sarah Thies, Adane Mihret, Eva Johanna Kantelhardt, Tamrat Abebe, Andreas M Kaufmann, Brhanu Teka, Muluken Gizaw, Ededia Firdawoke, Adamu Addissie, Tesfamichael Awoke Sisay, Carola Schreckenberger, Anna Sophie Skof, Sarah Thies, Adane Mihret, Eva Johanna Kantelhardt, Tamrat Abebe, Andreas M Kaufmann

Abstract

Purpose: High-risk Human Papillomavirus (HPV) is the most important cause of cervical cancer. The highest burden of disease is seen in Low- and Low-Middle-Income Countries (LMIC). Several new HPV screening assays have been developed for high-risk HPV (hr-HPV) testing. We compared the performance and adequacy of three HPV genotyping assays on samples from a population of rural women in south-central Ethiopia.

Patients and methods: One hundred and ten cervical swabs from rural women screened for HPV were assayed. HPV DNA was tested using MPG-Luminex Assay, Anyplex II HPV HR Detection, and EUROArray HPV. MPG-Luminex Assay was used as a reference method to compute the sensitivity and specificity of the two commercial assays in detecting hr-HPV infections.

Results: Of the 110 samples, MPG-Luminex Assay found 18.2% positive for the 14 hr-HPV and 7.3% for the probable hr-HPV genotypes. Anyplex™ II HPV HR Detection assay and EUROArray HPV Assay identified 21.82% and 12.7% samples, respectively, for the 14 hr-HPVs and both 7.3% for the probable hr-HPV genotypes (κ=0.734). Among the 14 hr-HPV genotypes, the genotype-specific agreement of the three HPV genotyping assays was moderate or better for HPV16, 31, 35, 39, 52, 56, 66 and 68. The aggregated sensitivity in detecting the 14 hr-HPV infections of Anyplex™ II HPV HR Detection and EUROArray HPV assays was high, 100% and 70%, respectively. The specificities of Anyplex™ II HPV HR Detection and EUROArray HPV were 95.6% and 100%, respectively.

Conclusion: The three evaluated assays showed similar analytical performance in the detection of hr-HPV infections and moderate or better concordance in HPV genotyping. This study is part of the ongoing cluster-randomized trial that has been registered in clinicaltrials.gov (NCT03281135) on September 13, 2017.

Keywords: HPV PCR test accuracy; HPV test complexity; HPV testing; LMIC; analytical performance.

Conflict of interest statement

The authors declare that they have no conflicts of interest in relation to this work.

© 2022 Teka et al.

References

    1. World Health Organization - International Agency for Research on Cancer. Globocan 2020 - Cervix uteri; 2020:2–3. Available from: . Accessed July 14, 2022.
    1. Schiffman M, Castle PE, Jeronimo J, Rodriguez AC, Wacholder S. Human papillomavirus and cervical cancer. Lancet. 2007;370(9590):890–907. doi:10.1016/S0140-6736(07)61416-0
    1. Roden RBS, Stern PL. Opportunities and challenges for human papillomavirus vaccination in cancer. Nature Rev Cancer. 2019;18(4):240–254. doi:10.1038/nrc.2018.13.Opportunities
    1. Federal Democratic Republic of Ethiopia Ministry of Health. Guideline for cervical cancer prevention and control in Ethiopia; 2015.
    1. Gizaw M, Teka B, Ruddies F, et al. Reasons for not attending cervical cancer screening and associated factors in Rural Ethiopia. Cancer Prev Res. 2020;13(7):593–599. doi:10.1158/1940-6207.CAPR-19-0485
    1. Gizaw M, Teka B, Ruddies F, et al. Uptake of cervical cancer screening in Ethiopia by self-sampling HPV DNA compared to visual inspection with acetic acid: a cluster randomized trial. Cancer Prev Res. 2019;12(9):609–616. doi:10.1158/1940-6207.CAPR-19-0156
    1. Chauhan AS, Prinja S, Srinivasan R, et al. Cost effectiveness of strategies for cervical cancer prevention in India. PLoS One. 2020;15(9):e0238291. doi:10.1371/journal.pone.0238291
    1. Walboomers JM, Jacobs MV, Manos MM, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol. 1999;189(1):12–19. doi:10.1002/(SICI)1096-9896(199909)189:1<12::AID-PATH431>;2-F
    1. Dijkstra MG, van Zummeren M, Rozendaal L, et al. Safety of extending screening intervals beyond five years in cervical screening programmes with testing for high risk human papillomavirus: 14 year follow-up of population based randomised cohort in the Netherlands. BMJ. 2016;355:i4924. doi:10.1136/bmj.i4924
    1. Arbyn M, de Sanjose S, Saraiya M, et al. EUROGIN 2011 roadmap on prevention and treatment of HPV-related disease. Int J Cancer. 2012;131(9):1969–1982. doi:10.1002/ijc.27650
    1. Cuzick J, Adcock R, Wheeler CM. HPV genotype-specific risk for cervical cancer; 2021. Available from: . Accessed July 14, 2022.
    1. Arbyn M, Simon M, Peeters E, et al. 2020 list of human papillomavirus assays suitable for primary cervical cancer screening. Clin Microbiol Infect. 2021;27(8):1083–1095. doi:10.1016/j.cmi.2021.04.031
    1. World Health Organisation. WHO Guideline for Screening and Treatment of Cervical Pre-Cancer Lesions for Cervical Cancer Prevention. 2nd ed. Geneva: World Health Organisation; 2021.
    1. Poljak M, Oštrbenk Valenčak A, Gimpelj Domjanič G, Xu L, Arbyn M. Commercially available molecular tests for human papillomaviruses: a global overview. Clin Microbiol Infect. 2020;26(9):1144–1150. doi:10.1016/j.cmi.2020.03.033
    1. Elfgren K, Elfström KM, Naucler P, Arnheim-Dahlström L, Dillner J. Management of women with human papillomavirus persistence: long-term follow-up of a randomized clinical trial. Am J Obstet Gynecol. 2017;216(3):264.e1–264.e7. doi:10.1016/j.ajog.2016.10.042
    1. Jones J, Powell NG, Tristram A, Fiander AN, Hibbitts S. Comparison of the PapilloCheck® DNA micro-array human papillomavirus detection assay with hybrid capture II and PCR-enzyme immunoassay using the GP5/6+ primer set. J Clin Virol. 2009;45(2):100–104. doi:10.1016/j.jcv.2009.02.013
    1. Arbyn M, Snijders PJF, Meijer CJLM, et al. Which high-risk HPV assays fulfil criteria for use in primary cervical cancer screening? Clin Microbiol Infect. 2015;21(9):817–826. doi:10.1016/j.cmi.2015.04.015
    1. Maver PJ, Poljak M. Primary HPV-based cervical cancer screening in Europe: implementation status, challenges, and future plans. Clin Microbiol Infect. 2020;26(5):579–583. doi:10.1016/j.cmi.2019.09.006
    1. de Sanjose S, Holme F. What is needed now for successful scale-up of screening? Papillomavirus Res. 2019;7:173–175. doi:10.1016/j.pvr.2019.04.011
    1. Poljak M, Kocjan BJ, Oštrbenk A, Seme K. Commercially available molecular tests for human papillomaviruses (HPV): 2015 update. J Clin Virol. 2016;76:S3–S13. doi:10.1016/j.jcv.2015.10.023
    1. Abreu ALP, Souza RP, Gimenes F, Consolaro MEL. A review of methods for detect human Papillomavirus infection. Virol J. 2012;9:1–9. doi:10.1186/1743-422X-9-262
    1. Teka B, Gizaw M, Ruddies F, et al. Population-based human papillomavirus infection and genotype distribution among women in rural areas of South Central Ethiopia. Int J Cancer. 2021;148(3):723–730. doi:10.1002/ijc.33278
    1. Schmitt M, Dondog B, Waterboer T, Pawlita M. Homogeneous amplification of genital human alpha papillomaviruses by PCR using novel broad-spectrum GP5 ϩ and GP6 ϩ primers. J Clin Microbiol. 2008;46(3):1050–1059. doi:10.1128/JCM.02227-07
    1. Geraets DT, Cuschieri K, De Koning MNC, et al. Clinical evaluation of a GP5+/6+-based Luminex assay having full high-risk human papillomavirus genotyping capability and an internal control. J Clin Microbiol. 2014;52(11):3996–4002. doi:10.1128/JCM.01962-14
    1. Cornall AM, Poljak M, Garland SM, et al. EUROarray human papillomavirus (HPV) assay is highly concordant with other commercial assays for detection of high-risk HPV genotypes in women with high grade cervical abnormalities. Eur J Clin Microbiol Infect Dis. 2016;35(6):1033–1036. doi:10.1007/s10096-016-2634-8
    1. Hesselink AT, Sahli R, Berkhof J, et al. Clinical validation of AnyplexTM II HPV HR Detection according to the guidelines for HPV test requirements for cervical cancer screening. J Clin Virol. 2016;76:36–39. doi:10.1016/j.jcv.2016.01.009
    1. Landis JR, Koch GG. Landis and Koch 1977_agreement of categorical data. Biometrics. 1977;33(1):159–174. doi:10.2307/2529310
    1. Arbyn M, Hillemanns P. HPV assays validated for primary cervical cancer screening. HPV World. 2018;55:6–9.
    1. Wentzensen N, Arbyn M, Berkhof J, et al. Eurogin 2016 Roadmap: how HPV knowledge is changing screening practice. Int J Cancer. 2017;140(10):2192–2200. doi:10.1002/ijc.30579
    1. World Health Organization. Global Strategy Towards the Elimination of Cervical Cancer as a Public Health Problem. World Health Organization; 2019:1–24.
    1. Arbyn M, Depuydt C, Benoy I, et al. VALGENT: a protocol for clinical validation of human papillomavirus assays. J Clin Virol. 2016;76(Suppl 1):S14–S21. doi:10.1016/j.jcv.2015.09.014
    1. Cornall AM, Poljak M, Garland SM, et al. HPV genotype-specific concordance between EuroArray HPV, Anyplex II HPV28 and linear array HPV genotyping test in Australian cervical samples. Papillomavirus Res. 2017;4:79–84. doi:10.1016/j.pvr.2017.10.002
    1. Donà MG, Benevolo M, Pimpinelli F, et al. Comparative evaluation of different DNA extraction methods for HPV genotyping by linear array and INNO-LiPA. J Med Virol. 2011;83(6):1042–1047. doi:10.1002/jmv.22088
    1. Burd EM. Human papillomavirus and cervical cancer. Clin Microbiol Rev. 2003;16(1):1–17. doi:10.1128/CMR.16.1.1-17.2003
    1. IARC WG. International Agency for Research on Cancer IARC monographs on the evaluation of carcinogenic risks to humans volume 90 human papillomaviruses; 2007. Available from: . Accessed July 14, 2022.
    1. Trevethan R. Sensitivity, specificity, and predictive values: foundations, pliabilities, and pitfalls in research and practice. Front Public Heal. 2017;5:1–7. doi:10.3389/fpubh.2017.00307
    1. Saah AJ, Hoover DR. “Sensitivity” and “specificity” reconsidered: the meaning of these terms in analytical and diagnostic settings. Ann Intern Med. 1997;126(1):91–94. doi:10.7326/0003-4819-126-1-199701010-00026
    1. Kinney W, Stoler MH, Castle PE. Patient safety and the next generation of HPV DNA tests. Am J Clin Pathol. 2010;134(2):193–199. doi:10.1309/AJCPRI8XPQUEAA3K

Source: PubMed

Sponsorzy i współpracownicy

Warunki medyczne

Interwencje lekowe

3
Subskrybuj