1887

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Volume 69, Issue 7

Editor's Choice Correlation between cervical HPV DNA detection and HPV16 seroreactivity measured with L1-only and L1+L2 viral capsid antigens Free

Abstract

Persistent human papillomavirus (HPV) type 16 infection is the main causal agent of cervical cancer. Most HPV infections clear spontaneously within 1–2 years. Although not all infected women develop detectable HPV antibodies, about 60–70 % seroconvert and retain their antibodies at low levels.

We investigated if cervical HPV16 DNA positivity was associated with HPV16 seroreactivity measured with two different antigen formulations. We assessed if associations were influenced by co-infection with other HPV types and HPV16 viral load.

We used baseline data for women participating in the Ludwig–McGill cohort, a longitudinal investigation of the natural history of HPV infection and cervical neoplasia. The study enrolled 2462 Brazilian women from 1993 to 1997 (pre-vaccination). ELISA assays were based on L1-only or L1+L2 virus-like particles (VLPs). Seroreactivity was expressed as normalized absorbance ratios. HPV genotyping and viral load were evaluated by PCR protocols. Pearson’s was used to measure correlations between interval-scaled variables. Serological accuracy in HPV16 DNA detection was assessed using receiver operating characteristic (ROC) curves. We analysed the association between HPV DNA positivity and HPV16 seroreactivity by linear regression.

Correlations between L1+L2 and L1-only VLPs for detection of HPV16 were poor (=0.43 and 0.44 for dilutions 1 : 10 and 1 : 50, respectively). The protocol with the best accuracy was L1+L2 VLPs at serum dilution 1 : 10 (ROC area=0.73, 95 % CI: 0.65–0.85). HPV16 DNA positivity was correlated with HPV16 seroreactivity and was not influenced by co-infection or viral load. To a lesser degree, HPV16 seroreactivity was correlated with infection by other Alpha-9 papillomavirus species.

HPV16 DNA positivity and HPV16 seroreactivity are strongly correlated. L1+L2 VLPs perform better than L1-only VLPs for detecting IgG antibodies to HPV16 in women infected with HPV16 or other Alpha-9 HPV species. This study advances our understanding of humoral immune responses against HPV16 by providing insights about the influence of VLP antigen composition to measure humoral immune response against naturally acquired HPV infection.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): ELISA , HPV16 seroreactivity , Human papillomavirus , IgG antibodies , natural infection and virus-like particles
© 2020 The Authors
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2020-06-08
2024-04-18
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References

  1. zur Hausen H. Papillomaviruses and cancer: from basic studies to clinical application. Nat Rev Cancer 2002; 2:342–350 [View Article][PubMed]
     [Google Scholar]
  2. Bernard H-U, Burk RD, Chen Z, van Doorslaer K, zur Hausen H et al. Classification of papillomaviruses (PVS) based on 189 pv types and proposal of taxonomic amendments. Virology 2010; 401:70–79 [View Article][PubMed]
     [Google Scholar]
  3. Schiller JT, Lowy DR. Virus infection and human cancer: an overview. Recent Results Cancer Res 2014; 193:1–10 [View Article][PubMed]
     [Google Scholar]
  4. Bruni L, Barrionuevo-Rosas L, Albero G, Aldea M, Serrano B et al. ICO information centre on HPV and cancer (HPV information centre); 2016
  5. Bouvard V, Baan R, Straif K, Grosse Y, Secretan B et al. A review of human carcinogens--Part B: biological agents. Lancet Oncol 2009; 10:321–322 [View Article][PubMed]
     [Google Scholar]
  6. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2015; 136:E359–E386 [View Article][PubMed]
     [Google Scholar]
  7. Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 1999; 189:12–19 [View Article][PubMed]
     [Google Scholar]
  8. Trottier H, Mahmud S, Prado JCM, Sobrinho JS, Costa MC et al. Type-Specific duration of human papillomavirus infection: implications for human papillomavirus screening and vaccination. J Infect Dis 2008; 197:1436–1447 [View Article][PubMed]
     [Google Scholar]
  9. Beachler DC, Jenkins G, Safaeian M, Kreimer AR, Wentzensen N. Natural acquired immunity against subsequent genital human papillomavirus infection: a systematic review and meta-analysis. J Infect Dis 2016; 213:1444–1454 [View Article][PubMed]
     [Google Scholar]
  10. Carter JJ, Koutsky LA, Wipf GC, Christensen ND, Lee SK et al. The natural history of human papillomavirus type 16 capsid antibodies among a cohort of university women. J Infect Dis 1996; 174:927–936 [View Article][PubMed]
     [Google Scholar]
  11. Castro FA, Dominguez A, Puschel K, Van De Wyngard V, Snijders PJF et al. Serological prevalence and persistence of high-risk human papillomavirus infection among women in Santiago, Chile. BMC Infect Dis 2014; 14:361 [View Article][PubMed]
     [Google Scholar]
  12. de Araujo-Souza PS, Ramanakumar AV, Candeias JMG, Thomann P, Trevisan A et al. Determinants of baseline seroreactivity to human papillomavirus type 16 in the Ludwig-McGill cohort study. BMC Infect Dis 2014; 14:578 [View Article][PubMed]
     [Google Scholar]
  13. Dondog B, Clifford GM, Vaccarella S, Waterboer T, Unurjargal D et al. Human papillomavirus infection in Ulaanbaatar, Mongolia: a population-based study. Cancer Epidemiol Biomarkers Prev 2008; 17:1731–1738 [View Article][PubMed]
     [Google Scholar]
  14. Faust H, Jelen MM, Poljak M, Klavs I, Učakar V et al. Serum antibodies to human papillomavirus (HPV) pseudovirions correlate with natural infection for 13 genital HPV types. J Clin Virol 2013; 56:336–341 [View Article][PubMed]
     [Google Scholar]
  15. Liu F, Deng Q, Zhang C, Pan Y, Liu Y et al. Human papillomavirus DNA positivity and seropositivity in rural Chinese men and women: a population-based cross-sectional study. Sci Rep 2016; 6:26343 [View Article][PubMed]
     [Google Scholar]
  16. Nonnenmacher B, Kruger Kjaer S, Svare EI, Scott JD, Hubbert NL et al. Seroreactivity to HPV16 virus-like particles as a marker for cervical cancer risk in high-risk populations. Int J Cancer 1996; 68:704–709 [View Article][PubMed]
     [Google Scholar]
  17. Nonnenmacher B, Pintos J, Bozzetti MC, Mielzinska-Lohnas I, Lorincz AT et al. Epidemiologic correlates of antibody response to human papillomavirus among women at low risk of cervical cancer. Int J STD AIDS 2003; 14:258–265 [View Article][PubMed]
     [Google Scholar]
  18. Triglav T, Artemchuk H, Oštrbenk A, Elfström KM, Faust H et al. Effect of naturally acquired type-specific serum antibodies against human papillomavirus type 16 infection. J Clin Virol 2017; 90:64–69 [View Article][PubMed]
     [Google Scholar]
  19. Wang SS, Schiffman M, Shields TS, Herrero R, Hildesheim A et al. Seroprevalence of human papillomavirus-16, -18, -31, and -45 in a population-based cohort of 10000 women in Costa Rica. Br J Cancer 2003; 89:1248–1254 [View Article][PubMed]
     [Google Scholar]
  20. Coseo S, Porras C, Hildesheim A, Rodriguez AC, Schiffman M et al. Seroprevalence and correlates of human papillomavirus 16/18 seropositivity among young women in Costa Rica. Sex Transm Dis 2010; 37:706–714 [View Article][PubMed]
     [Google Scholar]
  21. Bjørge T, Hakulinen T, Engeland A, Jellum E, Koskela P et al. A prospective, seroepidemiological study of the role of human papillomavirus in esophageal cancer in Norway. Cancer Res 1997; 57:3989–3992[PubMed]
     [Google Scholar]
  22. Olsen AO, Dillner J, Gjøen K, Magnus P. Seropositivity against HPV 16 capsids: a better marker of past sexual behaviour than presence of HPV DNA. Genitourin Med 1997; 73:131–135 [View Article][PubMed]
     [Google Scholar]
  23. Du P, Brendle S, Milici J, Camacho F, Zurlo J et al. Comparisons of VLP-Based ELISA, neutralization assays with native HPV, and neutralization assays with PSV in detecting HPV antibody responses in HIV-infected women. J AIDS Clin Res 2015; 6: [View Article][PubMed]
     [Google Scholar]
  24. Hernandez BY, Ton T, Shvetsov YB, Goodman MT, Zhu X. Human papillomavirus (HPV) L1 and L1-L2 virus-like particle-based multiplex assays for measurement of HPV virion antibodies. Clin Vaccine Immunol 2012; 19:1348–1352 [View Article][PubMed]
     [Google Scholar]
  25. Robbins HA, Kemp TJ, Porras C, Rodriguez AC, Schiffman M et al. Comparison of antibody responses to human papillomavirus vaccination as measured by three assays. Front Oncol 2014; 3:328 [View Article][PubMed]
     [Google Scholar]
  26. Pastrana DV, Gambhira R, Buck CB, Pang Y-YS, Thompson CD et al. Cross-Neutralization of cutaneous and mucosal papillomavirus types with anti-sera to the amino terminus of L2. Virology 2005; 337:365–372 [View Article][PubMed]
     [Google Scholar]
  27. Pinto LA, Dillner J, Beddows S, Unger ER. Immunogenicity of HPV prophylactic vaccines: serology assays and their use in HPV vaccine evaluation and development. Vaccine 2018; 36:4792–4799 [View Article][PubMed]
     [Google Scholar]
  28. Franco E, Villa L, Rohan T, Ferenczy A, Petzl-Erler M et al. Design and methods of the Ludwig-McGill longitudinal study of the natural history of human papillomavirus infection and cervical neoplasia in Brazil. Ludwig-McGill Study Group. Rev Panam Salud Publica 1999; 6:223–233 [View Article][PubMed]
     [Google Scholar]
  29. Gravitt PE, Peyton CL, Alessi TQ, Wheeler CM, Coutlée F et al. Improved amplification of genital human papillomaviruses. J Clin Microbiol 2000; 38:357–361[PubMed]
     [Google Scholar]
  30. Manos MM, Ting Y, Wright DK, Lewis AJ, Broker TR et al. Use of polymerase chain reaction amplification for the detection of genital human papillomaviruses. In Furth M, Greaves M. (editors) In Molecular Diagnostic of Human Cancer, Cancer Cells New York, NY: Cold Spring Harbor Press; 1989 pp 209–214
     [Google Scholar]
  31. Ting Y, Manos MM. Detection and typing of genital human papillomaviruses. PCR protocols: a guide to methods and applications 1990356–367
     [Google Scholar]
  32. Bernard HU, Chan SY, Manos MM, Ong CK, Villa LL et al. 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; 170:1077–1085 [View Article][PubMed]
     [Google Scholar]
  33. Kirnbauer R, Hubbert NL, Wheeler CM, Becker TM, Lowy DR et al. A virus-like particle enzyme-linked immunosorbent assay detects serum antibodies in a majority of women infected with human papillomavirus type 16. J Natl Cancer Inst 1994; 86:494–499 [View Article][PubMed]
     [Google Scholar]
  34. Trottier H, Ferreira S, Thomann P, Costa MC, Sobrinho JS et al. Human papillomavirus infection and reinfection in adult women: the role of sexual activity and natural immunity. Cancer Res 2010; 70:8569–8577 [View Article][PubMed]
     [Google Scholar]
  35. Ramanakumar AV, Thomann P, Candeias JM, Ferreira S, Villa LL et al. Use of the normalized absorbance ratio as an internal standardization approach to minimize measurement error in enzyme-linked immunosorbent assays for diagnosis of human papillomavirus infection. J Clin Microbiol 2010; 48:791–796 [View Article][PubMed]
     [Google Scholar]
  36. Caballero OL, Villa LL, Simpson AJ. Low stringency-PCR (LS-PCR) allows entirely internally standardized DNA quantitation. Nucleic Acids Res 1995; 23:192–193 [View Article][PubMed]
     [Google Scholar]
  37. van den Brule AJ, Snijders PJ, Gordijn RL, Bleker OP, Meijer CJ et al. General primer-mediated polymerase chain reaction permits the detection of sequenced and still unsequenced human papillomavirus genotypes in cervical scrapes and carcinomas. Int J Cancer 1990; 45:644–649 [View Article][PubMed]
     [Google Scholar]
  38. Yee C, Krishnan-Hewlett I, Baker CC, Schlegel R, Howley PM. Presence and expression of human papillomavirus sequences in human cervical carcinoma cell lines. Am J Pathol 1985; 119:361–366[PubMed]
     [Google Scholar]
  39. de Villiers E-M, Fauquet C, Broker TR, Bernard H-U, zur Hausen H. Classification of papillomaviruses. Virology 2004; 324:17–27 [View Article][PubMed]
     [Google Scholar]
  40. Chan SY, Ho L, Ong CK, Chow V, Drescher B et al. Molecular variants of human papillomavirus type 16 from four continents suggest ancient pandemic spread of the virus and its coevolution with humankind. J Virol 1992; 66:2057–2066 [View Article][PubMed]
     [Google Scholar]
  41. Touze A, El Mehdaoui S, Sizaret PY, Mougin C, Muñoz N et al. The L1 major capsid protein of human papillomavirus type 16 variants affects yield of virus-like particles produced in an insect cell expression system. J Clin Microbiol 1998; 36:2046–2051 [View Article][PubMed]
     [Google Scholar]
  42. Iftner T, Villa LL. Chapter 12: human papillomavirus technologies. J Natl Cancer Inst Monogr 2003; 31:80–88 [View Article][PubMed]
     [Google Scholar]
  43. Namvar A, Bolhassani A, Hashemi M. Hpv16 L2 improves HPV16 L1 gene delivery as an important approach for vaccine design against cervical cancer. Bratisl Lek Listy 2016; 117:179–184 [View Article][PubMed]
     [Google Scholar]
  44. Kondo K, Ochi H, Matsumoto T, Yoshikawa H, Kanda T. Modification of human papillomavirus-like particle vaccine by insertion of the cross-reactive L2-epitopes. J Med Virol 2008; 80:841–846 [View Article][PubMed]
     [Google Scholar]
  45. Slupetzky K, Gambhira R, Culp TD, Shafti-Keramat S, Schellenbacher C et al. A papillomavirus-like particle (VLP) vaccine displaying HPV16 L2 epitopes induces cross-neutralizing antibodies to HPV11. Vaccine 2007; 25:2001–2010 [View Article][PubMed]
     [Google Scholar]
  46. Namujju PB, Surcel H-M, Kirnbauer R, Kaasila M, Banura C et al. Risk of being seropositive for multiple human papillomavirus types among Finnish and Ugandan women. Scand J Infect Dis 2010; 42:522–526 [View Article][PubMed]
     [Google Scholar]
  47. Trottier H, Mahmud S, Costa MC, Sobrinho JP, Duarte-Franco E et al. Human papillomavirus infections with multiple types and risk of cervical neoplasia. Cancer Epidemiol Biomarkers Prev 2006; 15:1274–1280 [View Article][PubMed]
     [Google Scholar]
  48. Shaw E, Ramanakumar AV, El-Zein M, Silva FR, Galan L et al. Reproductive and genital health and risk of cervical human papillomavirus infection: results from the Ludwig-McGill cohort study. BMC Infect Dis 2016; 16:116 [View Article][PubMed]
     [Google Scholar]
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Correlation between cervical HPV DNA detection and HPV16 seroreactivity measured with L1-only and L1+L2 viral capsid antigens
J. Med. Microbiol. 69, 960 (2020); https://doi.org/10.1099/jmm.0.001213
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