Skip to main content

Advertisement

Log in

Interest of Human Papillomavirus DNA quantification and genotyping in paired cervical and urine samples to detect cervical lesions

  • General Gynecology
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Background

Cervical cancer is caused by persistent infection with high-risk human papillomavirus (HR-HPV). Conventional human papillomavirus (HPV) testing requires cervical sampling. However, vaginal and urine self-sampling methods are more acceptable for patients and result in increased participation when they are available in screening programs. In this context, we have developed a non-invasive screening method via the detection of HPV DNA in urine samples.

Purpose

To compare HPV viral loads and genotypes in paired cervical and urine samples, and to assess correlation between virological and cytological results in women seeking gynecological consultation.

Methods

Paired urine and cervical specimens were collected and analyzed from 230 of 245 women participating in the previously described prospective PapU study. HPV DNA detection and quantification were performed using a real-time PCR method with short fragment PCR primers. Genotyping was carried out using the INNO-LiPA HPV genotyping assay.

Results

The prevalence of HPV in the 230 paired urine and cervical smear samples was 42 and 49 %, respectively. Overall agreement for HPV positivity and negativity between the paired samples was 90 % (κ = 0.80). High HPV viral load in both cervical and urine samples was associated with cytological abnormalities. HPV-positive women were mostly infected with HR-HPV types. The agreement between high- and low-risk HPV (LR-HPV) detection in both samples was 97 % (κ = 0.95 for HR-HPV and κ = 0.97 for LR-HPV).

Conclusions

High concordance rates for HPV-DNA quantification and high/low-risk HPV genotyping in paired urine/cervical samples suggest that urinary HPV DNA testing could be useful for cervical lesion screening.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Munoz N, Bosch FX, de Sanjose S, Herrero R, Castellsague X, Shah KV, Snijders PJ, Meijer CJ (2003) Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med 348:518–527

    Article  PubMed  Google Scholar 

  2. Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, Snijders PJ, Peto J, Meijer CJ, Munoz N (1999) Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 189:12–19

    Article  CAS  PubMed  Google Scholar 

  3. Schmitz M, Scheungraber C, Herrmann J, Teller K, Gajda M, Runnebaum IB, Durst M (2009) Quantitative multiplex PCR assay for the detection of the seven clinically most relevant high-risk HPV types. J Clin Virol 44:302–307

    Article  CAS  PubMed  Google Scholar 

  4. Cuzick J, Clavel C, Petry KU, Meijer CJ, Hoyer H, Ratnam S, Szarewski A, Birembaut P, Kulasingam S, Sasieni P, Iftner T (2006) Overview of the European and North American studies on HPV testing in primary cervical cancer screening. Int J Cancer 119:1095–1101

    Article  CAS  PubMed  Google Scholar 

  5. Kyrgiou M, Koliopoulos G, Martin-Hirsch P, Kehoe S, Flannelly G, Mitrou S, Arbyn M, Prendiville W, Paraskevaidis E (2007) Management of minor cervical cytological abnormalities: a systematic review and a meta-analysis of the literature. Cancer Treat Rev 33:514–520

    Article  CAS  PubMed  Google Scholar 

  6. Cuzick J, Arbyn M, Sankaranarayanan R, Tsu V, Ronco G, Mayrand MH, Dillner J, Meijer CJ (2008) Overview of human papillomavirus-based and other novel options for cervical cancer screening in developed and developing countries. Vaccine 26(Suppl 10):K29–K41

    Article  PubMed  Google Scholar 

  7. Daponte A, Tsezou A, Oikonomou P, Hadjichristodoulou C, Maniatis AN, Pournaras S, Messinis IE (2008) Use of real-time PCR to detect human papillomavirus-16 viral loads in vaginal and urine self-sampled specimens. Clin Microbiol Infect 14:619–621

    Article  CAS  PubMed  Google Scholar 

  8. Daponte A, Pournaras S, Mademtzis I, Hadjichristodoulou C, Kostopoulou E, Maniatis AN, Messinis IE (2006) Evaluation of HPV 16 PCR detection in self- compared with clinician-collected samples in women referred for colposcopy. Gynecol Oncol 103:463–466

    Article  CAS  PubMed  Google Scholar 

  9. Sellors JW, Lorincz AT, Mahony JB, Mielzynska I, Lytwyn A, Roth P, Howard M, Chong S, Daya D, Chapman W, Chernesky M (2000) Comparison of self-collected vaginal, vulvar and urine samples with physician-collected cervical samples for human papillomavirus testing to detect high-grade squamous intraepithelial lesions. CMAJ 163:513–518

    CAS  PubMed Central  PubMed  Google Scholar 

  10. Tamalet C, Le Retraite L, Leandri FX, Heid P, Sancho Garnier H, Piana L (2013) Vaginal self-sampling is an adequate means of screening HR-HPV types in women not participating in regular cervical cancer screening. Clin Microbiol Infect 19:E44–E50

    Article  CAS  PubMed  Google Scholar 

  11. Leo E, Venturoli S, Cricca M, Musiani M, Zerbini M (2009) High-throughput two-step LNA real time PCR assay for the quantitative detection and genotyping of HPV prognostic-risk groups. J Clin Virol 45:304–310

    Article  CAS  PubMed  Google Scholar 

  12. De Araujo MR, De Marco L, Santos CF, Rubira-Bullen IR, Ronco G, Pennini I, Vizzini L, Merletti F, Gillio-Tos A (2009) GP5+/6+ SYBR Green methodology for simultaneous screening and quantification of human papillomavirus. J Clin Virol 45:90–95

    Article  PubMed  Google Scholar 

  13. Winer RL, Harris TG, Xi LF, Jansen KU, Hughes JP, Feng Q, Welebob C, Ho J, Lee SK, Carter JJ, Galloway DA, Kiviat NB, Koutsky LA (2009) Quantitative human papillomavirus 16 and 18 levels in incident infections and cervical lesion development. J Med Virol 81:713–721

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Carcopino X, Henry M, Benmoura D, Fallabregues AS, Richet H, Boubli L, Tamalet C (2006) Determination of HPV type 16 and 18 viral load in cervical smears of women referred to colposcopy. J Med Virol 78:1131–1140

    Article  CAS  PubMed  Google Scholar 

  15. Sehgal A, Gupta S, Parashari A, Sodhani P, Singh V (2009) Urine HPV-DNA detection for cervical cancer screening: prospects and prejudices. J Obstet Gynaecol 29:583–589

    Article  CAS  PubMed  Google Scholar 

  16. Prusty BK, Kumar A, Arora R, Batra S, Das BC (2005) Human papillomavirus (HPV) DNA detection in self-collected urine. Int J Gynaecol Obstet 90:223–227

    Article  CAS  PubMed  Google Scholar 

  17. Cheng A, Qian Q, Kirby JE (2012) Evaluation of the Abbott RealTime CT/NG assay in comparison to the Roche Cobas Amplicor CT/NG assay. J Clin Microbiol 49:1294–1300

    Article  Google Scholar 

  18. Brinkman JA, Rahmani MZ, Jones WE, Chaturvedi AK, Hagensee ME (2004) Optimization of PCR based detection of human papillomavirus DNA from urine specimens. J Clin Virol 29:230–240

    Article  CAS  PubMed  Google Scholar 

  19. Jacobson DL, Womack SD, Peralta L, Zenilman JM, Feroli K, Maehr J, Daniel RW, Shah KV (2000) Concordance of human papillomavirus in the cervix and urine among inner city adolescents. Pediatr Infect Dis J 19:722–728

    Article  CAS  PubMed  Google Scholar 

  20. Brinkman JA, Jones WE, Gaffga AM, Sanders JA, Chaturvedi AK, Slavinsky IJ, Clayton JL, Dumestre J, Hagensee ME (2002) Detection of human papillomavirus DNA in urine specimens from human immunodeficiency virus-positive women. J Clin Microbiol 40:3155–3161

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Stanczuk GA, Kay P, Allan B, Chirara M, Tswana SA, Bergstrom S, Sibanda EN, Williamson AL (2003) Detection of human papillomavirus in urine and cervical swabs from patients with invasive cervical cancer. J Med Virol 71:110–114

    Article  PubMed  Google Scholar 

  22. Pieralli A, Bussani C, Andersson KL, Mattei A, Fambrini M (2009) Appendix to: “PCR detection rates of high risk human papillomavirus DNA in paired self-collected urine and cervical scrapes after laser CO(2) conization for high-grade cervical intraepithelial neoplasia”. Gynecol Oncol 116(3):586–587

    Google Scholar 

  23. Vorsters A, Micalessi I, Bilcke J, Ieven M, Bogers J, Van Damme P (2011) Detection of human papillomavirus DNA in urine. A review of the literature. Eur J Clin Microbiol Infect Dis 31:627–640

    Article  PubMed  Google Scholar 

  24. Payan C, Ducancelle A, Aboubaker MH, Caer J, Tapia M, Chauvin A, Peyronnet D, Le Hen E, Arab Z, Legrand MC, Tran A, Postec E, Tourmen F, Avenel M, Malbois C, De Brux MA, Descamps P, Lunel F (2007) Human papillomavirus quantification in urine and cervical samples by using the Mx4000 and LightCycler general real-time PCR systems. J Clin Microbiol 45:897–901

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Cuschieri K, Nandwani R, McGough P, Cook F, Hogg L, Robertson C, Cubie H (2011) Urine testing as a surveillance tool to monitor the impact of HPV immunization programs. J Med Virol 83:1983–1987

    Article  PubMed  Google Scholar 

  26. Rymark P, Forslund O, Hansson BG, Lindholm K (1993) Genital HPV infection not a local but a regional infection: experience from a female teenage group. Genitourin Med 69:18–22

    CAS  PubMed Central  PubMed  Google Scholar 

  27. Steben M, Duarte-Franco E (2007) Human papillomavirus infection: epidemiology and pathophysiology. Gynecol Oncol 107:S2–S5

    Article  CAS  PubMed  Google Scholar 

  28. Schmitt M, Depuydt C, Benoy I, Bogers J, Antoine J, Arbyn M, Pawlita M (2013) Multiple human papillomavirus infections with high viral loads are associated with cervical lesions but do not differentiate grades of cervical abnormalities. J Clin Microbiol 51:1458–1464

    Article  PubMed Central  PubMed  Google Scholar 

  29. Alameda F, Bellosillo B, Fuste P, Musset M, Marinoso ML, Mancebo G, Lopez-Yarto MT, Carreras R, Serrano S (2007) Human papillomavirus detection in urine samples: an alternative screening method. J Low Genit Tract Dis 11:5–7

    Article  PubMed  Google Scholar 

  30. Daponte A, Pournaras S, Mademtzis I, Hadjichristodoulou C, Kostopoulou E, Maniatis AN, Messinis IE (2006) Evaluation of high-risk human papillomavirus types PCR detection in paired urine and cervical samples of women with abnormal cytology. J Clin Virol 36:189–193

    Article  CAS  PubMed  Google Scholar 

  31. Gupta A, Arora R, Gupta S, Prusty BK, Kailash U, Batra S, Das BC (2006) Human papillomavirus DNA in urine samples of women with or without cervical cancer and their male partners compared with simultaneously collected cervical/penile smear or biopsy specimens. J Clin Virol 37:190–194

    Article  CAS  PubMed  Google Scholar 

  32. Tanzi E, Bianchi S, Fasolo MM, Frati ER, Mazza F, Martinelli M, Colzani D, Beretta R, Zappa A, Orlando G (2013) High performance of a new PCR-based urine assay for HPV-DNA detection and genotyping. J Med Virol 85:91–98

    Article  CAS  PubMed  Google Scholar 

  33. Munoz M, Camargo M, Soto-De Leon SC, Sanchez R, Parra D, Pineda AC, Sussmann O, Perez-Prados A, Patarroyo ME, Patarroyo MA (2013) Human papillomavirus detection from human immunodeficiency virus-infected Colombian women’s paired urine and cervical samples. PLoS One 8:e56509

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  34. Schmitt M, Depuydt C, Benoy I, Bogers J, Antoine J, Pawlita M, Arbyn M Viral load of high-risk human papillomaviruses as reliable clinical predictor for the presence of cervical lesions. Cancer Epidemiol Biomarkers Prev. 22: 406-414

  35. Strauss S, Jordens JZ, Desselberger U, Gray JJ (2000) Single-tube real-time nested polymerase chain reaction for detecting human papillomavirus DNA. Diagn Mol Pathol 9:151–157

    Article  CAS  PubMed  Google Scholar 

  36. Monnier-Benoit S, Dalstein V, Riethmuller D, Lalaoui N, Mougin C, Pretet JL (2006) Dynamics of HPV16 DNA load reflect the natural history of cervical HPV-associated lesions. J Clin Virol 35:270–277

    Article  CAS  PubMed  Google Scholar 

  37. Snijders PJ, Hogewoning CJ, Hesselink AT, Berkhof J, Voorhorst FJ, Bleeker MC, Meijer CJ (2006) Determination of viral load thresholds in cervical scrapings to rule out CIN 3 in HPV 16, 18, 31 and 33-positive women with normal cytology. Int J Cancer 119:1102–1107

    Article  CAS  PubMed  Google Scholar 

  38. Enerly E, Olofsson C, Nygard M (2013) Monitoring human papillomavirus prevalence in urine samples: a review. Clin Epidemiol 5:67–79

    Article  PubMed Central  PubMed  Google Scholar 

  39. Forslund O, Hansson BG, Rymark P, Bjerre B (1993) Human papillomavirus DNA in urine samples compared with that in simultaneously collected urethra and cervix samples. J Clin Microbiol 31:1975–1979

    CAS  PubMed Central  PubMed  Google Scholar 

  40. Cuschieri KS, Cubie HA, Whitley MW, Seagar AL, Arends MJ, Moore C, Gilkisson G, McGoogan E (2004) Multiple high risk HPV infections are common in cervical neoplasia and young women in a cervical screening population. J Clin Pathol 57:68–72

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  41. Levi JE, Kleter B, Quint WG, Fink MC, Canto CL, Matsubara R, Linhares I, Segurado A, Vanderborght B, Neto JE, Van Doorn LJ (2002) High prevalence of human papillomavirus (HPV) infections and high frequency of multiple HPV genotypes in human immunodeficiency virus-infected women in Brazil. J Clin Microbiol 40:3341–3345

    Article  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

We express our thanks to D. Jolivet (Angers) and C. Dolou (Brest) for their helpful assistance in management, A. Pivert, B Mosset for their technical help, and K. L. Erwin for proofreading the English manuscript. The PapU study was initiated by the Angers University hospital with grants from the French Ligue Contre le Cancer, Maine-et-Loire committee (Professor Larra).

Conflict of interest

All authors declared having no conflicts of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to A. Ducancelle.

Additional information

F. Lunel and C. Payan contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ducancelle, A., Legrand, M.C., Pivert, A. et al. Interest of Human Papillomavirus DNA quantification and genotyping in paired cervical and urine samples to detect cervical lesions. Arch Gynecol Obstet 290, 299–308 (2014). https://doi.org/10.1007/s00404-014-3191-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00404-014-3191-y

Keywords

Navigation