Detection of human papillomavirus DNA in urine. A review of the literature

  • A. VorstersEmail author
  • I. Micalessi
  • J. Bilcke
  • M. Ieven
  • J. Bogers
  • P. Van Damme


The detection of human papillomavirus (HPV) DNA in urine, a specimen easily obtained by a non-invasive self-sampling method, has been the subject of a considerable number of studies. This review provides an overview of 41 published studies; assesses how different methods and settings may contribute to the sometimes contradictory outcomes; and discusses the potential relevance of using urine samples in vaccine trials, disease surveillance, epidemiological studies, and specific settings of cervical cancer screening. Urine sampling, storage conditions, sample preparation, DNA extraction, and DNA amplification may all have an important impact on HPV DNA detection and the form of viral DNA that is detected. Possible trends in HPV DNA prevalence in urine could be inferred from the presence of risk factors or the diagnosis of cervical lesions. HPV DNA detection in urine is feasible and may become a useful tool but necessitates further improvement and standardization.


Polymerase Chain Reaction Inhibitor Cervical Cancer Screening Program Viral Episome Polymerase Chain Reaction Setting Abnormal Cervical Cytology Result 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This work was financially supported by the Industrial Research Fund (with the participation of GlaxoSmithKline Biologicals) of the University of Antwerp (IOF/SBO 3501/3494). The funding sources had no role in the study design, collection of data, analysis, and interpretation of the data; in the writing of the report; and in the decision to submit the paper for publication.

Conflicts of interest

Pierre van Damme is the promoter, and Margareta Ieven and Johannes Bogers are the co-promoters of this research project, for which the University obtains a 10% financial contribution from GSK Biologicals. Alex Vorsters, Isabel Micalessi, and Joke Bilcke have no conflicts of interest.


  1. 1.
    Moscicki AB, Schiffman M, Kjaer S, Villa LL (2006) Chapter 5: Updating the natural history of HPV and anogenital cancer. Vaccine 24(Suppl 3):S3/42–S3/51Google Scholar
  2. 2.
    Einstein MH, Schiller JT, Viscidi RP, Strickler HD, Coursaget P, Tan T, Halsey N, Jenkins D (2009) Clinician’s guide to human papillomavirus immunology: knowns and unknowns. Lancet Infect Dis 9(6):347–356PubMedCrossRefGoogle Scholar
  3. 3.
    Wright TC, Bosch FX, Franco EL, Cuzick J, Schiller JT, Garnett GP, Meheus A (2006) Chapter 30: HPV vaccines and screening in the prevention of cervical cancer; conclusions from a 2006 workshop of international experts. Vaccine 24(Suppl 3):S3/251–S3/261Google Scholar
  4. 4.
    Kyrgiou M, Koliopoulos G, Martin-Hirsch P, Arbyn M, Prendiville W, Paraskevaidis E (2006) Obstetric outcomes after conservative treatment for intraepithelial or early invasive cervical lesions: systematic review and meta-analysis. Lancet 367(9509):489–498PubMedCrossRefGoogle Scholar
  5. 5.
    zur Hausen H (1991) Viruses in human cancers. Science 254(5035):1167–1173PubMedCrossRefGoogle Scholar
  6. 6.
    van Doorn LJ, Molijn A, Kleter B, Quint W, Colau B (2006) Highly effective detection of human papillomavirus 16 and 18 DNA by a testing algorithm combining broad-spectrum and type-specific PCR. J Clin Microbiol 44(9):3292–3298PubMedCrossRefGoogle Scholar
  7. 7.
    Jenkins D (2008) A review of cross-protection against oncogenic HPV by an HPV-16/18 AS04-adjuvanted cervical cancer vaccine: importance of virological and clinical endpoints and implications for mass vaccination in cervical cancer prevention. Gynecol Oncol 110(3 Suppl 1):S18–S25PubMedCrossRefGoogle Scholar
  8. 8.
    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(5):513–518PubMedGoogle Scholar
  9. 9.
    Khan G, Kangro HO, Coates PJ, Heath RB (1991) Inhibitory effects of urine on the polymerase chain reaction for cytomegalovirus DNA. J Clin Pathol 44(5):360–365PubMedCrossRefGoogle Scholar
  10. 10.
    Milde A, Haas-Rochholz H, Kaatsch HJ (1999) Improved DNA typing of human urine by adding EDTA. Int J Legal Med 112(3):209–210PubMedCrossRefGoogle Scholar
  11. 11.
    Carder C, Robinson AJ, Broughton C, Stephenson JM, Ridgway GL (1999) Evaluation of self-taken samples for the presence of genital Chlamydia trachomatis infection in women using the ligase chain reaction assay. Int J STD AIDS 10(12):776–779PubMedCrossRefGoogle Scholar
  12. 12.
    Howard M, Sellors J, Kaczorowski J, Lorincz A (2004) Optimal cutoff of the hybrid capture II human papillomavirus test for self-collected vaginal, vulvar, and urine specimens in a colposcopy referral population. J Low Genit Tract Dis 8(1):33–37PubMedCrossRefGoogle Scholar
  13. 13.
    Baldwin SB, Wallace DR, Papenfuss MR, Abrahamsen M, Vaught LC, Kornegay JR, Hallum JA, Redmond SA, Giuliano AR (2003) Human papillomavirus infection in men attending a sexually transmitted disease clinic. J Infect Dis 187(7):1064–1070PubMedCrossRefGoogle Scholar
  14. 14.
    Chen Z, Ye Z, Zeng W (2004) Clinical investigation on the correlation between lower urinary tract infection and cystitis glandularis. J Huazhong Univ Sci Technolog Med Sci 24(3):303–304PubMedCrossRefGoogle Scholar
  15. 15.
    Alameda F, Bellosillo B, Fusté P, Musset M, Mariñoso 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(1):5–7PubMedCrossRefGoogle Scholar
  16. 16.
    Astori G, Pipan C, Muffato G, Botta GA (1995) Detection of HPV-DNA in semen, urine and urethral samples by dot blot and PCR. New Microbiol 18(2):143–149PubMedGoogle Scholar
  17. 17.
    Brinkman JA, Jones WE, Gaffga AM, Sanders JA, Chaturvedi AK, Slavinsky J 3rd, 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(9):3155–3161PubMedCrossRefGoogle Scholar
  18. 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(4):230–240PubMedCrossRefGoogle Scholar
  19. 19.
    Costa FA, da Silva RC, Arruda LB, Duarte AJ, Casseb J (2009) Prevalence of human papillomaviruses in urine samples of male patients infected with HIV-1 in Sao Paulo, Brazil. J Med Virol 81(12):2007–2011PubMedCrossRefGoogle Scholar
  20. 20.
    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(3):189–193PubMedCrossRefGoogle Scholar
  21. 21.
    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(6):619–621PubMedCrossRefGoogle Scholar
  22. 22.
    D’Hauwers K, Depuydt C, Bogers JP, Stalpaert M, Vereecken A, Wyndaele JJ, Tjalma W (2007) Urine versus brushed samples in human papillomavirus screening: study in both genders. Asian J Androl 9(5):705–710PubMedCrossRefGoogle Scholar
  23. 23.
    Fambrini M, Penna C, Pieralli A, Bussani C, Fallani MG, Andersson KL, Scarselli G, Marchionni M (2008) PCR detection rates of high risk human papillomavirus DNA in paired self-collected urine and cervical scrapes after laser CO2 conization for high-grade cervical intraepithelial neoplasia. Gynecol Oncol 109(1):59–64PubMedCrossRefGoogle Scholar
  24. 24.
    Feng Q, Hawes SE, Stern JE, Dem A, Sow PS, Dembele B, Toure P, Sova P, Laird PW, Kiviat NB (2007) Promoter hypermethylation of tumor suppressor genes in urine from patients with cervical neoplasia. Cancer Epidemiol Biomarkers Prev 16(6):1178–1184PubMedCrossRefGoogle Scholar
  25. 25.
    Fife KH, Coplan PM, Jansen KU, DiCello AC, Brown DR, Rojas C, Su L (2003) Poor sensitivity of polymerase chain reaction assays of genital skin swabs and urine to detect HPV 6 and 11 DNA in men. Sex Transm Dis 30(3):246–248PubMedCrossRefGoogle Scholar
  26. 26.
    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(8):1975–1979PubMedGoogle Scholar
  27. 27.
    Geddy PM, Wells M, Lacey CJ (1993) Lack of detection of human papillomavirus DNA in male urine samples. Genitourin Med 69(4):276–279PubMedGoogle Scholar
  28. 28.
    Giuliano AR, Nielson CM, Flores R, Dunne EF, Abrahamsen M, Papenfuss MR, Markowitz LE, Smith D, Harris RB (2007) The optimal anatomic sites for sampling heterosexual men for human papillomavirus (HPV) detection: the HPV detection in men study. J Infect Dis 196(8):1146–1152PubMedCrossRefGoogle Scholar
  29. 29.
    Golijow CD, Pérez LO, Smith JS, Abba MC (2005) Human papillomavirus DNA detection and typing in male urine samples from a high-risk population from Argentina. J Virol Methods 124(1–2):217–220PubMedCrossRefGoogle Scholar
  30. 30.
    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(3):190–194PubMedCrossRefGoogle Scholar
  31. 31.
    Hernandez BY, Wilkens LR, Zhu X, McDuffie K, Thompson P, Shvetsov YB, Ning L, Goodman MT (2008) Circumcision and human papillomavirus infection in men: a site-specific comparison. J Infect Dis 197(6):787–794PubMedCrossRefGoogle Scholar
  32. 32.
    Hillman RJ, Botcherby M, Ryait BK, Hanna N, Taylor-Robinson D (1993) Detection of human papillomavirus DNA in the urogenital tracts of men with anogenital warts. Sex Transm Dis 20(1):21–27PubMedCrossRefGoogle Scholar
  33. 33.
    Hillman RJ, Ryait BK, Botcherby M, Taylor-Robinson D (1993) Human papillomavirus DNA in the urogenital tracts of men with gonorrhoea, penile warts or genital dermatoses. Genitourin Med 69(3):187–192PubMedGoogle Scholar
  34. 34.
    Hillman RJ, Ryait BK, Botcherby M, Walker MM, Taylor-Robinson D (1993) Human papillomavirus DNA in the urogenital tracts of men with genital dermatoses: evidence for multifocal infection. Int J STD AIDS 4(3):147–154PubMedGoogle Scholar
  35. 35.
    Iwasawa A, Hiltunen-Back E, Reunala T, Nieminen P, Paavonen J (1997) Human papillomavirus DNA in urine specimens of men with condyloma acuminatum. Sex Transm Dis 24(3):165–168PubMedCrossRefGoogle Scholar
  36. 36.
    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(8):722–728PubMedCrossRefGoogle Scholar
  37. 37.
    Jong E, Mulder JW, van Gorp EC, Wagenaar JK, Derksen J, Westerga J, Tol A, Smits PH (2008) The prevalence of human papillomavirus (HPV) infection in paired urine and cervical smear samples of HIV-infected women. J Clin Virol 41(2):111–115PubMedCrossRefGoogle Scholar
  38. 38.
    Jong E, van Gorp EC, Mulder JW, Tol A, Smits PH (2009) Effect of HIV viral load, CD4 cell count and antiretroviral therapy on human papillomavirus prevalence in urine samples of HIV-infected men. Int J STD AIDS 20(4):262–264PubMedCrossRefGoogle Scholar
  39. 39.
    Lazcano-Ponce E, Herrero R, Muñoz N, Hernandez-Avila M, Salmerón J, Leyva A, Meijer CJ, Walboomers JM (2001) High prevalence of human papillomavirus infection in Mexican males: comparative study of penile-urethral swabs and urine samples. Sex Transm Dis 28(5):277–280PubMedCrossRefGoogle Scholar
  40. 40.
    Manhart LE, Holmes KK, Koutsky LA, Wood TR, Kenney DL, Feng Q, Kiviat NB (2006) Human papillomavirus infection among sexually active young women in the United States: Implications for developing a vaccination strategy. Sex Transm Dis 33(8):502–508PubMedCrossRefGoogle Scholar
  41. 41.
    Melchers WJ, Schift R, Stolz E, Lindeman J, Quint WG (1989) Human papillomavirus detection in urine samples from male patients by the polymerase chain reaction. J Clin Microbiol 27(8):1711–1714PubMedGoogle Scholar
  42. 42.
    Nakazawa A, Inoue M, Fujita M, Tanizawa O, Hakura A (1991) Detection of human papillomavirus type 16 in sexual partners of patients having cervical cancer by polymerase chain reaction. Jpn J Cancer Res 82(11):1187–1190PubMedCrossRefGoogle Scholar
  43. 43.
    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(3):897–901PubMedCrossRefGoogle Scholar
  44. 44.
    Payan C, Tran A, Foll Y, Vallon C, Poulhazan E, Lacut K, Charles F, Herry F, Postec E, Collet M (2009) Evaluation of a new strategy for cervix cancer screening in women who do not access to pap smear screening in West Brittany, using a urine test for human papillomavirus (HPV) detection on a large scale plateform combining EasyMag extractor and real-time PCR LightCycler system (the PAPU29 PHASE 1 study). J Clin Virol 46(Suppl 1):S12CrossRefGoogle Scholar
  45. 45.
    Powell J, Strauss S, Gray J, Wojnarowska F (2003) Genital carriage of human papilloma virus (HPV) DNA in prepubertal girls with and without vulval disease. Pediatr Dermatol 20(3):191–194PubMedCrossRefGoogle Scholar
  46. 46.
    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(3):223–227PubMedCrossRefGoogle Scholar
  47. 47.
    Rintala MA, Pöllänen PP, Nikkanen VP, Grénman SE, Syrjänen SM (2002) Human papillomavirus DNA is found in the vas deferens. J Infect Dis 185(11):1664–1667PubMedCrossRefGoogle Scholar
  48. 48.
    Smits PH, Bakker R, Jong E, Mulder JW, Meenhorst PL, Kleter B, van Doorn LJ, Quint WG (2005) High prevalence of human papillomavirus infections in urine samples from human immunodeficiency virus-infected men. J Clin Microbiol 43(12):5936–5939PubMedCrossRefGoogle Scholar
  49. 49.
    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(1):110–114PubMedCrossRefGoogle Scholar
  50. 50.
    Strauss S, Jordens JZ, McBride D, Sonnex C, Edwards S, Desselberger U, Watt P, Gray JJ (1999) Detection and typing of human papillomavirus DNA in paired urine and cervical scrapes. Eur J Epidemiol 15(6):537–543PubMedCrossRefGoogle Scholar
  51. 51.
    Vossler JL, Forbes BA, Adelson MD (1995) Evaluation of the polymerase chain reaction for the detection of human papillomavirus from urine. J Med Virol 45(3):354–360PubMedCrossRefGoogle Scholar
  52. 52.
    Weaver BA, Feng Q, Holmes KK, Kiviat N, Lee SK, Meyer C, Stern M, Koutsky LA (2004) Evaluation of genital sites and sampling techniques for detection of human papillomavirus DNA in men. J Infect Dis 189(4):677–685PubMedCrossRefGoogle Scholar
  53. 53.
    Zambrano A, Kalantari M, Simoneau A, Jensen JL, Villarreal LP (2002) Detection of human polyomaviruses and papillomaviruses in prostatic tissue reveals the prostate as a habitat for multiple viral infections. Prostate 53(4):263–276PubMedCrossRefGoogle Scholar
  54. 54.
    Johnson DJ, Calderaro AC, Roberts KA (2007) Variation in nuclear DNA concentrations during urination. J Forensic Sci 52(1):110–113PubMedCrossRefGoogle Scholar
  55. 55.
    Baker T (2009) Methods and reagents for preservation of DNA in bodily fluids. United States Patent application publication, pp 1–24Google Scholar
  56. 56.
    Bierau K (2008) Improved urine sample collecting and processing. WIPO International Application published under the patent cooperation treaty, pp 1–91Google Scholar
  57. 57.
    McMillian RA (2003) Method for preservation of cells and nucleic acid targets. United States Patent application publication, pp 1–9Google Scholar
  58. 58.
    Su YH, Wang M, Brenner DE, Norton PA, Block TM (2008) Detection of mutated K-ras DNA in urine, plasma, and serum of patients with colorectal carcinoma or adenomatous polyps. Ann N Y Acad Sci 1137:197–206PubMedCrossRefGoogle Scholar
  59. 59.
    Su YH, Wang M, Brenner DE, Ng A, Melkonyan H, Umansky S, Syngal S, Block TM (2004) Human urine contains small, 150 to 250 nucleotide-sized, soluble DNA derived from the circulation and may be useful in the detection of colorectal cancer. J Mol Diagn 6(2):101–107PubMedCrossRefGoogle Scholar
  60. 60.
    Shekhtman EM, Anne K, Melkonyan HS, Robbins DJ, Warsof SL, Umansky SR (2009) Optimization of transrenal DNA analysis: detection of fetal DNA in maternal urine. Clin Chem 55(4):723–729PubMedCrossRefGoogle Scholar
  61. 61.
    Birch NC, Stickle DF, Young A, Medina P, Hinrichs SH (2003) Evaluation of urine specimen integrity in a public health STD screening program. Am J Clin Pathol 119(4):516–521PubMedCrossRefGoogle Scholar
  62. 62.
    Middleton K, Peh W, Southern S, Griffin H, Sotlar K, Nakahara T, El-Sherif A, Morris L, Seth R, Hibma M, Jenkins D, Lambert P, Coleman N, Doorbar J (2003) Organization of human papillomavirus productive cycle during neoplastic progression provides a basis for selection of diagnostic markers. J Virol 77(19):10186–10201PubMedCrossRefGoogle Scholar
  63. 63.
    Bryzgunova OE, Skvortsova TE, Kolesnikova EV, Starikov AV, Rykova EY, Vlassov VV, Laktionov PP (2006) Isolation and comparative study of cell-free nucleic acids from human urine. Ann N Y Acad Sci 1075:334–340PubMedCrossRefGoogle Scholar
  64. 64.
    D’Hauwers KW, Tjalma WA (2009) Screening for human papillomavirus: is urine useful? Indian J Cancer 46(3):190–193PubMedCrossRefGoogle Scholar
  65. 65.
    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(7):583–589PubMedCrossRefGoogle Scholar
  66. 66.
    Song ES, Lee HJ, Hwang TS (2007) Clinical efficacy of human papillomavirus DNA detection in urine from patients with various cervical lesions. J Korean Med Sci 22(1):99–104PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • A. Vorsters
    • 1
    Email author
  • I. Micalessi
    • 2
    • 1
  • J. Bilcke
    • 3
  • M. Ieven
    • 4
  • J. Bogers
    • 2
  • P. Van Damme
    • 1
  1. 1.Centre for the Evaluation of Vaccination, Vaccine and Infectious Disease InstituteUniversity of Antwerp, Faculty of Medicine, Campus Drie EikenAntwerpenBelgium
  2. 2.Applied Molecular Biology Research, Laboratory of Cell Biology and HistologyUniversity of AntwerpAntwerpenBelgium
  3. 3.Centre for Health Economic Evaluations and Modelling Infectious Diseases, Centre for the Evaluation of Vaccination, Vaccine and Infectious Disease InstituteUniversity of AntwerpAntwerpenBelgium
  4. 4.Laboratory for Microbiology, Vaccine and Infectious Disease InstituteUniversity Hospital Antwerp, University of AntwerpEdegemBelgium

Personalised recommendations