Skip to main content

Advertisement

Log in

Detection and genotyping of HPV in urine samples from Chilean women attending primary health care centers

  • Original Investigation
  • Published:
Medical Microbiology and Immunology Aims and scope Submit manuscript

Abstract

Cervical cancer is the second most common malignant neoplasm in women worldwide representing approximately 10% of all types of cancers. Triage of women through cervical cytology has been an important strategy for the surveillance and control of new cases of cervical cancer. However, in many regions around the world cervical cytology has a low coverage compared to developed countries. The molecular detection of HPV is the most effective method to increase the screening sensitivity of women at risk of developing cervical cancer. There are very few studies about the efficacy of urine testing for detection of HPV in women followed up in primary health care centers. Consequently, the efficacy of using urine HPV screening in these populations has not been addressed yet. Here, we compared the detection of HPV in simultaneous urine and cervical samples of women followed up in primary health care centers. Urine and cervical samples were analyzed in 543 women attending at primary health care centers. HPV was detected by real time PCR, and HPV typing performed by PCR–RLB. A general HPV concordance of 86.2% (κ = 0.72) was determined between urine and cervical samples. The concordance for HPV-16 and 18 was almost perfect (κ = 0.82) and strong (κ = 0.77), respectively. The sensitivity and specificity for all HPV genotypes in urine using cervical samples as reference were 82.1 and 93.7%, respectively. The results showed that urine is a good alternative as clinical sample for HPV screening in women attending primary health care centers. Therefore, urine should be used as an alternative sample for increasing triage coverage either in refractory women participating in Pap surveillance programs or when cervical samples are not available.

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. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A (2015) Global cancer statistics, 2012. CA Cancer J Clin 65(2):87–108. https://doi.org/10.3322/caac.21262

    Article  PubMed  Google Scholar 

  2. Bruni L, Barrionuevo-Rosas L, Albero G, Aldea M, Serrano B, Valencia S, Brotons M, Mena M, Cosano R, Muñoz J, Bosch FX, de Sanjosé S, Castellsagué X, ICO Information Centre on HPV and Cancer (HPV Information Centre) (2016) Human Papillomavirus and Related Diseases in the World. Summary Report 2015–12-23. http://www.hpvcentre.net/summaryreport.php. Accessed 04 July 2017

  3. Chile Ministry of Health, Departamento de Estadísticas e Información de Salud (2016) Mortalidad. http://www.deis.cl/estadisticas-mortalidad/?p=51. Accessed 11 July 2017

  4. Chile Ministry of Health (2005) Encuesta Nacional De Salud Chile 2003. Enfermedades Transmisibles: Prevalencia De Virus De Hepatitis, Hantavirus y Virus Del Papiloma Humano (Informe corregido). http://epi.minsal.cl/wp-content/uploads/2016/03/InformeFinalENS2003.vet_.pdf. Accessed 28 July 2017

  5. Villa L (2006) Biology of genital human papillomaviruses. Int J Gynecol Obstet 94 (Suppl 1):S3-S7. http://screening.iarc.fr/doc/HPV%20supplement%20-%20chapter%2001.pdf

  6. Doorbar J, Quint W, Banks L, Bravo IG, Stoler M, Broker TR, Stanley MA (2012) The biology and life-cycle of human papillomaviruses. Vaccine 30(Suppl 5):F55–F70. https://doi.org/10.1016/j.vaccine.2012.06.083

    Article  CAS  PubMed  Google Scholar 

  7. Choi YJ, Park JS (2016) Clinical significance of human papillomavirus genotyping. J Gynecol Oncol 2016 Mar 27(2):e21. https://doi.org/10.3802/jgo.2016.27.e21

    Article  Google Scholar 

  8. Bosch FX, Broker TR, Forman D, Moscicki A-B, Gillison ML, Doorbar J, Stern PL, Stanley M, Arbyn M, Poljak M, Cuzick J, Castle PE, Schiller JT, Markowitz LE, Fisher WA, Canfell K, Denny LA, Franco EL, Steben M, Kane MA, Schiffman M, Meijer CJLM., Sankaranarayanan R, Castellsagué X, Kim JJ, Brotons M, Alemany L, Albero G, Diaz M, de Sanjosé S (2013) Comprehensive control of human papillomavirus infections and related diseases. ICO monograph comprehensive control of hpv infections and related diseases. Vaccine 31(Suppl 6):G1–G31. https://doi.org/10.1016/j.vaccine.2013.10.002

    Article  PubMed  Google Scholar 

  9. Aghakhani A, Mamishi S, Sabeti S, Bidari-Zerehpoosh F, Banifazl M, Bavand A, Ramezani A (2017) Gender and age-specific seroprevalence of human papillomavirus 16 and 18 in general population in Tehran, Iran. Med Microbiol Immunol 206(2):105–110. https://doi.org/10.1007/s00430-016-0487-5

    Article  CAS  PubMed  Google Scholar 

  10. Schulze MH, Völker FM, Lugert R, Cooper P, Hasenclever K, Groß U, Pfister H, Silling S (2016) High prevalence of human papillomaviruses in Ghanaian pregnant women. Med Microbiol Immunol 205(6):595–602. https://doi.org/10.1007/s00430-016-0475-9

    Article  PubMed  Google Scholar 

  11. Olson B, Gribble B, Dias J, Curryer C, Vo K, Kowal P, Byles J (2016) Cervical cancer screening programs and guidelines in low- and middle-income countries. Int J Gynaecol Obstet 134(3):239–246. https://doi.org/10.1016/j.ijgo.2016.03.011

    Article  PubMed  Google Scholar 

  12. Urrutia MT, Gajardo M (2016) Factors affecting compliance with PAP smear screening. Rev Med Chil 144(12):1553–1560. https://doi.org/10.4067/S0034-98872016001200006

    Article  PubMed  Google Scholar 

  13. Alfonzo E, Andersson Ellström A, Nemes S, Strander B (2016) Effect of fee on cervical cancer screening attendance—screenfee, a Swedish Population-Based Randomised Trial. PLoS One 11(3):e0150888. https://doi.org/10.1371/journal.pone.0150888

    Article  PubMed  PubMed Central  Google Scholar 

  14. Chile Ministry of Health, Departamento de Estadísticas e Información en Salud (2017) Cobertura (%) PAP vigente en mujeres beneficiarias de 25 a 64 años, según Región. Chile 2010–2011. http://www.deis.cl/cobertura/. Accessed 20 April 2017

  15. World Health Organization (2013) WHO guidelines for screening and treatment of precancerous lesions for cervical cancer prevention. ISBN: 978-92-4-154869-4. http://apps.who.int/iris/bitstream/10665/94830/1/9789241548694_eng.pdf. Accessed 14 August 2017

  16. Pan American Health Organization (2016) Integrating HPV testing in cervical cancer screening programs: a manual for program managers. ISBN: 978–92-75-11910-5. http://iris.paho.org/xmlui/bitstream/handle/123456789/31223/9789275319109-spa.pdf?sequence=1&isAllowed=y. Accessed 14 August 2017

  17. Balanda M, Quiero A, Vergara N, Espinoza G, Martín HS, Rojas G, Ramírez E (2016) Prevalence of human papillomavirus infection among women presenting for cervical cancer screening in Chile, 2014–2015. Med Microbiol Immunol 205(6):585–594. https://doi.org/10.1007/s00430-016-0473-y

    Article  PubMed  Google Scholar 

  18. Vergara N, Espinoza G, Balanda M, Quiero A, Hidalgo W, San Martín H, Ramírez A, Ramírez E (2017) Prevalence of Human Papillomavirus infection among Chilean women from 2012 to 2016. J Med Virol 89(9):1646–1653. https://doi.org/10.1002/jmv.24805

    Article  PubMed  Google Scholar 

  19. Obiri-Yeboah D, Adu-Sarkodie Y, Djigma F, Hayfron-Benjamin A, Abdul L, Simpore J, Mayaud P (2017) Self-collected vaginal sampling for the detection of genital human papillomavirus (HPV) using careHPV among Ghanaian women. BMC Womens Health 17(1):86. https://doi.org/10.1186/s12905-017-0448-1

    Article  PubMed  PubMed Central  Google Scholar 

  20. Anderson C, Breithaupt L, Des Marais A, Rastas C, Richman A, Barclay L, Brewer NT, Smith JS (2017) Acceptability and ease of use of mailed HPV self-collection among infrequently screened women in North Carolina. Sex Transm Infect. https://doi.org/10.1136/sextrans-2017-053235

  21. Asciutto KC, Henningsson AJ, Borgfeldt H, Darlin L, Borgfeldt C (2017) Vaginal and urine self-sampling compared to cervical sampling for HPV-testing with the Cobas 4800 HPV Test. Anticancer Res 37(8):4183–4187. https://doi.org/10.21873/anticanres.11807

    PubMed  Google Scholar 

  22. Pathak N, Dodds J, Zamora J, Khan K (2014) Accuracy of urinary human papillomavirus testing for presence of cervical HPV: systematic review and meta-analysis. BMJ 349:g5264. https://doi.org/10.1136/bmj.g5264

    Article  PubMed  PubMed Central  Google Scholar 

  23. Enerly E, Olofsson C, Nygård M (2013) Monitoring human papillomavirus prevalence in urine samples: a review. Clin Epidemiol 5:67–79. https://doi.org/10.2147/CLEP.S39799

    Article  PubMed  PubMed Central  Google Scholar 

  24. Vorsters A, Micalessi I, Bilcke J, Ieven M, Bogers J, Van Damme P (2012) Detection of human papillomavirus DNA in urine. A review of the literature. Eur J Clin Microbiol Infect Dis 31(5):627–640. https://doi.org/10.1007/s10096-011-1358-z

    Article  CAS  PubMed  Google Scholar 

  25. Stanczuk G, Baxter G, Currie H, Lawrence J, Cuschieri K, Wilson A, Arbyn M (2016) Clinical validation of hrHPV testing on vaginal and urine self-samples in primary cervical screening (cross-sectional results from the Papillomavirus Dumfries and Galloway—PaVDaG study). BMJ Open 6(4):e010660. https://doi.org/10.1136/bmjopen-2015-010660

    Article  PubMed  PubMed Central  Google Scholar 

  26. Burroni E, Bonanni P, Sani C, Lastrucci V, Carozzi F, The HPV ScreeVacc Working Group: Iossa A, Andersson KL, Brandigi L, Di Pierro C, Confortini M, Levi M, Boccalini S, Indiani L, Sala A, Tanini T, Bechini A, Azzari C (2015) Human papillomavirus prevalence in paired urine and cervical samples in women invited for cervical cancer screening. J Med Virol 87(3):508–515. https://doi.org/10.1002/jmv.24085

    Article  PubMed  Google Scholar 

  27. Nilyanimit P, Wanlapakorn N, Niruthisard S, Pohthipornthawat N, Karalak A, Laowahutanont P, Phanuphak N, Gemma N, Poovorawan Y (2013) Detection of human papillomavirus in male and female urine by electrochemical DNA chip and PCR sequencing. Asian Pac J Cancer Prev 14(9):5519–5525

    Article  PubMed  Google Scholar 

  28. 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(2):e56509. https://doi.org/10.1371/journal.pone.0056509

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Ducancelle A, Legrand MC, Pivert A, Veillon P, Le Guillou-Guillemette H, De Brux MA, Beby-Defaux A, Agius G, Hantz S, Alain S, Catala L, Descamps P, Postec E, Caly H, Charles-Pétillon F, Labrousse F, Lunel F, Payan C (2014) Interest of human papillomavirus DNA quantification and genotyping in paired cervical and urine samples to detect cervical lesions. Arch Gynecol Obstet 290(2):299–308. https://doi.org/10.1007/s00404-014-3191-y

    CAS  PubMed  Google Scholar 

  30. Hagihara M, Yamagishi Y, Izumi K, Miyazaki N, Suzuki T, Kato H, Nishiyama N, Koizumi Y, Suematsu H, Mikamo H (2016) Comparison of initial stream urine samples and cervical samples for detection of human papillomavirus. J Infect Chemother 22(8):559–562. https://doi.org/10.1016/j.jiac.2016.05.009

    Article  PubMed  Google Scholar 

  31. Cómbita AL, Gheit T, González P, Puerto D, Murillo RH, Montoya L, Vorsters A, Van Keer S, Van Damme P, Tommasino M, Hernández-Suárez G, Sánchez L, Herrero R, Wiesner C (2016) Comparison between urine and cervical samples for HPV DNA detection and typing in young women in Colombia. Cancer Prev Res 9(9):766–771. https://doi.org/10.1158/1940-6207.CAPR-16-0038

    Article  Google Scholar 

  32. Coutlée F, Gravitt P, Kornegay J, Hankins C, Richardson H, Lapointe N, Voyer H, Franco E (2002) Use of PGMY primers in L1 consensus PCR improves detection of human papillomavirus DNA in genital samples. J Clin Microbiol 40(3):902–907. https://doi.org/10.1128/JCM.40.3.902-907.2002

    Article  PubMed  PubMed Central  Google Scholar 

  33. Montanheiro PA, Penalva de Oliveira AC, Posada-Vergara MP, Milagres AC, Tauil C, Marchiori PE, Duarte AJ, Casseb J (2005) Human T-cell lymphotropic virus type I (HTLV-I) proviral DNA viral load among asymptomatic patients and patients with HTLV-I-associated myelopathy/tropical spastic paraparesis. Braz J Med Biol Res 38(11):1643–1647. https://doi.org/10.1590/S0100-879X2005001100011

    Article  CAS  PubMed  Google Scholar 

  34. World Health Organization (2010) Human papillomavirus laboratory manual, First edition. WHO/IVB/10.12. http://whqlibdoc.who.int/hq/2010/WHO_IVB_10.12_eng.pdf. Accessed 16 August 2017

  35. Olson B, Gribble B, Dias J, Curryer C, Vo K, Kowal P, Byles J (2016) Cervical cancer screening programs and guidelines in low- and middle-income countries. Int J Gynaecol Obstet 134(3):239–246. https://doi.org/10.1016/j.ijgo.2016.03.011

    Article  PubMed  Google Scholar 

  36. Senapathy JG, Umadevi P, Kannika PS (2011) The present scenario of cervical cancer control and HPV epidemiology in India: an outline. Asian Pac J Cancer Prev 12(5):1107–1115

    PubMed  Google Scholar 

  37. Gu C, Chan CW, Twinn S (2010) How sexual history and knowledge of cervical cancer and screening influence Chinese women’s screening behavior in mainland China. Cancer Nurs 33(6):445–453. https://doi.org/10.1097/NCC.0b013e3181e456dc

    Article  PubMed  Google Scholar 

  38. Marván ML, Ehrenzweig Y, Catillo-López RL (2013) Knowledge about cervical cancer prevention and psychosocial barriers to screening among Mexican women. J Psychosom Obstet Gynaecol 34(4):163–169. https://doi.org/10.3109/0167482X.2013.846904

    Article  PubMed  Google Scholar 

  39. Basu P, Sarkar S, Mukherjee S, Ghoshal M, Mittal S, Biswas S, Mandal R, Sankaranarayanan R (2006) Women’s perceptions and social barriers determine compliance to cervical screening: results from a population based study in India. Cancer Detect Prev 30(4):369–374. https://doi.org/10.1016/j.cdp.2006.07.004

    Article  PubMed  Google Scholar 

  40. Liang W, Wang JH, Chen MY, Feng S, Lee M, Schwartz MD, Pasick RJ, Mandelblatt JS (2008) Developing and validating a measure of Chinese cultural views of health and cancer. Health Educ Behav 35(3):361–375. https://doi.org/10.1177/1090198106294893

    Article  PubMed  Google Scholar 

  41. Urrutia MT, Poupin L, Concha X, Viñales D, Iglesias C, Reyes V (2008) ¿Por qué las mujeres no se toman el Papapnicolau? Barreras percibidas por un grupo de mujeres ingresadas al programa de cáncer cérvico uterino AUGE. Rev Chil Obstet Ginecol 73(2):98–103

    Google Scholar 

  42. Piyathilake CJ, Badiga S, Chambers MM, Brill IK, Matthews R, Partridge EE (2016) Accuracy of urinary human papillomavirus testing for the presence of cervical human papillomaviruses and higher grades of cervical intraepithelial neoplasia. Cancer 122(18):2836–2844. https://doi.org/10.1002/cncr.30123

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Sahasrabuddhe VV, Gravitt PE, Dunn ST, Brown D, Allen RA, Eby YJ, Smith K, Zuna RE, Zhang RR, Gold MA, Schiffman M, Walker JL, Castle PE, Wentzensen N (2014) Comparison of human papillomavirus detections in urine, vulvar, and cervical samples from women attending a colposcopy clinic. J Clin Microbiol 52(1):187–192. https://doi.org/10.1128/JCM.01623-13

    Article  PubMed  PubMed Central  Google Scholar 

  44. Bernal S, Palomares JC, Artura A, Parra M, Cabezas JL, Robles A, Martín Mazuelos E (2014) Comparison of urine and cervical samples for detecting human papillomavirus (HPV) with the Cobas 4800 HPV test. J Clin Virol 61(4):548–552. https://doi.org/10.1016/j.jcv.2014.10.001

    Article  CAS  PubMed  Google Scholar 

  45. Nicolau P, Mancebo G, Agramunt S, Solé-Sedeño JM, Bellosillo B, Muset MM, Lloveras B, Alameda F, Carreras R (2014) Urine human papillomavirus prevalence in women with high-grade cervical lesions. Eur J Obstet Gynecol Reprod Biol 183:12–15. https://doi.org/10.1016/j.ejogrb.2014.10.005

    Article  CAS  PubMed  Google Scholar 

  46. Van Keer S, Pattyn J, Tjalma WAA, Van Ostade X, Ieven M, Van Damme P, Vorsters A (2017) First-void urine: a potential biomarker source for triage of high-risk human papillomavirus infected women. Eur J Obstet Gynecol Reprod Biol 216:1–11. https://doi.org/10.1016/j.ejogrb.2017.06.036

    Article  PubMed  Google Scholar 

  47. Vorsters A, Van den Bergh J, Micalessi I, Biesmans S, Bogers J, Hens A, De Coster I, Ieven M, Van Damme P (2014) Optimization of HPV DNA detection in urine by improving collection, storage, and extraction. Eur J Clin Microbiol Infect Dis 33(11):2005–2014. https://doi.org/10.1007/s10096-014-2147-2

    Article  CAS  PubMed  Google Scholar 

  48. Senkomago V, Des Marais AC, Rahangdale L, Vibat CR, Erlander MG, Smith JS (2016) Comparison of urine specimen collection times and testing fractions for the detection of high-risk human papillomavirus and high-grade cervical precancer. J Clin Virol 74:26–31. https://doi.org/10.1016/j.jcv.2015.11.005

    Article  CAS  PubMed  Google Scholar 

  49. Tshomo U, Franceschi S, Tshokey T, Tobgay T, Baussano I, Tenet V, Snijders PJ, Gheit T, Tommasino M, Vorsters A, Clifford GM (2017) Evaluation of the performance of Human Papillomavirus testing in paired urine and clinician-collected cervical samples among women aged over 30 years in Bhutan. Virol J 14(1):74. https://doi.org/10.1186/s12985-017-0744-2

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Eugenio Ramírez.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Vergara, N., Balanda, M., Hidalgo, W. et al. Detection and genotyping of HPV in urine samples from Chilean women attending primary health care centers. Med Microbiol Immunol 207, 95–103 (2018). https://doi.org/10.1007/s00430-017-0530-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00430-017-0530-1

Keywords

Navigation