Medical Microbiology and Immunology

, Volume 207, Issue 2, pp 95–103 | Cite as

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

  • Nicolás Vergara
  • Monserrat Balanda
  • Wilma Hidalgo
  • Héctor San Martín
  • Alexis Aceituno
  • Francisco Roldán
  • Tania Villalón
  • Melissa Hott
  • Gloria Espinoza
  • Andrea Quiero
  • María T. Valenzuela
  • Eugenio Ramírez
Original Investigation
  • 168 Downloads

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.

Keywords

Human papillomavirus Cervical samples Urine samples Chilean women 

References

  1. 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 CrossRefPubMedGoogle Scholar
  2. 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. 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. 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. 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. 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 CrossRefPubMedGoogle Scholar
  7. 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 CrossRefGoogle Scholar
  8. 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 CrossRefPubMedGoogle Scholar
  9. 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 CrossRefPubMedGoogle Scholar
  10. 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 CrossRefPubMedGoogle Scholar
  11. 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 CrossRefPubMedGoogle Scholar
  12. 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 CrossRefPubMedGoogle Scholar
  13. 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 CrossRefPubMedPubMedCentralGoogle Scholar
  14. 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. 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. 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. 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 CrossRefPubMedGoogle Scholar
  18. 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 CrossRefPubMedGoogle Scholar
  19. 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 CrossRefPubMedPubMedCentralGoogle Scholar
  20. 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. 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 PubMedGoogle Scholar
  22. 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 CrossRefPubMedPubMedCentralGoogle Scholar
  23. 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 CrossRefPubMedPubMedCentralGoogle Scholar
  24. 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 CrossRefPubMedGoogle Scholar
  25. 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 CrossRefPubMedPubMedCentralGoogle Scholar
  26. 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 CrossRefPubMedGoogle Scholar
  27. 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):5519–5525CrossRefPubMedGoogle Scholar
  28. 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 CrossRefPubMedPubMedCentralGoogle Scholar
  29. 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 PubMedGoogle Scholar
  30. 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 CrossRefPubMedGoogle Scholar
  31. 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 CrossRefGoogle Scholar
  32. 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 CrossRefPubMedPubMedCentralGoogle Scholar
  33. 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 CrossRefPubMedGoogle Scholar
  34. 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. 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 CrossRefPubMedGoogle Scholar
  36. 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):1107–1115PubMedGoogle Scholar
  37. 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 CrossRefPubMedGoogle Scholar
  38. 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 CrossRefPubMedGoogle Scholar
  39. 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 CrossRefPubMedGoogle Scholar
  40. 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 CrossRefPubMedGoogle Scholar
  41. 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):98–103Google Scholar
  42. 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 CrossRefPubMedPubMedCentralGoogle Scholar
  43. 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 CrossRefPubMedPubMedCentralGoogle Scholar
  44. 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 CrossRefPubMedGoogle Scholar
  45. 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 CrossRefPubMedGoogle Scholar
  46. 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 CrossRefPubMedGoogle Scholar
  47. 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 CrossRefPubMedGoogle Scholar
  48. 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 CrossRefPubMedGoogle Scholar
  49. 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 CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2017

Authors and Affiliations

  • Nicolás Vergara
    • 1
    • 2
  • Monserrat Balanda
    • 1
  • Wilma Hidalgo
    • 3
  • Héctor San Martín
    • 1
  • Alexis Aceituno
    • 4
    • 5
  • Francisco Roldán
    • 1
    • 3
  • Tania Villalón
    • 1
  • Melissa Hott
    • 1
  • Gloria Espinoza
    • 2
  • Andrea Quiero
    • 2
  • María T. Valenzuela
    • 6
  • Eugenio Ramírez
    • 1
  1. 1.Sección Virus Oncogénicos, Subdepto. de Enfermedades ViralesInstituto de Salud Pública de ChileSantiagoChile
  2. 2.Dirección de Atención PrimariaServicio de Salud Metropolitano CentralSantiagoChile
  3. 3.Dirección de SaludMunicipalidad de HuechurabaSantiagoChile
  4. 4.Sección Biofarmacia, Agencia Nacional de MedicamentosInstituto de Salud Pública de ChileSantiagoChile
  5. 5.Facultad de FarmaciaUniversidad de ValparaísoValparaísoChile
  6. 6.Vicedecanato Investigación y Postgrado, Facultad de MedicinaUniversidad de los AndesSantiagoChile

Personalised recommendations