Cancer Causes & Control

, Volume 21, Issue 5, pp 737–743 | Cite as

Human papillomavirus is not associated with colorectal cancer in a large international study

  • Michele C. Gornick
  • Xavier Castellsague
  • Gloria Sanchez
  • Thomas J. Giordano
  • Michelle Vinco
  • Joel K. Greenson
  • Gabriel Capella
  • Leon Raskin
  • Gad Rennert
  • Stephen B. Gruber
  • Victor Moreno
Original paper


Objective of the study

Recent publications have reported an association between colon cancer and human papillomaviruses (HPV), suggesting that HPV infection of the colonic mucosa may contribute to the development of colorectal cancer.


The GP5+/GP6+ PCR reverse line blot method was used for detection of 37 types of human papillomavirus (HPV) in DNA from paraffin-embedded or frozen tissues from patients with colorectal cancer (n = 279) and normal adjacent tissue (n = 30) in three different study populations, including samples from the United States (n = 73), Israel (n = 106) and Spain (n = 100). Additionally, SPF10 PCR was run on all samples (n = 279) and the Innogenetics INNO-LiPA assay was performed on a subset of samples (n = 15).


All samples were negative for all types of HPV using both the GP5+/GP6+ PCR reverse line blot method and the SPF10 INNO-LiPA method.


We conclude that HPV types associated with malignant transformation do not meaningfully contribute to adenocarcinoma of the colon.


Human papillomavirus Colorectal cancer International study 



This study was supported in part by NCI R01 CA81488, and the University of Michigan Comprehensive Cancer Center core grant (5P30 CA46592).


  1. 1.
    Bosch FX, de Sanjose S (2002) Human papillomavirus in cervical cancer. Curr Oncol Rep 4(2):175–183CrossRefPubMedGoogle Scholar
  2. 2.
    Schiffman MH, Bauer HM, Hoover RN, Glass AG, Cadell DM, Rush BB et al (1993) Epidemiologic evidence showing that human papillomavirus infection causes most cervical intraepithelial neoplasia. J Natl Cancer Inst 85(12):958–964CrossRefPubMedGoogle Scholar
  3. 3.
    zur Hausen H (1996) Papillomavirus infections—a major cause of human cancers. Biochim Biophys Acta 1288(2):F55–F78PubMedGoogle Scholar
  4. 4.
    Munoz N, Bosch FX, de Sanjose S, Herrero R, Castellsague X, Shah KV et al (2003) Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med 348(6):518–527CrossRefPubMedGoogle Scholar
  5. 5.
    Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV et al (1999) Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 189(1):12–19CrossRefPubMedGoogle Scholar
  6. 6.
    Schlecht NF, Kulaga S, Robitaille J, Ferreira S, Santos M, Miyamura RA et al (2001) Persistent human papillomavirus infection as a predictor of cervical intraepithelial neoplasia. JAMA 286(24):3106–3114CrossRefPubMedGoogle Scholar
  7. 7.
    Schiffman M, Castle PE, Jeronimo J, Rodriguez AC, Wacholder S (2007) Human papillomavirus and cervical cancer. Lancet 370(9590):890–907CrossRefPubMedGoogle Scholar
  8. 8.
    Madeleine MM, Daling JR, Carter JJ, Wipf GC, Schwartz SM, McKnight B et al (1997) Cofactors with human papillomavirus in a population-based study of vulvar cancer. J Natl Cancer Inst 89(20):1516–1523CrossRefPubMedGoogle Scholar
  9. 9.
    Goffin F, Mayrand MH, Gauthier P, Alobaid A, Lussier C, Provencher D et al (2006) High-risk human papillomavirus infection of the genital tract of women with a previous history or current high-grade vulvar intraepithelial neoplasia. J Med Virol 78(6):814–819CrossRefPubMedGoogle Scholar
  10. 10.
    Madsen BS, Jensen HL, van den Brule AJ, Wohlfahrt J, Frisch M (2008) Risk factors for invasive squamous cell carcinoma of the vulva and vagina—population-based case-control study in Denmark. Int J Cancer 122(12):2827–2834CrossRefPubMedGoogle Scholar
  11. 11.
    Daling JR, Madeleine MM, Schwartz SM, Shera KA, Carter JJ, McKnight B et al (2002) A population-based study of squamous cell vaginal cancer: HPV and cofactors. Gynecol Oncol 84(2):263–270CrossRefPubMedGoogle Scholar
  12. 12.
    Daling JR, Sherman KJ (1992) Relationship between human papillomavirus infection and tumours of anogenital sites other than the cervix. IARC Sci Publ 119:223–241PubMedGoogle Scholar
  13. 13.
    Frisch M, Glimelius B, van den Brule AJ, Wohlfahrt J, Meijer CJ, Walboomers JM et al (1997) Sexually transmitted infection as a cause of anal cancer. N Engl J Med 337(19):1350–1358CrossRefPubMedGoogle Scholar
  14. 14.
    Daling JR, Madeleine MM, Johnson LG, Schwartz SM, Shera KA, Wurscher MA et al (2004) Human papillomavirus, smoking, and sexual practices in the etiology of anal cancer. Cancer 101(2):270–280CrossRefPubMedGoogle Scholar
  15. 15.
    Bjorge T, Engeland A, Luostarinen T, Mork J, Gislefoss RE, Jellum E et al (2002) Human papillomavirus infection as a risk factor for anal and perianal skin cancer in a prospective study. Br J Cancer 87(1):61–64CrossRefPubMedGoogle Scholar
  16. 16.
    Tornesello ML, Duraturo ML, Losito S, Botti G, Pilotti S, Stefanon B et al (2008) Human papillomavirus genotypes and HPV16 variants in penile carcinoma. Int J Cancer 122(1):132–137CrossRefPubMedGoogle Scholar
  17. 17.
    Heideman DA, Waterboer T, Pawlita M, Delis-van Diemen P, Nindl I, Leijte JA et al (2007) Human papillomavirus-16 is the predominant type etiologically involved in penile squamous cell carcinoma. J Clin Oncol 25(29):4550–4556CrossRefPubMedGoogle Scholar
  18. 18.
    Daling JR, Madeleine MM, Johnson LG, Schwartz SM, Shera KA, Wurscher MA et al (2005) Penile cancer: importance of circumcision, human papillomavirus and smoking in in situ and invasive disease. Int J Cancer 116(4):606–616CrossRefPubMedGoogle Scholar
  19. 19.
    Rubin MA, Kleter B, Zhou M, Ayala G, Cubilla AL, Quint WG et al (2001) Detection and typing of human papillomavirus DNA in penile carcinoma: evidence for multiple independent pathways of penile carcinogenesis. Am J Pathol 159(4):1211–1218PubMedGoogle Scholar
  20. 20.
    Iwasawa A, Kumamoto Y, Fujinaga K (1993) Detection of human papillomavirus deoxyribonucleic acid in penile carcinoma by polymerase chain reaction and in situ hybridization. J Urol 149(1):59–63PubMedGoogle Scholar
  21. 21.
    Ritchie JM, Smith EM, Summersgill KF, Hoffman HT, Wang D, Klussmann JP et al (2003) Human papillomavirus infection as a prognostic factor in carcinomas of the oral cavity and oropharynx. Int J Cancer 104(3):336–344CrossRefPubMedGoogle Scholar
  22. 22.
    Gillison ML, Koch WM, Capone RB, Spafford M, Westra WH, Wu L et al (2000) Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. J Natl Cancer Inst 92(9):709–720CrossRefPubMedGoogle Scholar
  23. 23.
    Ringstrom E, Peters E, Hasegawa M, Posner M, Liu M, Kelsey KT (2002) Human papillomavirus type 16 and squamous cell carcinoma of the head and neck. Clin Cancer Res 8(10):3187–3192PubMedGoogle Scholar
  24. 24.
    Torrente MC, Ampuero S, Abud M, Ojeda JM (2005) Molecular detection and typing of human papillomavirus in laryngeal carcinoma specimens. Acta Otolaryngol 125(8):888–893PubMedGoogle Scholar
  25. 25.
    Almadori G, Cadoni G, Cattani P, Posteraro P, Scarano E, Ottaviani F et al (1996) Detection of human papillomavirus DNA in laryngeal squamous cell carcinoma by polymerase chain reaction. Eur J Cancer 32A(5):783–788CrossRefPubMedGoogle Scholar
  26. 26.
    Manjarrez ME, Ocadiz R, Valle L, Pacheco C, Marroquin A, De la Torre C et al (2006) Detection of human papillomavirus and relevant tumor suppressors and oncoproteins in laryngeal tumors. Clin Cancer Res 12(23):6946–6951CrossRefPubMedGoogle Scholar
  27. 27.
    Brandwein MS, Nuovo GJ, Biller H (1993) Analysis of prevalence of human papillomavirus in laryngeal carcinomas. Study of 40 cases using polymerase chain reaction and consensus primers. Ann Otol Rhinol Laryngol 102(4 Pt 1):309–313PubMedGoogle Scholar
  28. 28.
    Perez LO, Abba MC, Laguens RM, Golijow CD (2005) Analysis of adenocarcinoma of the colon and rectum: detection of human papillomavirus (HPV) DNA by polymerase chain reaction. Colorectal Dis 7(5):492–495CrossRefPubMedGoogle Scholar
  29. 29.
    Bodaghi S, Yamanegi K, Xiao SY, Da Costa M, Palefsky JM, Zheng ZM (2005) Colorectal papillomavirus infection in patients with colorectal cancer. Clin Cancer Res 11(8):2862–2867CrossRefPubMedGoogle Scholar
  30. 30.
    Buyru N, Tezol A, Dalay N (2006) Coexistence of K-ras mutations and HPV infection in colon cancer. BMC Cancer 6:115CrossRefPubMedGoogle Scholar
  31. 31.
    Damin DC, Caetano MB, Rosito MA, Schwartsmann G, Damin AS, Frazzon AP et al (2007) Evidence for an association of human papillomavirus infection and colorectal cancer. Eur J Surg Oncol 33(5):569–574CrossRefPubMedGoogle Scholar
  32. 32.
    Shah KV, Daniel RW, Simons JW, Vogelstein B (1992) Investigation of colon cancers for human papillomavirus genomic sequences by polymerase chain reaction. J Surg Oncol 51(1):5–7CrossRefPubMedGoogle Scholar
  33. 33.
    Shroyer KR, Kim JG, Manos MM, Greer CE, Pearlman NW, Franklin WA (1992) Papillomavirus found in anorectal squamous carcinoma, not in colon adenocarcinoma. Arch Surg 127(6):741–744PubMedGoogle Scholar
  34. 34.
    de Roda Husman AM, Walboomers JM, van den Brule AJ, Meijer CJ, Snijders PJ (1995) The use of general primers GP5 and GP6 elongated at their 3′ ends with adjacent highly conserved sequences improves human papillomavirus detection by PCR. J Gen Virol 76(Pt 4):1057–1062CrossRefPubMedGoogle Scholar
  35. 35.
    Kleter B, van Doorn LJ, ter Schegget J, Schrauwen L, van Krimpen K, Burger M et al (1998) Novel short-fragment PCR assay for highly sensitive broad-spectrum detection of anogenital human papillomaviruses. Am J Pathol 153(6):1731–1739PubMedGoogle Scholar
  36. 36.
    van den Brule AJ, Pol R, Fransen-Daalmeijer N, Schouls LM, Meijer CJ, Snijders PJ (2002) GP5+/6+ PCR followed by reverse line blot analysis enables rapid and high-throughput identification of human papillomavirus genotypes. J Clin Microbiol 40(3):779–787CrossRefPubMedGoogle Scholar
  37. 37.
    Kleter B, van Doorn LJ, Schrauwen L, Molijn A, Sastrowijoto S, ter Schegget J et al (1999) Development and clinical evaluation of a highly sensitive PCR-reverse hybridization line probe assay for detection and identification of anogenital human papillomavirus. J Clin Microbiol 37(8):2508–2517PubMedGoogle Scholar
  38. 38.
    Poynter JN, Gruber SB, Higgins PD, Almog R, Bonner JD, Rennert HS et al (2005) Statins and the risk of colorectal cancer. N Engl J Med 352(21):2184–2192CrossRefPubMedGoogle Scholar
  39. 39.
    Moreno V, Gemignani F, Landi S, Gioia-Patricola L, Chabrier A, Blanco I et al (2006) Polymorphisms in genes of nucleotide and base excision repair: risk and prognosis of colorectal cancer. Clin Cancer Res 12(7 Pt 1):2101–2108CrossRefPubMedGoogle Scholar
  40. 40.
    Giordano TJ, Shedden KA, Schwartz DR, Kuick R, Taylor JM, Lee N et al (2001) Organ-specific molecular classification of primary lung, colon, and ovarian adenocarcinomas using gene expression profiles. Am J Pathol 159(4):1231–1238PubMedGoogle Scholar
  41. 41.
    Jacobs MV, Snijders PJ, van den Brule AJ, Helmerhorst TJ, Meijer CJ, Walboomers JM (1997) A general primer GP5+/GP6(+)-mediated PCR-enzyme immunoassay method for rapid detection of 14 high-risk and 6 low-risk human papillomavirus genotypes in cervical scrapings. J Clin Microbiol 35(3):791–795PubMedGoogle Scholar
  42. 42.
    DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7(3):177–188CrossRefPubMedGoogle Scholar
  43. 43.
    Ades AE, Lu G, Higgins JP (2005) The interpretation of random-effects meta-analysis in decision models. Med Decis Making 25(6):646–654CrossRefPubMedGoogle Scholar
  44. 44.
    Klug SJ, Molijn A, Schopp B, Holz B, Iftner A, Quint W et al (2008) Comparison of the performance of different HPV genotyping methods for detecting genital HPV types. J Med Virol 80(7):1264–1274CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Michele C. Gornick
    • 1
  • Xavier Castellsague
    • 2
  • Gloria Sanchez
    • 3
  • Thomas J. Giordano
    • 4
  • Michelle Vinco
    • 4
  • Joel K. Greenson
    • 4
  • Gabriel Capella
    • 2
  • Leon Raskin
    • 5
  • Gad Rennert
    • 6
  • Stephen B. Gruber
    • 1
    • 5
    • 7
  • Victor Moreno
    • 2
    • 8
  1. 1.Department of Human Genetics, School of MedicineUniversity of MichiganAnn ArborUSA
  2. 2.IDIBELL-Institut Català d’Oncologia (ICO), CIBER-ESP, L’Hospitalet de LlobregatBarcelonaSpain
  3. 3.University of AntioquiaMedellinColumbia
  4. 4.Department of Pathology, School of MedicineUniversity of MichiganAnn ArborUSA
  5. 5.Department of Internal Medicine, School of MedicineUniversity of MichiganAnn ArborUSA
  6. 6.Department of Community Medicine and Epidemiology, Carmel Medical Center, and B. Rappaport Faculty of MedicineTechnion-Israel Institute of Technology and Clalit Health Service (CHS) National Israeli Cancer Control CenterHaifaIsrael
  7. 7.Department of Epidemiology, School of Public HealthUniversity of MichiganAnn ArborUSA
  8. 8.Department of Clinical SciencesUniversity of BarcelonaBarcelonaSpain

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