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World Journal of Urology

, 27:141 | Cite as

Penile cancer: epidemiology, pathogenesis and prevention

  • M. C. G. Bleeker
  • D. A. M. Heideman
  • P. J. F. Snijders
  • S. Horenblas
  • J. Dillner
  • C. J. L. M. Meijer
Topic Paper

Abstract

Objectives

Penile cancer is a disease with a high morbidity and mortality. Its prevalence is relatively rare, but the highest in some developing countries. Insight into its precursor lesions, pathogenesis and risk factors offers options to prevent this potentially mutilating disease. This review presents an overview of the different histologically and clinically identified precursor lesions of penile cancer and discusses the molecular pathogenesis, including the role of HPV in penile cancer development.

Methods

A systematic review of the literature evaluating penile carcinogenesis, risk factors and molecular mechanisms involved.

Results

Careful monitoring of men with lichen sclerosis, genital Bowen’s disease, erythroplasia of Queyrat and bowenoid papulosis seems useful, thereby offering early recognition of penile cancer and, subsequently, conservative therapeutic options. Special attention is given to flat penile lesions, which contain high numbers of HPV. Their role in HPV transmission to sexual partners is highlighted, but their potential to transform as a precursor lesion into penile cancer has been unsatisfactorily explored.

Conclusions

Further research should not only focus on HPV mediated pathogenic pathways but also on the non-HPV related molecular and genetic factors that play a role in penile cancer development. Options for prevention of penile cancer include (neonatal) circumcision, limitation of penile HPV infections (either by prophylactic vaccination or condom use), prevention of phimosis, treatment of chronic inflammatory conditions, limiting PUVA treatment, smoking cessation and hygienic measures.

Keywords

Penile cancer Penile intraepithelial neoplasia Genital Bowen’s disease Erythroplasia of Queyrat Lichen sclerosis Flat penile lesions Human papillomavirus Molecular pathogenesis Prevention 

Notes

Acknowledgments

We acknowledge professor Dr. Th.M. Starink for providing the clinical picture of bowenoid papulosis.

Conflict of interest statement

There is no conflict of interest.

References

  1. 1.
    Barnholtz-Sloan JS, Maldonado JL, Pow-sang J, Giuliano AR (2007) Incidence trends in primary malignant penile cancer. Urol Oncol 25(5):361–367PubMedGoogle Scholar
  2. 2.
    Pukkala E, Weiderpass E (2002) Socio-economic differences in incidence rates of cancers of the male genital organs in Finland, 1971–1995. Int J Cancer 102(6):643–648PubMedCrossRefGoogle Scholar
  3. 3.
    Rubin MA, Kleter B, Zhou M, Ayala G, Cubilla AL, Quint WG, Pirog EC (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
  4. 4.
    Wabinga HR, Parkin DM, Wabwire-Mangen F, Nambooze S (2000) Trends in cancer incidence in Kyadondo County, Uganda, 1960–1997. Br J Cancer 82(9):1585–1592PubMedCrossRefGoogle Scholar
  5. 5.
    Parkin DM, Muir CS (1992) Cancer incidence in five continents. Comparability and quality of data. IARC Sci Publ (120):45–173.Google Scholar
  6. 6.
    Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ (2007) Cancer statistics, 2007. CA Cancer J Clin 57(1):43–66PubMedCrossRefGoogle Scholar
  7. 7.
    Maden C, Sherman KJ, Beckmann AM, Hislop TG, Teh CZ, Ashley RL, Daling JR (1993) History of circumcision, medical conditions, and sexual activity and risk of penile cancer (see comments). J Natl Cancer Inst 85(1):19–24PubMedCrossRefGoogle Scholar
  8. 8.
    Moses S, Bailey RC, Ronald AR (1998) male circumcision: assessment of health benefits and risks. Sex Transm Infect 74(5):368–373PubMedCrossRefGoogle Scholar
  9. 9.
    Schoen EJ, Oehrli M, Colby C, Machin G (2000) The highly protective effect of newborn circumcision against invasive penile cancer. Pediatrics 105(3):E36PubMedCrossRefGoogle Scholar
  10. 10.
    Dillner J, von Krogh G, Horenblas S, Meijer CJLM (2000) Etiology of squamous cell carcinoma of the penis. Scand J Urol Nephrol 34:189–193CrossRefGoogle Scholar
  11. 11.
    Daling JR, Madeleine MM, Johnson LG, Schwartz SM, Shera KA, Wurscher MA, Carter JJ, Porter PL, Porter PL, Galloway DA, McDougall JK, Krieger JN (2005) Penile cancer: importance of circumcision, human papillomavirus and smoking in in situ and invasive disease. Int J Cancer 116(4):606–616PubMedCrossRefGoogle Scholar
  12. 12.
    Gross G, Pfister H (2004) Role of human papillomavirus in penile cancer, penile intraepithelial squamous cell neoplasias and in genital warts. Med Microbiol Immunol (Berl) 193(1):35–44CrossRefGoogle Scholar
  13. 13.
    Reddy DG, Baruah IK (1963) Carcinogenic action of human smegma. Arch Pathol 75:414–420PubMedGoogle Scholar
  14. 14.
    Misra S, Chaturvedi A, Misra NC (2004) Penile carcinoma: a challenge for the developing world. Lancet Oncol 5(4):240–247PubMedCrossRefGoogle Scholar
  15. 15.
    McCance DJ, Kalache A, Ashdown K, Andrade L, Menezes F, Smith P, Doll R (1986) Human papillomavirus types 16 and 18 in carcinomas of the penis from Brazil. Int J Cancer 37(1):55–59PubMedCrossRefGoogle Scholar
  16. 16.
    Heideman DA, Waterboer T, Pawlita M, Delis-van Diemen P, Nindl I, Leijte JA, Bonfrer JM, Horenblas S, Meijer CJ, Snijders PJ (2007) Human papillomavirus-16. Is the predominant type etiologically involved in penile squamous cell carcinoma. J Clin Oncol 25(29):4550–4556PubMedCrossRefGoogle Scholar
  17. 17.
    Gregoire L, Cubilla AL, Reuter VE, Haas GP, Lancaster WD (1995) Preferential association of human papillomavirus with high-grade histologic variants of penile-invasive squamous cell carcinoma. J Natl Cancer Inst 87(22):1705–1709PubMedCrossRefGoogle Scholar
  18. 18.
    Parkin DM, Bray F (2006) Vaccine. Chapter 2: the burden of HPV-related cancers. Suppl 3:S11–S25.Google Scholar
  19. 19.
    Bjorge T, Dillner J, Anttila T, Engeland A, Hakulinen T, Jellum E, Lehtinen M, Luostarinen T, Paavonen J, Pukkala E, Sapp M, Schiller J, Youngman L, Thoresen S (1997) Prospective seroepidemiological study of role of human papillomavirus in non-cervical anogenital cancers. BMJ 315(7109):646–649PubMedGoogle Scholar
  20. 20.
    Carter JJ, Madeleine MM, Shera K, Schwartz SM, Cushing-Haugen KL, Wipf GC, Porter P, Daling JR, McDougall JK, Galloway DA (2001) Human papillomavirus 16 and 18 l1 serology compared across anogenital cancer sites. Cancer Res 61(5):1934–1940PubMedGoogle Scholar
  21. 21.
    van Doornum GJ, Korse CM, Buning-Kager JC, Bonfrer JM, Horenblas S, Taal BG, Dillner J (2003) Reactivity to human papillomavirus type 16 l1 virus-like particles in sera from patients with genital cancer and patients with carcinomas at five different extragenital sites. Br J Cancer 88(7):1095–1100PubMedCrossRefGoogle Scholar
  22. 22.
    Newton R, Bousarghin L, Ziegler J, Casabonne D, Beral V, Mbidde E, Carpenter L, Parkin DM, Wabinga H, Mbulaiteye S, Jaffe H, Touze A, Coursaget P (2004) Human papillomaviruses and cancer in Uganda. Eur J Cancer Prev 13(2):113–118PubMedCrossRefGoogle Scholar
  23. 23.
    Dorfman S, Cavazza M, Cardozo J (2006) Penile cancer associated with so-called low-risk human papilloma virus. Report of five cases from rural Venezuela. Trop Doct 36(4):232–233PubMedCrossRefGoogle Scholar
  24. 24.
    Senba M, Kumatori A, Fujita S, Jutavijittum P, Yousukh A, Moriuchi T, Nakamura T, Toriyama K (2006) The prevalence of human papillomavirus genotypes in penile cancers from Northern Thailand. J Med Virol 78(10):1341–1346PubMedCrossRefGoogle Scholar
  25. 25.
    Wieland U, Jurk S, Weissenborn S, Krieg T, Pfister H, Ritzkowsky A (2000) Erythroplasia of queyrat: coinfection with cutaneous carcinogenic human papillomavirus type 8 and genital papillomaviruses in a carcinoma in situ. J Invest Dermatol 115(3):396–401PubMedCrossRefGoogle Scholar
  26. 26.
    Hellberg D, Valentin J, Eklund T, Nilsson S (1987) Penile cancer: is there an epidemiological role for smoking and sexual behaviour? Br Med J (Clin Res Ed) 295(6609):1306–1308Google Scholar
  27. 27.
    Harish K, Ravi R (1995) The role of tobacco in penile carcinoma. Br J Urol 75(3):375–377PubMedCrossRefGoogle Scholar
  28. 28.
    Cubilla AL, Velazquez EF, Young RH (2004) Epithelial lesions associated with invasive penile squamous cell carcinoma: a pathologic study of 288 cases. Int J Surg Pathol 12(4):351–364PubMedCrossRefGoogle Scholar
  29. 29.
    Cubilla AL, Reuter VE, Gregoire L, Ayala G, Ocampos S, Lancaster WD, Fair W (1998) Basaloid squamous cell carcinoma: a distinctive human papilloma virus- related penile neoplasm: a report of 20 cases. Am J Surg Pathol 22(6):755–761PubMedCrossRefGoogle Scholar
  30. 30.
    Cubilla AL, Velazques EF, Reuter VE, Oliva E, Mihm MC Jr, Young RH (2000) Warty (condylomatous) squamous cell carcinoma of the penis: a report of 11 cases and proposed classification of ‘verruciform’ penile tumors. Am J Surg Pathol 24(4):505–512PubMedCrossRefGoogle Scholar
  31. 31.
    van Geel AN, den Bakker MA, Kirkels W, Horenblas S, Kroon BB, de Wilt JH, Eggermont AM, Mooi WJ, van der Aa MN (2007) Prognosis of primary mucosal penile melanoma: a series of 19 Dutch patients and 47 patients from the literature. Urology 70(1):143–147PubMedCrossRefGoogle Scholar
  32. 32.
    Fetsch JF, Davis CJ Jr, Miettinen M, Sesterhenn IA (2004) Leiomyosarcoma of the penis: a clinicopathologic study of 14 cases with review of the literature and discussion of the differential diagnosis. Am J Surg Pathol 28(1):115–125PubMedCrossRefGoogle Scholar
  33. 33.
    Cubilla AL, Velazquez EF, Young RH (2004) Pseudohyperplastic squamous cell carcinoma of the penis associated with lichen sclerosus. An extremely well-differentiated, nonverruciform neoplasm that preferentially affects the foreskin and is frequently misdiagnosed: a report of 10 cases of a distinctive clinicopathologic entity. Am J Surg Pathol 28(7):895–900PubMedCrossRefGoogle Scholar
  34. 34.
    Bezerra AL, Lopes A, Santiago GH, Ribeiro KC, Latorre MR, Villa LL (2001) Human papillomavirus as a prognostic factor in carcinoma of the penis: analysis of 82 patients treated with amputation and bilateral lymphadenectomy. Cancer 91(12):2315–23211PubMedCrossRefGoogle Scholar
  35. 35.
    Ferreux E, Lont AP, Horenblas S, Gallee MPW, Raaphorst FM, Doeberitz MV, Meijer CJLM, Snijders PJF (2003) Evidence for at least three alternative mechanisms targeting the P16(INK4A)/Cyclin D/Rb Pathway in penile carcinoma, one of which is mediated by high-risk human papillomavirus. J Pathol 201(1):109–118PubMedCrossRefGoogle Scholar
  36. 36.
    Canavan TP, Cohen D (2002) Vulvar cancer. Am Fam Physician 66(7):1269–1274PubMedGoogle Scholar
  37. 37.
    Lont AP, Kroon BK, Horenblas S, Gallee MP, Berkhof J, Meijer CJ, Snijders PJ (2006) Presence of high-risk human papillomavirus DNA in penile carcinoma predicts favorable outcome in survival. Int J Cancer 119(5):1078–1081PubMedCrossRefGoogle Scholar
  38. 38.
    Barrasso R, de Brux J, Croissant O, Orth G (1987) High prevalence of papillomavirus-associated penile intraepithelial neoplasia in sexual partners of women with cervical intraepithelial neoplasia. N Engl J Med 317(15):916–923PubMedGoogle Scholar
  39. 39.
    Porter WM, Francis N, Hawkins D, Dinneen M, Bunker CB (2002) Penile intraepithelial neoplasia: clinical spectrum and treatment of 35 cases. Br J Dermatol 147(6):1159–1165PubMedCrossRefGoogle Scholar
  40. 40.
    Hahn A, Loning T, Hoos A, Henke P (1988) Immunohistochemistry (S 100, KL 1) and human papillomavirus DNA hybridization on morbus bowen and bowenoid papulosis. Virchows Arch A Pathol Anat Histopathol 413(2):113–122PubMedCrossRefGoogle Scholar
  41. 41.
    Ikenberg H, Gissmann L, Gross G, Grussendorf-Conen EI, zur Hausen H (1983) Human papillomavirus type-16-related DNA in genital Bowen’s disease and in bowenoid papulosis. Int J Cancer 32(5):563–565PubMedCrossRefGoogle Scholar
  42. 42.
    Kaye V, Zhang G, Dehner LP, Fraley EE (1990) Carcinoma in situ of penis. Is distinction between erythroplasia of queyrat and Bowen’s disease relevant? Urology 36(6):479–482PubMedCrossRefGoogle Scholar
  43. 43.
    von Krogh G, Horenblas SN (2000) Diagnosis and clinical presentation of premalignant lesions of the penis. Scand J Urol Nephrol 34:201–214CrossRefGoogle Scholar
  44. 44.
    Obalek S, Jablonska S, Beaudenon S, Walczak L, Orth G (1986) Bowenoid papulosis of the Male and Female Genitalia: Risk of Cervical Neoplasia. J Am Acad Dermatol 14(3):433–444PubMedCrossRefGoogle Scholar
  45. 45.
    Ammin BA, Tamboli P, Cubilla AL (2003) Penis and Scrotum. In: Weidner N, Cote RJ, Suster S, Weiss LM (eds) Modern surgical pathology. Elsevier Science, Philadelphia, pp 1197–1214Google Scholar
  46. 46.
    Barrasso R (1997) Latent and subclinical HPV external anogenital infection. Clin Dermatol 15(3):349–353PubMedCrossRefGoogle Scholar
  47. 47.
    Hippelainen M, Yliskoski M, Saarikoski S, Syrjanen S, Syrjanen K (1991) Genital human papillomavirus lesions of the male sexual partners: the diagnostic accuracy of peniscopy (see comments). Genitourin Med 67(4):291–296PubMedGoogle Scholar
  48. 48.
    Bleeker MC, Hogewoning CJ, van den Brule AJ, Voorhorst FJ, Van Andel RE, Risse EK, Starink TM, Meijer CJ (2002) Penile lesions and human papillomavirus in male sexual partners of women with cervical intraepithelial neoplasia. J Am Acad Dermatol 47(3):351–357PubMedCrossRefGoogle Scholar
  49. 49.
    Bleeker MC, Snijders PF, Voorhorst FJ, Meijer CJ (2006) Flat penile lesions: the infectious “Invisible” link in the transmission of human papillomavirus. Int J Cancer 119(11):2505–2512PubMedCrossRefGoogle Scholar
  50. 50.
    Kataoka A, Claesson U, Hansson BG, Eriksson M, Lindh E (1991) Human papillomavirus infection of the male diagnosed by Southern-blot hybridization and polymerase chain reaction: comparison between urethra samples and penile biopsy samples. J Med Virol 33(3):159–164PubMedCrossRefGoogle Scholar
  51. 51.
    Hippelainen M, Syrjanen S, Hippelainen M, Koskela H, Pulkkinen J, Saarikoski S, Syrjanen K (1993) Prevalence and risk factors of genital human papillomavirus (HPV) infections in healthy males: a study on Finnish Conscripts. Sex Transm Dis 20(6):321–328PubMedCrossRefGoogle Scholar
  52. 52.
    Chu QD, Vezeridis MP, Libbey NP, Wanebo HJ (1994) Giant condyloma acuminatum (Buschke–Lowenstein tumor) of the anorectal and perianal regions. analysis of 42 cases. Dis Colon Rectum 37(9):950–957PubMedCrossRefGoogle Scholar
  53. 53.
    Trombetta LJ, Place RJ (2001) Giant condyloma acuminatum of the anorectum: trends in epidemiology and management: report of a case and review of the literature. Dis Colon Rectum 44(12):1878–1886PubMedCrossRefGoogle Scholar
  54. 54.
    Grussendorf-Conen EI (1997) Anogenital premalignant and malignant Tumors (including Buschke–Lowenstein tumors). Clin Dermatol 15(3):377–388PubMedCrossRefGoogle Scholar
  55. 55.
    Powell JJ, Wojnarowska F (1999) Lichen sclerosus. Lancet 353(9166):1777–1783PubMedCrossRefGoogle Scholar
  56. 56.
    Meffert JJ, Davis BM, Grimwood RE (1995) Lichen sclerosus. J Am Acad Dermatol 32(3):393–416PubMedCrossRefGoogle Scholar
  57. 57.
    Velazquez EF, Cubilla AL (2003) Lichen sclerosus in 68 patients with squamous cell carcinoma of the penis: frequent atypias and correlation with special carcinoma variants suggests a precancerous role. Am J Surg Pathol 27(11):1448–1453PubMedCrossRefGoogle Scholar
  58. 58.
    Carli P, Cattaneo A, De Magnis A, Biggeri A, Taddei G, Giannotti B (1995) Squamous cell carcinoma arising in vulval lichen sclerosus: a longitudinal cohort study. Eur J Cancer Prev 4(6):491–495PubMedCrossRefGoogle Scholar
  59. 59.
    Perceau G, Derancourt C, Clavel C, Durlach A, Pluot M, Lardennois B, Bernard P (2003) Lichen sclerosus is frequently present in penile squamous cell carcinomas but is not always associated with oncogenic human papillomavirus. Br J Dermatol 148(5):934–938PubMedCrossRefGoogle Scholar
  60. 60.
    Powell J, Robson A, Cranston D, Wojnarowska F, Turner R (2001) High incidence of lichen sclerosus in patients with squamous cell carcinoma of the penis. Br J Dermatol 145(1):85–89PubMedCrossRefGoogle Scholar
  61. 61.
    Nasca MR, Innocenzi D, Micali G (1999) Penile cancer among patients with genital lichen sclerosus. J Am Acad Dermatol 41(6):911–914PubMedCrossRefGoogle Scholar
  62. 62.
    Nasca MR, Innocenzi D, Micali G (2006) Association of penile lichen sclerosus and oncogenic human papillomavirus infection. Int J Dermatol 45(6):681–683PubMedCrossRefGoogle Scholar
  63. 63.
    Snijders PJ, Steenbergen RD, Heideman DA, Meijer CJ (2006) HPV-mediated cervical carcinogenesis: concepts and clinical implications. J Pathol 208(2):152–164PubMedCrossRefGoogle Scholar
  64. 64.
    zur Hausen H (2002) Papillomaviruses and cancer: from basic studies to clinical application. Nat Rev Cancer 2(5):342–350PubMedCrossRefGoogle Scholar
  65. 65.
    Scheffner M, Romanczuk H, Munger K, Huibregtse JM, Mietz JA, Howley PM (1994) Functions of human papillomavirus proteins. Curr Top Microbiol Immunol 186:83–99PubMedGoogle Scholar
  66. 66.
    Steenbergen RD, Kramer D, Meijer CJ, Walboomers JM, Trott DA, Cuthbert AP, Newbold RF, Overkamp WJ, Zdzienicka MZ, Snijders PJ (2001) Telomerase suppression by chromosome 6 in a human papillomavirus type 16-immortalized keratinocyte cell line and in a cervical cancer cell line. J Natl Cancer Inst 93(11):865–872PubMedCrossRefGoogle Scholar
  67. 67.
    Franceschi S, Castellsague X, Dal Maso L, Smith JS, Plummer M, Ngelangel C, Chichareon S, Eluf-Neto J, Shah KV, Snijders PJ, Meijer CJ, Bosch FX, Munoz N (2002) Prevalence and determinants of human papillomavirus genital infection in men. Br J Cancer 86(5):705–711PubMedCrossRefGoogle Scholar
  68. 68.
    Bleeker MC, Hogewoning CJ, Berkhof J, Voorhorst FJ, Hesselink AT, van Diemen PM, van den Brule AJ, Snijders PJ, Meijer CJ (2005) Concordance of specific human papillomavirus types in sex partners is more prevalent than would be expected by chance and is associated with increased viral loads. Clin Infect Dis 41(5):612–620PubMedCrossRefGoogle Scholar
  69. 69.
    Martins AC, Faria SM, Cologna AJ, Suaid HJ, Tucci S Jr (2002) Immunoexpression of P53 protein and proliferating cell nuclear antigen in penile carcinoma. J Urol 167(1):89–92PubMedCrossRefGoogle Scholar
  70. 70.
    Scinicariello F, Rady P, Hannigan E, Dinh TV, Tyring SK (1992) Human papillomavirus type 16 found in primary transitional cell carcinoma of the bartholin’s gland and in a lymph node metastasis. Gynecol Oncol 47(2):263–266PubMedCrossRefGoogle Scholar
  71. 71.
    Leis PF, Stevens KR, Baer SC, Kadmon D, Goldberg LH, Wang XJ (1998) AC-RasHa mutation in the metastasis of a human papillomavirus (HPV)-18 positive penile squamous cell carcinoma suggests a cooperative effect between HPV-18 and C-RasHa activation in malignant progression. Cancer 83(1):122–129PubMedCrossRefGoogle Scholar
  72. 72.
    Couturier J, Sastre-Garau X, Schneider-Maunoury S, Labib A, Orth G (1991) Integration of papillomavirus DNA near Myc genes in genital carcinomas and its consequences for proto-oncogene Expression. J Virol 65(8):4534–4538PubMedGoogle Scholar
  73. 73.
    Sastre-Garau X, Favre M, Couturier J, Orth G (2000) Distinct patterns of alteration of myc genes associated with integration of human papillomavirus type 16 or type 45 DNA in two genital tumours. J Gen Virol 81(Pt 8):1983–1993PubMedGoogle Scholar
  74. 74.
    Campos RS, Lopes A, Guimaraes GC, Carvalho AL, Soares FA (2006) E-Cadherin, MMP-2, and MMP-9 as prognostic markers in penile cancer: analysis of 125 patients. Urology 67(4):797–802PubMedCrossRefGoogle Scholar
  75. 75.
    Golijanin D, Tan JY, Kazior A, Cohen EG, Russo P, Dalbagni G, Auborn KJ, Subbaramaiah K, Dannenberg AJ (2004) Cyclooxygenase-2 and microsomal prostaglandin E synthase-1 are overexpressed in squamous cell carcinoma of the penis. Clin Cancer Res 10(3):1024–1031PubMedCrossRefGoogle Scholar
  76. 76.
    Kayes O, Ahmed HU, Arya M, Minhas S (2007) Molecular and genetic pathways in penile cancer. Lancet Oncol 8(5):420–429PubMedCrossRefGoogle Scholar
  77. 77.
    Soufir N, Queille S, Liboutet M, Thibaudeau O, Bachelier F, Delestaing G, Balloy BC, Breuer J, Janin A, Dubertret L, Vilmer C, Basset-Seguin N (2007) Inactivation of the CDKN2A and the P53 tumour suppressor genes in external genital carcinomas and their precursors. Br J Dermatol 156(3):448–453PubMedCrossRefGoogle Scholar
  78. 78.
    Castren K, Vahakangas K, Heikkinen E, Ranki A (1998) Absence of P53 mutations in benign and pre-malignant male genital lesions with over-expressed P53 protein. Int J Cancer 77(5):674–678PubMedCrossRefGoogle Scholar
  79. 79.
    Pilotti S, Donghi R, D’Amato L, Giarola M, Longoni A, Della Torre G, De Palo G, Pierotti MA, Rilke F (1993) HPV detection and P53 alteration in squamous cell verrucous malignancies of the lower genital tract. Diagn Mol Pathol 2(4):248–256PubMedGoogle Scholar
  80. 80.
    Ranki A, Lassus J, Niemi KM (1995) Relation of P53 tumor suppressor protein expression to human papillomavirus (HPV) DNA and to cellular atypia in male genital warts and in premalignant lesions. Acta Derm Venereol 75(3):180–186PubMedGoogle Scholar
  81. 81.
    Castellsague X, Bosch FX, Munoz N, Meijer CJ, Shah KV, de Sanjose S, Eluf-Neto J, Ngelangel CA, Chichareon S, Smith JS, Herrero R, Moreno V, Franceschi S (2002) Male circumcision, penile human papillomavirus infection, and cervical cancer in female partners. N Engl J Med 346(15):1105–1112PubMedCrossRefGoogle Scholar
  82. 82.
    Vaccarella S, Lazcano-Ponce E, Castro-Garduno JA, Cruz-Valdez A, Diaz V, Schiavon R, Hernandez P, Kornegay JR, Hernandez-Avila M, Franceschi S (2006) Prevalence and determinants of human papillomavirus infection in men attending vasectomy clinics in Mexico. Int J Cancer 119(8):1934–1939PubMedCrossRefGoogle Scholar
  83. 83.
    Levine RU, Crum CP, Herman E, Silvers D, Ferenczy A, Richart RM (1984) Cervical papillomavirus infection and intraepithelial neoplasia: a study of male sexual partners. Obstet Gynecol 64(1):16–20PubMedGoogle Scholar
  84. 84.
    Bleeker MC, Hogewoning CJ, Voorhorst FJ, van den Brule AJ, Berkhof J, Hesselink AT, Lettink M, Starink TM, Stoof TJ, Snijders PJ, Meijer CJ (2005) HPV-associated flat penile lesions in men of a non-STD hospital population: less frequent and smaller in size than in male sexual partners of women with CIN. Int J Cancer 113(1):36–41PubMedCrossRefGoogle Scholar
  85. 85.
    Schoen EJ, Colby CJ, To TT (2006) Cost analysis of neonatal circumcision in a large health maintenance organization. J Urol 175(3 Pt 1):1111–1115PubMedCrossRefGoogle Scholar
  86. 86.
    Van Howe RS (1999) Does circumcision influence sexually transmitted diseases? A literature review. BJU Int 83(Suppl 1):52–62PubMedCrossRefGoogle Scholar
  87. 87.
    Siegfried N, Muller M, Deeks J, Volmink J, Egger M, Low N, Walker S, Williamson P (2005) HIV and male circumcision—a systematic review with assessment of the quality of studies. Lancet Infect Dis 5(3):165–173PubMedGoogle Scholar
  88. 88.
    Harper DM, Franco EL, Wheeler CM, Moscicki AB, Romanowski B, Roteli-Martins CM, Jenkins D, Schuind A, Costa Clemens SA, Dubin G (2006) Sustained efficacy up to 4.5 years of a bivalent L1 virus-like particle vaccine against human papillomavirus types 16 and 18: follow-up from a randomised control trial. Lancet 367(9518):1247–1255PubMedCrossRefGoogle Scholar
  89. 89.
    Harper DM, Franco EL, Wheeler C, Ferris DG, Jenkins D, Schuind A, Zahaf T, Innis B, Naud P, De Carvalho NS, Roteli-Martins CM, Teixeira J, Blatter MM, Korn AP, Quint W, Dubin G (2004) Efficacy of a bivalent L1 virus-like particle vaccine in prevention of infection with human papillomavirus types 16 and 18 in young women: a randomised controlled trial. Lancet 364(9447):1757–1765PubMedCrossRefGoogle Scholar
  90. 90.
    Villa LL, Costa RL, Petta CA, Andrade RP, Ault KA, Giuliano AR, Wheeler CM, Koutsky LA, Malm C, Lehtinen M, Skjeldestad FE, Olsson SE, Steinwall M, Brown DR, Kurman RJ, Ronnett BM, Stoler MH, Ferenczy A, Harper DM, Tamms GM, Yu J, Lupinacci L, Railkar R, Taddeo FJ, Jansen KU, Esser MT, Sings HL, Saah AJ, Barr E (2005) Prophylactic Quadrivalent Human Papillomavirus (Types 6, 11, 16, and 18) L1 virus-like particle vaccine in young women: a randomised double-blind placebo-controlled multicentre phase II efficacy trial. Lancet Oncol 6(5):271–278PubMedCrossRefGoogle Scholar
  91. 91.
    Garland SM, Hernandez-Avila M, Wheeler CM, Perez G, Harper DM, Leodolter S, Tang GW, Ferris DG, Steben M, Bryan J, Taddeo FJ, Railkar R, Esser MT, Sings HL, Nelson M, Boslego J, Sattler C, Barr E, Koutsky LA (2007) Quadrivalent vaccine against human papillomavirus to prevent anogenital diseases. N Engl J Med 356(19):1928–1943PubMedCrossRefGoogle Scholar
  92. 92.
    Block SL, Nolan T, Sattler C, Barr E, Giacoletti KE, Marchant CD, Castellsague X, Rusche SA, Lukac S, Bryan JT, Cavanaugh PF Jr, Reisinger KS (2006) Comparison of the immunogenicity and reactogenicity of a prophylactic quadrivalent human papillomavirus (types 6, 11, 16, and 18) L1 virus-like particle vaccine in male and female adolescents and young adult women. Pediatrics 118(5):2135–2145PubMedCrossRefGoogle Scholar
  93. 93.
    Garnett GP (2005) Role of herd immunity in determining the effect of vaccines against sexually transmitted disease. J Infect Dis 191(Suppl 1):S97–S106PubMedCrossRefGoogle Scholar
  94. 94.
    Holmes KK, Levine R, Weaver M (2004) Effectiveness of condoms in preventing sexually transmitted infections. Bull World Health Organ 82(6):454–461PubMedGoogle Scholar
  95. 95.
    Vaccarella S, Franceschi S, Herrero R, Munoz N, Snijders PJ, Clifford GM, Smith JS, Lazcano-Ponce E, Sukvirach S, Shin HR, de Sanjose S, Molano M, Matos E, Ferreccio C, Anh PT, Thomas JO, Meijer CJ (2006) Sexual behavior, condom use, and human papillomavirus: pooled analysis of the IARC human papillomavirus prevalence surveys. Cancer Epidemiol Biomarkers Prev 15(2):326–333PubMedCrossRefGoogle Scholar
  96. 96.
    Nielson CM, Harris RB, Dunne EF, Abrahamsen M, Papenfuss MR, Flores R, Markowitz LE, Giuliano AR (2007) Risk factors for anogenital human papillomavirus infection in men. J Infect Dis 196(8):1137–1145PubMedCrossRefGoogle Scholar
  97. 97.
    Winer RL, Hughes JP, Feng Q, O’Reilly S, Kiviat NB, Holmes KK, Koutsky LA (2006) Condom use and the risk of genital human papillomavirus infection in young women. N Engl J Med 354(25):2645–2654PubMedCrossRefGoogle Scholar
  98. 98.
    Hogewoning CJ, Bleeker MC, van den Brule AJ, Voorhorst FJ, Snijders PJ, Berkhof J, Westenend PJ, Meijer CJ (2003) Condom use promotes regression of cervical intraepithelial neoplasia and clearance of human papillomavirus: a randomized clinical trial. Int J Cancer 107(5):811–816PubMedCrossRefGoogle Scholar
  99. 99.
    Bleeker MC, Hogewoning CJ, Voorhorst FJ, van den Brule AJ, Snijders PJ, Starink TM, Berkhof J, Meijer CJ (2003) Condom use promotes regression of human papillomavirus-associated penile lesions in male sexual partners of women with cervical intraepithelial neoplasia. Int J Cancer 107(5):804–810PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • M. C. G. Bleeker
    • 1
  • D. A. M. Heideman
    • 1
  • P. J. F. Snijders
    • 1
  • S. Horenblas
    • 2
  • J. Dillner
    • 3
  • C. J. L. M. Meijer
    • 1
  1. 1.Department of PathologyVU University Medical CenterAmsterdamThe Netherlands
  2. 2.Department of UrologyThe Netherlands Cancer Institute, Antoni van Leeuwenhoek HospitalAmsterdamThe Netherlands
  3. 3.Department of Medical MicrobiologyLund University, University HospitalMalmöSweden

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