Current Oncology Reports

, 16:402 | Cite as

The Burden of HPV-Associated Anogenital Cancers

  • Katie WakehamEmail author
  • Kimberley Kavanagh
Gynecologic Cancers (NS Reed, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Gynecologic Cancers


The epidemiology of anogenital cancers is under going substantial change. Cervical cancer remains a major public health concern, particular in resource-limited settings. Cancers of the anus, penis, vagina and vulva are relatively uncommon cancers, but may be increasing in incidence. The change in occurrence of anogenital cancers may be due to increasing HPV transmission secondary to changes in sexual behaviour. Screening programmes and the HPV vaccine offer optimism that anogenital cancers can be prevented. This article reviews the epidemiology of anogenital cancers with a focus on Scottish data.


Human papillomavirus Cervical cancers Anal cancer Penile cancer Vaginal cancer Vulvar cancer 



The authors acknowledge Doug Clark of NHS National Services Scotland for preparation of the Scottish Cancer Registry data presented in this article.

Compliance with Ethics Guidelines

Conflict of Interest

Katie Wakeham and Kimberley Kavanagh declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


  1. 1.
    International Agency for Research on Cancer. GLOBOCAN 2012. In: Cervical cancer estimated incidence, mortality and prevalence worldwide in 2012. Accessed 4 May 2014.
  2. 2.
    McCredie MR et al. Natural history of cervical neoplasia and risk of invasive cancer in women with cervical intraepithelial neoplasia 3: a retrospective cohort study. Lancet Oncol. 2006;9(5):425–34.Google Scholar
  3. 3.
    Parkin DM, Bray F. Chapter  2: the burden of HPV-related cancers. Vaccine. 2006;24 Suppl 3:S11–25.Google Scholar
  4. 4.
    International Collaboration of Epidemiological Studies of Cervical Cancer. Comparison of risk factors for invasive squamous cell carcinoma and adenocarcinoma of the cervix: collaborative reanalysis of individual data on 8,097 women with squamous cell carcinoma and 1,374 women with adenocarcinoma from 12 epidemiological studies. Int J Cancer. 2007;120:885–90.Google Scholar
  5. 5.
    International Collaboration of Epidemiological Studies of Cervical Cancer. Carcinoma of the cervix and tobacco smoking: collaborative reanalysis of individual data on 13,541 women with carcinoma of the cervix and 23,017 women without carcinoma of the cervix from 23 epidemiological studies. Int J Cancer. 2006;118(6):1481–95.CrossRefGoogle Scholar
  6. 6.
    Wallin KL et al. A population-based prospective study of Chlamydia trachomatis infection and cervical carcinoma. Int J Cancer. 2002;101:371–4.Google Scholar
  7. 7.
    Palefsky JM. Cervical human papillomavirus infection and cervical intraepithelial neoplasia in women positive for human immunodeficiency virus in the era of highly active antiretroviral therapy. Curr Opin Oncol. 2003;15(5):382–8.PubMedCrossRefGoogle Scholar
  8. 8.
    Castellsague X et al. Male circumcision, penile human papillomavirus infection, and cervical cancer in female partners. N Engl J Med. 2002;346:1105–12.Google Scholar
  9. 9.
    International Agency for Research on Cancer. World Cancer Report 2008. Accessed on 4 May 2014.
  10. 10.
    Information Service Division, Scotland. Cancer incidence and mortality in Scotland by site/type of cancer, sex and year of diagnosis/registration of death: 2002-2011. Accessed 4 May 2014.
  11. 11.
    Information Service Division, Scotland. Scottish Cervical Screening Programme. Accessed on 4 May 2014.
  12. 12.
    Hill GB, Adelstein AM. Cohort mortality from carcinoma of the cervix. Lancet. 1967;2(7516):605–6.PubMedCrossRefGoogle Scholar
  13. 13.
    Bray F et al. Incidence trends of adenocarcinoma of the cervix in 13 European countries. Cancer Epidemiol Biomarkers Prev. 2005;14(9):2191–9.PubMedCrossRefGoogle Scholar
  14. 14.
    Bray F et al. Trends in cervical squamous cell carcinoma incidence in 13 European countries: changing risk and the effects of screening. Cancer Epidemiol Biomarkers Prev. 2005;14(3):677–86.Google Scholar
  15. 15.
    Sankaranarayanan R et al. An overview of cancer survival in Africa, Asia, the Caribbean and Central America: the case for investment in cancer health services. IARC Sci Publ. 2011;162:257–91.PubMedGoogle Scholar
  16. 16.
    Quinn MA et al. Carcinoma of the cervix uteri. FIGO 26th annual report on the results of treatment in gynecological cancer. Int J Gynaecol Obstet. 2006;95 Suppl 1:S43–103.PubMedCrossRefGoogle Scholar
  17. 17.
    Maranga IO et al. Analysis of factors contributing to the low survival of cervical cancer patients undergoing radiotherapy in Kenya. PLoS One. 2013;8(10):e78411.PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Siegel R et al. Cancer statistics, 2014. CA Cancer J Clin. 2014;64:9–29.PubMedCrossRefGoogle Scholar
  19. 19.
    Daling JR et al. Human papillomavirus, smoking, and sexual practices in the etiology of anal cancer. Cancer. 2004;101:270–80.PubMedCrossRefGoogle Scholar
  20. 20.
    Melbye M, Sprogel P. Aetiological parallel between anal cancer and cervical cancer. Lancet. 1991;338:657–9.PubMedCrossRefGoogle Scholar
  21. 21.
    Frisch M et al. Sexually transmitted infection as a cause of anal cancer. N Engl J Med. 1997;337(19):1350.PubMedCrossRefGoogle Scholar
  22. 22.
    Daling JR et al. Sexual practices, sexually transmitted diseases, and the incidence of anal cancer. N Engl J Med. 1987;317:973–7.PubMedCrossRefGoogle Scholar
  23. 23.
    Edgren G, Sparen P. Risk of anogenital cancer after diagnosis of cervical intraepithelial neoplasia: a prospective population-based study. Lancet Oncol. 2007;8:311–6.PubMedCrossRefGoogle Scholar
  24. 24.
    Rabkin CS et al. Second primary cancers following anal and cervical carcinoma: evidence of shared etiologic factors. Am J Epidemiol. 1992;136(1):54.PubMedGoogle Scholar
  25. 25.
    Frisch M et al. Malignancies that occur before and after anal cancer: clues to their etiology. Am J Epidemiol. 1994;140:12–9.PubMedGoogle Scholar
  26. 26.
    Holly EA et al. Anal cancer incidence: genital warts, anal fissure or fistula, hemorrhoids, and smoking. J Natl Cancer Inst. 1989;81:1726–31.PubMedCrossRefGoogle Scholar
  27. 27.
    Palefsky JM, Rubin M. The epidemiology of anal human papillomavirus and related neoplasia. Obstet Gynecol Clin N Am. 2009;36(1):187–200.CrossRefGoogle Scholar
  28. 28.
    Palefsky J. Human papillomavirus and anal neoplasia. Curr HIV/AIDS Rep. 2008;5:78–85.PubMedCrossRefGoogle Scholar
  29. 29.
    Silverberg MJ et al. Risk of anal cancer in HIV-infected and HIV-uninfected individuals in North America. Clin Infect Dis. 2012;54:1026–34.PubMedCentralPubMedCrossRefGoogle Scholar
  30. 30.
    Crum-Cianflone NF et al. Anal cancers among HIV-infected persons: HAART is not slowing rising incidence. AIDS. 2010;24:535–43.PubMedCentralPubMedCrossRefGoogle Scholar
  31. 31.
    Bower M et al. HIV-associated anal cancer: has highly active antiretroviral therapy reduced the incidence or improved the outcome? J Acquir Immune Defic Syndr. 2004;37:1563–5.PubMedCrossRefGoogle Scholar
  32. 32.
    Diamond C et al. Increased incidence of squamous cell anal cancer among men with AIDS in the era of highly active antiretroviral therapy. Sex Transm Dis. 2005;32:314–20.PubMedCrossRefGoogle Scholar
  33. 33.
    Sunesen KG et al. Immunosuppressive disorders and risk of anal squamous cell carcinoma: a nationwide cohort study in Denmark, 1978-2005. Int J Cancer. 2010;127:675–84.PubMedCrossRefGoogle Scholar
  34. 34.
    Adami J et al. Cancer risk following organ transplantation: a nationwide cohort study in Sweden. Br J Cancer. 2003;89(7):1221–7.PubMedCentralPubMedCrossRefGoogle Scholar
  35. 35.
    Johnson LG et al. Anal cancer incidence and survival: the surveillance, epidemiology, and end results experience, 1973-2000. Cancer. 2004;101:281–8.PubMedCrossRefGoogle Scholar
  36. 36.
    Brewster DH, Bhatti LA. Increasing incidence of squamous cell carcinoma of the anus in Scotland, 1975-2002. Br J Cancer. 2006;95:87–90.PubMedCentralPubMedCrossRefGoogle Scholar
  37. 37.
    Frisch M et al. Trends in incidence of anal cancer in Denmark. BMJ. 1993;306:419–22.PubMedCentralPubMedCrossRefGoogle Scholar
  38. 38.
    Jin F et al. Trends in anal cancer in Australia, 1982-2005. Vaccine. 2011;29:2322–7.PubMedCrossRefGoogle Scholar
  39. 39.
    Nielsen A et al. Trends in incidence of anal cancer and high-grade anal intraepithelial neoplasia in Denmark, 1978-2008. Int J Cancer. 2012;130:1168–73.PubMedCrossRefGoogle Scholar
  40. 40.
    Robinson D et al. An analysis of temporal and generational trends in the incidence of anal and other HPV-related cancers in southeast England. Br J Cancer. 2009;100:527–31.PubMedCentralPubMedCrossRefGoogle Scholar
  41. 41.
    Simard EP et al. Trends in the occurrence of high-grade anal intraepithelial neoplasia in San Francisco: 2000-2009. Cancer. 2013;119:3539–45.PubMedGoogle Scholar
  42. 42.
    Amirian ES et al. Anal cancer incidence and survival: comparing the greater San-Francisco bay area to other SEER cancer registries. PLoS One. 2013;8:e58919.PubMedCentralPubMedCrossRefGoogle Scholar
  43. 43.
    Gatta G et al. Survival from rare cancer in adults: a population-based study. Lancet Oncol. 2006;7:132–40.PubMedCrossRefGoogle Scholar
  44. 44.
    Hernandez BY et al. Burden of invasive squamous cell carcinoma of the penis in the United States, 1998-2003. Cancer. 2008;113:2883–91.PubMedCentralPubMedCrossRefGoogle Scholar
  45. 45.
    Ornellas AA. Management of penile cancer. J Surg Oncol. 2008;97(3):199–200.PubMedCrossRefGoogle Scholar
  46. 46.
    Maden C et al. History of circumcision, medical conditions, and sexual activity and risk of penile cancer. J Natl Cancer Inst. 1993;85:19–24.PubMedCrossRefGoogle Scholar
  47. 47.
    Daling JR et al. Penile cancer: importance of circumcision, human papillomavirus and smoking in in situ and invasive disease. Int J Cancer. 2005;116:606–16.PubMedCrossRefGoogle Scholar
  48. 48.
    Engels EA et al. Trends in cancer risk among people with AIDS in the United States 1980-2002. AIDS. 2006;20:1645–54.PubMedCrossRefGoogle Scholar
  49. 49.
    Lajous M et al. Determinants of prevalence, acquisition, and persistence of human papillomavirus in healthy Mexican military men. Cancer Epidemiol Biomarkers Prev. 2005;14(7):1710–6.PubMedCrossRefGoogle Scholar
  50. 50.
    Bleeker MC et al. Penile lesions and human papillomavirus in male sexual partners of women with cervical intraepithelial neoplasia. J Am Acad Dermatol. 2002;47(3):351–7.PubMedCrossRefGoogle Scholar
  51. 51.
    Partridge JM et al. Genital human papillomavirus infection in men: incidence and risk factors in a cohort of university students. J Infect Dis. 2007;196(8):1128–36.PubMedCrossRefGoogle Scholar
  52. 52.
    Chokunonga E et al. Trends in the incidence of cancer in the black population of Harare, Zimbabwe 1991-2010. Int J Cancer. 2013;133:721–9.PubMedCrossRefGoogle Scholar
  53. 53.
    Wabinga HR et al. Trends in the incidence of cancer in Kampala, Uganda 1991-2010. Int J Cancer. 2014;135(2):432–9.Google Scholar
  54. 54.
    Wabinga HR et al. Trends in cancer incidence in Kyadondo County, Uganda, 1960-1997. Br J Cancer. 2000;82:1585–92.Google Scholar
  55. 55.
    Ficarra V et al. Prognostic factors in penile cancer. Urology. 2010;76(2 Suppl 1):S66.PubMedCrossRefGoogle Scholar
  56. 56.
    Bruni L, et al. Human papillomavirus and related diseases report. L'Hospitalet de Llobregat: ICO Information Centre on HPV and Cancer; 2014.Google Scholar
  57. 57.
    Daling JR et al. A population-based study of squamous cell vaginal cancer: HPV and cofactors. Gynecol Oncol. 2002;84:263–70.Google Scholar
  58. 58.
    Strander B et al. Long term risk of invasive cancer after treatment for cervical intraepithelial neoplasia grade 3: population based cohort study. BMJ. 2007;335:1077.PubMedCentralPubMedCrossRefGoogle Scholar
  59. 59.
    Engels EA et al. Spectrum of cancer risk among US solid organ transplant recipients. JAMA. 2011;306:1891–901.Google Scholar
  60. 60.
    Gunderson CC, et al. A contemporary analysis of epidemiology and management of vaginal intraepithelial neoplasia. Am J Obstet Gynecol. 2013;208:410.e1–6.Google Scholar
  61. 61.
    Gunderson CC et al. Vaginal cancer: the experience from 2 large academic centers during a 15-year period. J Low Genit Tract Dis. 2013;17:409–13.Google Scholar
  62. 62.
    Cheng D et al. Wide local excision (WLE) for vaginal intraepithelial neoplasia (VAIN). Acta Obstet Gynecol Scand. 1999;78(7):648.Google Scholar
  63. 63.
    Aho M et al. Natural history of vaginal intraepithelial neoplasia. Cancer. 1991;68(1):195.Google Scholar
  64. 64.
    Hellman K et al. Clinical and histopathologic factors related to prognosis in primary squamous cell carcinoma of the vagina. Int J Gynecol Cancer. 2006;16:1201–11.Google Scholar
  65. 65.
    Tran PT et al. Prognostic factors for outcomes and complications for primary squamous cell carcinoma of the vagina treated with radiation. Gynecol Oncol. 2007;105:641–9.Google Scholar
  66. 66.
    Joura EA et al. Trends in vulvar neoplasia. Increasing incidence of vulvar intraepithelial neoplasia and squamous cell carcinoma of the vulva in young women. J Reprod Med. 2000;45:613–5.Google Scholar
  67. 67.
    Madsen BS et al. Risk factors for invasive squamous cell carcinoma of the vulva and vagina—population-based case-control study in Denmark. J Int Cancer. 2008;122:2827–34.Google Scholar
  68. 68.
    Jones RW et al. Trends in squamous cell carcinoma of the vulva: the influence of vulvar intraepithelial neoplasia. Obstet Gynecol. 1997;90:448–52.Google Scholar
  69. 69.
    Palefsky J. Human papillomavirus-related disease in people with HIV. Curr Opin HIV AIDS. 2009;4:52–6.Google Scholar
  70. 70.
    van Seters M et al. Is the assumed natural history of vulvar intraepithelial neoplasia III based on enough evidence? A systematic review of 3322 published patients. Gynecol Oncol. 2005;97:645–51.Google Scholar
  71. 71.
    Judson PL et al. Trends in the incidence of invasive and in situ vulvar carcinoma. Obstet Gynecol. 2006;107:1018–22.Google Scholar
  72. 72.
    Srodon M et al. The distribution of low and high-risk HPV types in vulvar and vaginal intraepithelial neoplasia (VIN and VaIN). Am J Surg Pathol. 2006;30:1513–8.Google Scholar
  73. 73.
    Conley LJ et al. HIV-1 infection and risk of vulvovaginal and perianal condylomata acuminata and intraepithelial neoplasia: a prospective cohort study. Lancet. 2002;359:108–13.Google Scholar
  74. 74.
    Burger MP et al. The importance of the groin node status for the survival of T1 and T2 vulval carcinoma patients. Gynecol Oncol. 1995;57:327–34.Google Scholar
  75. 75.
    Gadducci A et al. Old and new perspectives in the management of high-risk, locally advanced or recurrent, and metastatic vulvar cancer. Crit Rev Oncol Hematol. 2006;60:227–41.Google Scholar
  76. 76.
    International Agency for Research on Cancer, monographs on the evaluation of carcinogenic risk to humans, 2007. In: Monograph on human papillomavirus, volume 90. . Accessed 18 June 2014.
  77. 77.
    Clifford G et al. Chapter  3: HPV type-distribution in women with and without cervical neoplastic diseases. Vaccine. 2006;24 Suppl 3:S26–34.Google Scholar
  78. 78.
    De Vuyst H et al. Prevalence of human papillomavirus in women with invasive cervical carcinoma by HIV status in Kenya and South Africa. Int J Cancer. 2012;131:949–55.Google Scholar
  79. 79.
    Houlihan CF et al. Prevalence of human papillomavirus in adolescent girls before reported sexual debut. J Infect Dis. 2014. doi: 10.1093/infdis/jiu20.
  80. 80.
    Winer RL et al. Detection of genital HPV types in fingertip samples from newly sexually active female university students. Cancer Epidemiol Biomarkers Prev. 2010;19:1682–5.Google Scholar
  81. 81.
    af Geijersstam V et al. Trends in seroprevalence of human papillomavirus type 16 among pregnant women in Stockholm, Sweden, during 1969-1989. Int J Cancer. 1998;76:341–4.Google Scholar
  82. 82.
    Laukkanen P et al. Time trends in incidence and prevalence of human papillomavirus type 6, 11 and 16 infections in Finland. J Gen Virol. 2003;84:2105–9.Google Scholar
  83. 83.
    Mercer CH et al. Changes in sexual attitudes and lifestyles in Britain through the life course and over time: findings from the national surveys of sexual attitudes and lifestyles (Natsal). Lancet. 2013;382:1781–94.Google Scholar
  84. 84.
    Kangas I et al. A comparison of sexual behaviour and attitudes of healthy adolescents in a Danish high school in 1982, 1996, and 2001. Popul Health Metrics. 2004;2:5.Google Scholar
  85. 85.
    Winer RL et al. Condom use and the risk of genital human papillomavirus infection in young women. N Engl J Med. 2006;354:2645–54.Google Scholar
  86. 86.
    Gray RH et al. Male circumcision decreases acquisition and increases clearance of high-risk human papillomavirus in HIV-negative men: a randomized trial in Rakai, Uganda. J Infect Dis. 2010;201:1455–62.Google Scholar
  87. 87.
    Serwadda D et al. Circumcision of HIV-infected men: effects on high-risk human papillomavirus infections in a randomized trial in Rakai, Uganda. J Infect Dis. 2010;201:1463–9.Google Scholar
  88. 88.
    Kitchener HC et al. HPV testing in combination with liquid-based cytology in primary cervical screening (ARTISTIC): a randomised controlled trial. Lancet Oncol. 2009;10(7):672.Google Scholar
  89. 89.
    Ronco G et al. Efficacy of HPV-based screening for prevention of invasive cervical cancer: follow-up of four European randomised controlled trials. Lancet. 2014;383(9916):524.Google Scholar
  90. 90.
    Sankaranarayanan R et al. Effect of visual screening on cervical cancer incidence and mortality in Tamil Nadu, India: a cluster-randomised trial. Lancet. 2007;370:398–406.Google Scholar
  91. 91.
    Shastri SS et al. Concurrent evaluation of visual, cytological and HPV testing as screening methods for the early detection of cervical neoplasia in Mumbai, India. Bull World Health Organ. 2005;83:186–94.Google Scholar
  92. 92.
    Franco EL et al. Chapter  20: issues in planning cervical cancer screening in the era of HPV vaccination. Vaccine. 2006;24 Suppl 3:S171–7.Google Scholar
  93. 93.
    Smyczek P et al. Anal intraepithelial neoplasia: review and recommendations for screening and management. Int J STD AIDS. 2013;24(11):843–51.Google Scholar
  94. 94.
    FUTURE II Study Group. Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions. N Engl J Med. 2007;356(19):1915.CrossRefGoogle Scholar
  95. 95.
    Garland SM et al. Quadrivalent vaccine against human papillomavirus to prevent anogenital diseases. N Engl J Med. 2007;356(19):1928.Google Scholar
  96. 96.
    Malagon T et al. Cross-protective efficacy of two human papillomavirus vaccines: a systematic review and meta-analysis. Lancet Infect Dis. 2012;12:781–9.Google Scholar
  97. 97.
    Kavanagh K et al. Introduction and sustained high coverage of the HPV bivalent vaccine leads to a reduction in prevalence of HPV 16/18 and closely related HPV types. Br J Cancer. 2014;110:2804–11.Google Scholar
  98. 98.
    Palefsky JM et al. HPV vaccine against anal HPV infection and anal intraepithelial neoplasia. N Engl J Med. 2011;365:1576–85.Google Scholar
  99. 99.
    Wigle J et al. Human papillomavirus (HPV) vaccine implementation in low and middle-income countries (LMICs): health system experiences and prospects. Vaccine. 2013;31(37):3811–7.Google Scholar
  100. 100.
    Stanley M. HPV vaccination in boys and men. Hum Vaccin Immunother. 2014. doi: 10.4161/hv.29137.
  101. 101.
    The Scottish Parliament. Petitions, PE01477: Gender neutral Human Papillomavirus vaccination, 2013. Accessed 17 June 2014.

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Institute of Cancer SciencesUniversity of Glasgow, Garscube EstateGlasgowUK
  2. 2.Department of Mathematics and StatisticsUniversity of StrathclydeGlasgowUK

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