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Classification and epidemiology of anal cancer

David P Ryan, MD
Christopher G Willett, MD
Section Editor
Richard M Goldberg, MD
Deputy Editor
Diane MF Savarese, MD


Anal cancer is uncommon. It comprises only 2.5 percent of all digestive system malignancies in the United States; only 8200 new cases are diagnosed annually [1].

The incidence of anal cancer in the general population has increased over the last 30 years, both in the United States and elsewhere [2-6]. An increased incidence has been associated with female gender, infection with human papillomavirus (HPV), lifetime number of sexual partners, genital warts, cigarette smoking, receptive anal intercourse, and infection with human immunodeficiency virus (HIV) [7]. Thus, from an etiologic standpoint, anal cancer is more similar to genital malignancies than it is to gastrointestinal tract cancers.

Substantial progress has been made in the pathophysiology and treatment of anal cancer [8]. In the 1960s, this malignancy was thought to be due to chronic perianal inflammation and was treated routinely by abdominoperineal resection, necessitating a permanent colostomy [9]. As a result of carefully conducted epidemiologic and clinical studies, it is now known that anal cancer is associated with HPV infection and that cure of anal cancer is possible in the majority of patients with preservation of the anal sphincter.

The pathology and epidemiology of anal cancer will be reviewed here. The clinical features, diagnosis, and treatment are discussed separately. (See "Clinical features, staging, and treatment of anal cancer".)


The anal canal is 2.5 to 3.5 cm long. It begins where the rectum enters the puborectalis sling at the apex of the anal sphincter complex (palpable as the anorectal ring on digital rectal examination and approximately 1 to 2 cm proximal to the dentate line) and ends where the squamous mucosa blends with the perianal skin, which roughly coincides with the palpable intersphincteric groove or the outermost boundary of the internal sphincter muscle (figure 1). Externally, the anal canal is surrounded by the internal and external anal sphincter muscles (figure 1) [10]. The anal canal is divided by the dentate (pectinate) line, a macroscopically visible landmark that overlies the transition from glandular to squamous mucosa; immediately proximal to the dentate line, a narrow zone of transitional mucosa that is similar to urothelium is variably present.

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Literature review current through: Nov 2017. | This topic last updated: Nov 20, 2017.
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  1. Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin 2017; 67:7.
  2. Johnson LG, Madeleine MM, Newcomer LM, et al. Anal cancer incidence and survival: the surveillance, epidemiology, and end results experience, 1973-2000. Cancer 2004; 101:281.
  3. Chiao EY, Krown SE, Stier EA, Schrag D. A population-based analysis of temporal trends in the incidence of squamous anal canal cancer in relation to the HIV epidemic. J Acquir Immune Defic Syndr 2005; 40:451.
  4. Frisch M, Melbye M, Møller H. Trends in incidence of anal cancer in Denmark. BMJ 1993; 306:419.
  5. Brewster DH, Bhatti LA. Increasing incidence of squamous cell carcinoma of the anus in Scotland, 1975-2002. Br J Cancer 2006; 95:87.
  6. Goldman S, Glimelius B, Nilsson B, Påhlman L. Incidence of anal epidermoid carcinoma in Sweden 1970-1984. Acta Chir Scand 1989; 155:191.
  7. Palefsky JM. Anal human papillomavirus infection and anal cancer in HIV-positive individuals: an emerging problem. AIDS 1994; 8:283.
  8. Myerson RJ, Karnell LH, Menck HR. The National Cancer Data Base report on carcinoma of the anus. Cancer 1997; 80:805.
  9. Klotz RG Jr, Pamukcoglu T, Souilliard DH. Transitional cloacogenic carcinoma of the anal canal. Clinicopathologic study of three hundred seventy-three cases. Cancer 1967; 20:1727.
  10. Welton ML, Steele SR, Goodman KA, et al. Anus. In: AJCC Cancer Staging Manual, 8th ed, Amin MB (Ed), AJCC, Chicago 2017. p.275.
  11. Klas JV, Rothenberger DA, Wong WD, Madoff RD. Malignant tumors of the anal canal: the spectrum of disease, treatment, and outcomes. Cancer 1999; 85:1686.
  12. Flam M, John M, Pajak TF, et al. Role of mitomycin in combination with fluorouracil and radiotherapy, and of salvage chemoradiation in the definitive nonsurgical treatment of epidermoid carcinoma of the anal canal: results of a phase III randomized intergroup study. J Clin Oncol 1996; 14:2527.
  13. Bartelink H, Roelofsen F, Eschwege F, et al. Concomitant radiotherapy and chemotherapy is superior to radiotherapy alone in the treatment of locally advanced anal cancer: results of a phase III randomized trial of the European Organization for Research and Treatment of Cancer Radiotherapy and Gastrointestinal Cooperative Groups. J Clin Oncol 1997; 15:2040.
  14. American Joint Committee on Cancer Staging Manual, 7th, Edge SB, Byrd DR, Compton CC, et al (Eds), Springer, New York 2010. p.301.
  15. Frost DB, Richards PC, Montague ED, et al. Epidermoid cancer of the anorectum. Cancer 1984; 53:1285.
  16. Pintor MP, Northover JM, Nicholls RJ. Squamous cell carcinoma of the anus at one hospital from 1948 to 1984. Br J Surg 1989; 76:806.
  17. Greenall MJ, Quan SH, Stearns MW, et al. Epidermoid cancer of the anal margin. Pathologic features, treatment, and clinical results. Am J Surg 1985; 149:95.
  18. Robinson D, Coupland V, Møller H. 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.
  19. Shiels MS, Pfeiffer RM, Chaturvedi AK, et al. Impact of the HIV epidemic on the incidence rates of anal cancer in the United States. J Natl Cancer Inst 2012; 104:1591.
  20. Cook MB, Dawsey SM, Freedman ND, et al. Sex disparities in cancer incidence by period and age. Cancer Epidemiol Biomarkers Prev 2009; 18:1174.
  21. Islami F, Ferlay J, Lortet-Tieulent J, et al. International trends in anal cancer incidence rates. Int J Epidemiol 2016.
  22. Nelson RA, Levine AM, Bernstein L, et al. Changing patterns of anal canal carcinoma in the United States. J Clin Oncol 2013; 31:1569.
  23. Daling JR, Weiss NS, Klopfenstein LL, et al. Correlates of homosexual behavior and the incidence of anal cancer. JAMA 1982; 247:1988.
  24. Melbye M, Coté TR, Kessler L, et al. High incidence of anal cancer among AIDS patients. The AIDS/Cancer Working Group. Lancet 1994; 343:636.
  25. Goedert JJ, Coté TR, Virgo P, et al. Spectrum of AIDS-associated malignant disorders. Lancet 1998; 351:1833.
  26. Bower M, Powles T, Newsom-Davis T, 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.
  27. Diamond C, Taylor TH, Aboumrad T, 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.
  28. Cress RD, Holly EA. Incidence of anal cancer in California: increased incidence among men in San Francisco, 1973-1999. Prev Med 2003; 36:555.
  30. BUCKWALTER JA, JURAYJ MN. Relationship of chronic anorectal disease to carcinoma. AMA Arch Surg 1957; 75:352.
  31. Slater G, Greenstein A, Aufses AH Jr. Anal carcinoma in patients with Crohn's disease. Ann Surg 1984; 199:348.
  32. Daly JJ, Madrazo A. Anal Crohn's disease with carcinoma in situ. Dig Dis Sci 1980; 25:464.
  33. Holly EA, Whittemore AS, Aston DA, et al. Anal cancer incidence: genital warts, anal fissure or fistula, hemorrhoids, and smoking. J Natl Cancer Inst 1989; 81:1726.
  34. Frisch M, Olsen JH, Bautz A, Melbye M. Benign anal lesions and the risk of anal cancer. N Engl J Med 1994; 331:300.
  35. Frisch M, Johansen C. Anal carcinoma in inflammatory bowel disease. Br J Cancer 2000; 83:89.
  36. Peters RK, Mack TM. Patterns of anal carcinoma by gender and marital status in Los Angeles County. Br J Cancer 1983; 48:629.
  37. Daling JR, Weiss NS, Hislop TG, et al. Sexual practices, sexually transmitted diseases, and the incidence of anal cancer. N Engl J Med 1987; 317:973.
  38. Melbye M, Rabkin C, Frisch M, Biggar RJ. Changing patterns of anal cancer incidence in the United States, 1940-1989. Am J Epidemiol 1994; 139:772.
  39. Rabkin CS, Yellin F. Cancer incidence in a population with a high prevalence of infection with human immunodeficiency virus type 1. J Natl Cancer Inst 1994; 86:1711.
  40. Critchlow CW, Surawicz CM, Holmes KK, et al. Prospective study of high grade anal squamous intraepithelial neoplasia in a cohort of homosexual men: influence of HIV infection, immunosuppression and human papillomavirus infection. AIDS 1995; 9:1255.
  41. Frisch M, Glimelius B, van den Brule AJ, et al. Sexually transmitted infection as a cause of anal cancer. N Engl J Med 1997; 337:1350.
  42. Peters RK, Mack TM, Bernstein L. Parallels in the epidemiology of selected anogenital carcinomas. J Natl Cancer Inst 1984; 72:609.
  43. Melbye M, Sprøgel P. Aetiological parallel between anal cancer and cervical cancer. Lancet 1991; 338:657.
  44. Frisch M, Olsen JH, Melbye M. Malignancies that occur before and after anal cancer: clues to their etiology. Am J Epidemiol 1994; 140:12.
  45. Rabkin CS, Biggar RJ, Melbye M, Curtis RE. Second primary cancers following anal and cervical carcinoma: evidence of shared etiologic factors. Am J Epidemiol 1992; 136:54.
  46. Northfelt DW, Swift PS, Palefsky JM. Anal neoplasia. Pathogenesis, diagnosis, and management. Hematol Oncol Clin North Am 1996; 10:1177.
  47. Tilston P. Anal human papillomavirus and anal cancer. J Clin Pathol 1997; 50:625.
  48. Bjørge T, Engeland A, Luostarinen T, et al. Human papillomavirus infection as a risk factor for anal and perianal skin cancer in a prospective study. Br J Cancer 2002; 87:61.
  49. Daling JR, Madeleine MM, Johnson LG, et al. Human papillomavirus, smoking, and sexual practices in the etiology of anal cancer. Cancer 2004; 101:270.
  50. Joseph DA, Miller JW, Wu X, et al. Understanding the burden of human papillomavirus-associated anal cancers in the US. Cancer 2008; 113:2892.
  51. Serup-Hansen E, Linnemann D, Skovrider-Ruminski W, et al. Human papillomavirus genotyping and p16 expression as prognostic factors for patients with American Joint Committee on Cancer stages I to III carcinoma of the anal canal. J Clin Oncol 2014; 32:1812.
  52. Zaki SR, Judd R, Coffield LM, et al. Human papillomavirus infection and anal carcinoma. Retrospective analysis by in situ hybridization and the polymerase chain reaction. Am J Pathol 1992; 140:1345.
  53. Palefsky JM, Holly EA, Gonzales J, et al. Detection of human papillomavirus DNA in anal intraepithelial neoplasia and anal cancer. Cancer Res 1991; 51:1014.
  54. Duggan MA, Boras VF, Inoue M, et al. Human papillomavirus DNA determination of anal condylomata, dysplasias, and squamous carcinomas with in situ hybridization. Am J Clin Pathol 1989; 92:16.
  55. Palefsky JM, Holly EA, Hogeboom CJ, et al. Virologic, immunologic, and clinical parameters in the incidence and progression of anal squamous intraepithelial lesions in HIV-positive and HIV-negative homosexual men. J Acquir Immune Defic Syndr Hum Retrovirol 1998; 17:314.
  56. Machalek DA, Poynten M, Jin F, et al. Anal human papillomavirus infection and associated neoplastic lesions in men who have sex with men: a systematic review and meta-analysis. Lancet Oncol 2012; 13:487.
  57. Williams GR, Lu QL, Love SB, et al. Properties of HPV-positive and HPV-negative anal carcinomas. J Pathol 1996; 180:378.
  58. Palefsky JM, Giuliano AR, Goldstone S, et al. HPV vaccine against anal HPV infection and anal intraepithelial neoplasia. N Engl J Med 2011; 365:1576.
  59. Palefsky JM, Gonzales J, Greenblatt RM, et al. Anal intraepithelial neoplasia and anal papillomavirus infection among homosexual males with group IV HIV disease. JAMA 1990; 263:2911.
  60. Palefsky JM, Holly EA, Ralston ML, et al. Anal squamous intraepithelial lesions in HIV-positive and HIV-negative homosexual and bisexual men: prevalence and risk factors. J Acquir Immune Defic Syndr Hum Retrovirol 1998; 17:320.
  61. Palefsky JM, Holly EA, Ralston ML, et al. High incidence of anal high-grade squamous intra-epithelial lesions among HIV-positive and HIV-negative homosexual and bisexual men. AIDS 1998; 12:495.
  62. Silverberg MJ, Lau B, Justice AC, et al. Risk of anal cancer in HIV-infected and HIV-uninfected individuals in North America. Clin Infect Dis 2012; 54:1026.
  63. Frisch M, Biggar RJ, Goedert JJ. Human papillomavirus-associated cancers in patients with human immunodeficiency virus infection and acquired immunodeficiency syndrome. J Natl Cancer Inst 2000; 92:1500.
  64. Caussy D, Goedert JJ, Palefsky J, et al. Interaction of human immunodeficiency and papilloma viruses: association with anal epithelial abnormality in homosexual men. Int J Cancer 1990; 46:214.
  65. Kiviat N, Rompalo A, Bowden R, et al. Anal human papillomavirus infection among human immunodeficiency virus-seropositive and -seronegative men. J Infect Dis 1990; 162:358.
  66. Williams AB, Darragh TM, Vranizan K, et al. Anal and cervical human papillomavirus infection and risk of anal and cervical epithelial abnormalities in human immunodeficiency virus-infected women. Obstet Gynecol 1994; 83:205.
  67. Sun XW, Kuhn L, Ellerbrock TV, et al. Human papillomavirus infection in women infected with the human immunodeficiency virus. N Engl J Med 1997; 337:1343.
  68. Sobhani I, Vuagnat A, Walker F, et al. Prevalence of high-grade dysplasia and cancer in the anal canal in human papillomavirus-infected individuals. Gastroenterology 2001; 120:857.
  69. Biggar RJ, Burnett W, Mikl J, Nasca P. Cancer among New York men at risk of acquired immunodeficiency syndrome. Int J Cancer 1989; 43:979.
  70. Selik RM, Rabkin CS. Cancer death rates associated with human immunodeficiency virus infection in the United States. J Natl Cancer Inst 1998; 90:1300.
  71. Biggar RJ, Horm J, Goedert JJ, Melbye M. Cancer in a group at risk of acquired immunodeficiency syndrome (AIDS) through 1984. Am J Epidemiol 1987; 126:578.
  72. Harnly ME, Swan SH, Holly EA, et al. Temporal trends in the incidence of non-Hodgkin's lymphoma and selected malignancies in a population with a high incidence of acquired immunodeficiency syndrome (AIDS). Am J Epidemiol 1988; 128:261.
  73. Colón-López V, Shiels MS, Machin M, et al. Anal Cancer Risk Among People With HIV Infection in the United States. J Clin Oncol 2017; :JCO2017749291.
  74. Crum-Cianflone NF, Hullsiek KH, Marconi VC, et al. Anal cancers among HIV-infected persons: HAART is not slowing rising incidence. AIDS 2010; 24:535.
  75. Piketty C, Selinger-Leneman H, Bouvier AM, et al. Incidence of HIV-related anal cancer remains increased despite long-term combined antiretroviral treatment: results from the french hospital database on HIV. J Clin Oncol 2012; 30:4360.
  76. Palefsky JM, Holly EA, Ralston ML, Jay N. Prevalence and risk factors for human papillomavirus infection of the anal canal in human immunodeficiency virus (HIV)-positive and HIV-negative homosexual men. J Infect Dis 1998; 177:361.
  77. Unger ER, Vernon SD, Lee DR, et al. Human papillomavirus type in anal epithelial lesions is influenced by human immunodeficiency virus. Arch Pathol Lab Med 1997; 121:820.
  78. Bertisch B, Franceschi S, Lise M, et al. Risk factors for anal cancer in persons infected with HIV: a nested case-control study in the Swiss HIV Cohort Study. Am J Epidemiol 2013; 178:877.
  79. Penn I. Incidence and treatment of neoplasia after transplantation. J Heart Lung Transplant 1993; 12:S328.
  80. Penn I. Cancers of the anogenital region in renal transplant recipients. Analysis of 65 cases. Cancer 1986; 58:611.
  81. Arends MJ, Benton EC, McLaren KM, et al. Renal allograft recipients with high susceptibility to cutaneous malignancy have an increased prevalence of human papillomavirus DNA in skin tumours and a greater risk of anogenital malignancy. Br J Cancer 1997; 75:722.
  82. Sillman F, Stanek A, Sedlis A, et al. The relationship between human papillomavirus and lower genital intraepithelial neoplasia in immunosuppressed women. Am J Obstet Gynecol 1984; 150:300.
  83. Sillman FH, Sedlis A. Anogenital papillomavirus infection and neoplasia in immunodeficient women: an update. Dermatol Clin 1991; 9:353.
  84. Holmes F, Borek D, Owen-Kummer M, et al. Anal cancer in women. Gastroenterology 1988; 95:107.
  85. Daling JR, Sherman KJ, Hislop TG, et al. Cigarette smoking and the risk of anogenital cancer. Am J Epidemiol 1992; 135:180.
  86. Frisch M, Glimelius B, Wohlfahrt J, et al. Tobacco smoking as a risk factor in anal carcinoma: an antiestrogenic mechanism? J Natl Cancer Inst 1999; 91:708.
  87. Sood AK. Cigarette smoking and cervical cancer: meta-analysis and critical review of recent studies. Am J Prev Med 1991; 7:208.