Skip to main content
SpringerLink
Log in

Anal Cancer

  • Chapter
  • First Online:
Surgical Oncology Manual

  • 876 Accesses

Abstract

Anal cancer is an uncommon cancer, representing 2.5% of all GI malignancies, with increased incidence in immunosuppressed individuals and those with risk factors for HPV exposure. Precursor lesions include low-grade and high-grade squamous intraepithelial lesions (LSIL and HSIL); treatment of HSIL may prevent progression to cancer.

Anal cancer is subdivided into anal canal cancer or perianal cancer. The standard treatment for non-metastatic anal cancer is concurrent radiation and chemotherapy. Some favorable perianal lesions smaller than 2 cm can be excised. Otherwise, surgery plays a role in diagnosis and as a salvage treatment for persistent or recurrent local disease after chemoradiotherapy treatment. In selected cases negative microscopic surgical resection margins are achieved in up to 90% of cases, often with abdominoperineal resection with en bloc resection of adherent structures. For patients with metastatic disease, systemic therapy is the mainstay of treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 99.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 129.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Canadian Cancer Statistics Advisory Committee. Anal Cancer statistics. In: Can. Cancer Soc. 2013. http://www.cancer.ca/en/cancer-information/cancer-type/anal/statistics/?region=on. Accessed 11 Dec 2018.

  2. SEER Cancer Stat Facts: Anal Cancer. Natl Cancer Inst. 2018. https://seer.cancer.gov/statfacts/html/anus.html. Accessed 11 Dec 2018.

  3. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018 CA: a cancer. J Clin. 2017;68:7–30.

    Google Scholar 

  4. Van Dyne EA, Henley SJ, Saraiya M, Thomas CC, Markowitz LE, Benard VB. Trends in human papillomavirus–associated cancers—United States, 1999–2015. Morb Mortal Wkly Rep. 2018;67:918.

    Article  Google Scholar 

  5. Klas JV, Rothenberger DA, Wong WD, Madoff RD. Malignant tumors of the anal canal: the spectrum of disease, treatment, and outcomes. Cancer Interdiscip Int J Am Cancer Soc. 1999;85:1686–93.

    CAS  Google Scholar 

  6. Grulich AE, Van Leeuwen MT, Falster MO, Vajdic CM. Incidence of cancers in people with HIV/AIDS compared with immunosuppressed transplant recipients: a meta-analysis. Lancet. 2007;370:59–67.

    Article  PubMed  Google Scholar 

  7. Madeleine MM, Finch JL, Lynch CF, Goodman MT, Engels EA. HPV-related cancers after solid organ transplantation in the United States. Am J Transplant. 2013;13:3202–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Medford RJ, Salit IE. Anal cancer and intraepithelial neoplasia: epidemiology, screening and prevention of a sexually transmitted disease. Can Med Assoc J. 2015;187:111–5.

    Article  Google Scholar 

  9. Silverberg MJ, Lau B, Justice AC, Engels E, Gill MJ, Goedert JJ, Kirk GD, D’souza G, Bosch RJ, Brooks JT. Risk of anal cancer in HIV-infected and HIV-uninfected individuals in North America. Clin Infect Dis. 2012;54:1026–34.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Goligher JC, Leacock AG, Brossy J. The surgical anatomy of the anal canal. Br J Surg. 1955;43:51–61.

    Google Scholar 

  11. Amin MB, Edge S, Greene F, et al, editors. AJCC cancer staging manual. 8th ed. Switzerland: Springer International Publishing.

    Google Scholar 

  12. Longacre TA, Kong CS, Welton ML. Diagnostic problems in anal pathology. Adv Anat Pathol. 2008;15:263–78.

    Article  PubMed  Google Scholar 

  13. Glynne-Jones R, Nilsson PJ, Aschele C, Goh V, Peiffert D, Cervantes A, Arnold D. Anal cancer: ESMO-ESSO-ESTRO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2014;25:iii10–20.

    Article  PubMed  Google Scholar 

  14. Darragh TM, Colgan TJ, Cox JT, Heller DS, Henry MR, Luff RD, McCalmont T, Nayar R, Palefsky JM, Stoler MH. The lower anogenital squamous terminology standardization project for HPV-associated lesions: background and consensus recommendations from the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology. Arch Pathol Lab Med. 2012;136:1266–97.

    Article  PubMed  Google Scholar 

  15. Yang EJ, Kong CS, Longacre TA. Vulvar and anal intraepithelial neoplasia: terminology, diagnosis, and ancillary studies. Adv Anat Pathol. 2017;24:136–50.

    Article  PubMed  Google Scholar 

  16. Berry-Lawhorn JM, Palefsky JM. Progression of anal high-grade squamous intraepithelial lesions to anal squamous cell carcinoma and clinical management of anal superficially invasive squamous cell carcinoma. In: Semin. Colon Rectal Surg. Elsevier; 2017. p. 91–6.

    Google Scholar 

  17. De Vuyst H, Clifford GM, Nascimento MC, Madeleine MM, Franceschi S. Prevalence and type distribution of human papillomavirus in carcinoma and intraepithelial neoplasia of the vulva, vagina and anus: a meta-analysis. Int J Cancer. 2009;124:1626–36.

    Article  PubMed  CAS  Google Scholar 

  18. Saraiya M, Unger ER, Thompson TD, Lynch CF, Hernandez BY, Lyu CW, Steinau M, Watson M, Wilkinson EJ, Hopenhayn C. US assessment of HPV types in cancers: implications for current and 9-valent HPV vaccines. JNCI J Natl Cancer Inst. 2015;107(6):djv086.

    Article  PubMed  CAS  Google Scholar 

  19. Plummer M, de Martel C, Vignat J, Ferlay J, Bray F, Franceschi S. Global burden of cancers attributable to infections in 2012: a synthetic analysis. Lancet Glob Heal. 2016;4:e609–16.

    Article  Google Scholar 

  20. Salvadori MI. Human papillomavirus vaccine for children and adolescents. 2018.

    Google Scholar 

  21. Viarisio D, Gissmann L, Tommasino M. Human papillomaviruses and carcinogenesis: well-established and novel models. Curr Opin Virol. 2017;26:56–62.

    Article  CAS  PubMed  Google Scholar 

  22. Conley LJ, Ellerbrock TV, Bush TJ, Chiasson MA, Sawo D, Wright TC. HIV-1 infection and risk of vulvovaginal and perianal condylomata acuminata and intraepithelial neoplasia: a prospective cohort study. Lancet. 2002;359:108–13.

    Article  PubMed  Google Scholar 

  23. Rodríguez AC, Schiffman M, Herrero R, Wacholder S, Hildesheim A, Castle PE, Solomon D, Burk R, Group PEG. Rapid clearance of human papillomavirus and implications for clinical focus on persistent infections. J Natl Cancer Inst. 2008;100:513–7.

    Article  PubMed  Google Scholar 

  24. Frisch M, Olsen JH, Bautz A, Melbye M. Benign anal lesions and the risk of anal cancer. N Engl J Med. 1994;331:300–2.

    Article  CAS  PubMed  Google Scholar 

  25. Frisch M, Johansen C. Anal carcinoma in inflammatory bowel disease. Br J Cancer. 2000;83:89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Tseng H-F, Morgenstern H, Mack TM, Peters RK. Risk factors for anal cancer: results of a population-based case–control study. Cancer Causes Control. 2003;14:837–46.

    Article  PubMed  Google Scholar 

  27. Frisch M, Glimelius B, van den Brule AJC, Wohlfahrt J, Meijer CJLM, Walboomers JMM, Goldman S, Svensson C, Adami H-O, Melbye M. Sexually transmitted infection as a cause of anal cancer. N Engl J Med. 1997;337:1350–8.

    Article  CAS  PubMed  Google Scholar 

  28. Schwartz LM, Castle PE, Follansbee S, Borgonovo S, Fetterman B, Tokugawa D, Lorey TS, Sahasrabuddhe VV, Luhn P, Gage JC. Risk factors for anal HPV infection and anal precancer in HIV-infected men who have sex with men. J Infect Dis. 2013;208:1768–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Edgren G, Sparén P. Risk of anogenital cancer after diagnosis of cervical intraepithelial neoplasia: a prospective population-based study. Lancet Oncol. 2007;8:311–6.

    Article  PubMed  Google Scholar 

  30. Tong WWY, Hillman RJ, Kelleher AD, Grulich AE, Carr A. Anal intraepithelial neoplasia and squamous cell carcinoma in HIV-infected adults. HIV Med. 2014;15:65–76.

    Article  CAS  PubMed  Google Scholar 

  31. Sunesen KG, Nørgaard M, Thorlacius-Ussing O, Laurberg S. Immunosuppressive disorders and risk of anal squamous cell carcinoma: a nationwide cohort study in Denmark, 1978–2005. Int J Cancer. 2010;127:675–84.

    Article  CAS  PubMed  Google Scholar 

  32. Albuquerque A, Cappello C, Cuming T, De Masi A, Bowring J, Rosenthal AN, Nathan M. Anal high-grade squamous intraepithelial lesions in pharmacologically immunocompromised patients followed in a referral center. Dis Colon Rectum. 2018;61:1267–72.

    Article  PubMed  Google Scholar 

  33. Joseph DA, Miller JW, Wu X, Chen VW, Morris CR, Goodman MT, Villalon-Gomez JM, Williams MA, Cress RD. Understanding the burden of human papillomavirus-associated anal cancers in the US. Cancer. 2008;113:2892–900.

    Article  PubMed  Google Scholar 

  34. Daling JR, Madeleine MM, Johnson LG, Schwartz SM, Shera KA, Wurscher MA, Carter JJ, Porter PL, Galloway DA, McDougall JK. Human papillomavirus, smoking, and sexual practices in the etiology of anal cancer. Cancer. 2004;101:270–80.

    Article  PubMed  Google Scholar 

  35. Lee GC, Kunitake H, Milch H, Savitt LR, Stafford CE, Bordeianou LG, Francone TD, Ricciardi R. What is the risk of anal carcinoma in patients with anal intraepithelial neoplasia III? Dis Colon Rectum. 2018;61:1350–6.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Tong WWY, Jin F, McHugh LC, Maher T, Sinclair B, Grulich AE, Hillman RJ, Carr A. Progression to and spontaneous regression of high-grade anal squamous intraepithelial lesions in HIV-infected and uninfected men. AIDS. 2013;27:2233–43.

    Article  PubMed  Google Scholar 

  37. Tinmouth J, Peeva V, Amare H, Blitz S, Raboud J, Sano M, Steele L, Salit IE. Progression from perianal high-grade anal intraepithelial neoplasia to anal cancer in HIV-positive men who have sex with men. Dis Colon Rectum. 2016;59:836–42.

    Article  PubMed  Google Scholar 

  38. Fazendin EA, Crean AJ, Fazendin JM, Kucejko RJ, Gill HS, Poggio JL, Stein DE. Condyloma acuminatum, anal intraepithelial neoplasia, and anal cancer in the setting of HIV: do we really understand the risk? Dis Colon Rectum. 2017;60:1078–82.

    Article  PubMed  Google Scholar 

  39. Cajas-Monson LC, Ramamoorthy SL, Cosman BC. Expectant management of high-grade anal Dysplasia in people with HIV: long-term data. Dis Colon Rectum. 2018;61:1357–63.

    Article  PubMed  Google Scholar 

  40. Machalek DA, Poynten M, Jin F, Fairley CK, Farnsworth A, Garland SM, Hillman RJ, Petoumenos K, Roberts J, Tabrizi SN. Anal human papillomavirus infection and associated neoplastic lesions in men who have sex with men: a systematic review and meta-analysis. Lancet Oncol. 2012;13:487–500.

    Article  PubMed  Google Scholar 

  41. Tong WWY, Shepherd K, Garland S, Meagher A, Templeton DJ, Fairley CK, Jin F, Poynten IM, Zaunders J, Hillman RJ. Human papillomavirus 16–specific T-cell responses and spontaneous regression of anal high-grade squamous intraepithelial lesions. J Infect Dis. 2014;211:405–15.

    Article  PubMed  CAS  Google Scholar 

  42. Factor SH, Cooperstein A, Pereira GA, Goldstone SE. Are colon and rectal surgeons ready to screen for anal dysplasia? Results of a survey on attitudes and practice. Sex Transm Dis. 2014;41:246–53.

    Article  PubMed  Google Scholar 

  43. Alam NN, White DA, Narang SK, Daniels IR, Smart NJ. Systematic review of guidelines for the assessment and management of high-grade anal intraepithelial neoplasia (AIN II/III). Color Dis. 2016;18:135–46.

    Article  CAS  Google Scholar 

  44. Crawshaw BP, Russ AJ, Stein SL, Reynolds HL, Marderstein EL, Delaney CP, Champagne BJ. High-resolution anoscopy or expectant management for anal intraepithelial neoplasia for the prevention of anal cancer: is there really a difference? Dis Colon Rectum. 2015;58:53–9.

    Article  PubMed  Google Scholar 

  45. Goldstone SE. One step forward, two steps. Dis Colon Rectum. 2018;61:1339–41.

    Article  PubMed  Google Scholar 

  46. Topical or ablative treatment in preventing anal cancer in patients with HIV and anal high-grade squamous intraepithelial lesions (ANCHOR). In: (Identification No. NCT02135419). 2014. https://clinicaltrials.gov/ct2/show/NCT02135419. Accessed 14 Dec 2018.

  47. The HPV-SAVE Study Team: HPV screening and vaccine evaluation in men who have sex with men (HPV-SAVE). In: (Identification No. NCT02503111). 2015. https://clinicaltrials.gov/ct2/show/NCT02503111. Accessed 14 Dec 2018.

  48. Hillman RJ, Cuming T, Darragh T, Nathan M, Berry-Lawthorn M, Goldstone S, Law C, Palefsky J, Barroso LF, Stier EA. 2016 IANS international guidelines for practice standards in the detection of anal cancer precursors. J Low Genit Tract Dis. 2016;20:283–91.

    Article  PubMed  Google Scholar 

  49. Stockfleth E, Beti H, Orasan R, Grigorian F, Mescheder A, Tawfik H, Thielert C. Topical Polyphenon® E in the treatment of external genital and perianal warts: a randomized controlled trial. Br J Dermatol. 2008;158:1329–38.

    Article  CAS  PubMed  Google Scholar 

  50. Tyring S, Edwards L, Cherry LK, Ramsdell WM, Kotner S, Greenberg MD, Vance JC, Barnum G, Dromgoole SH, Killey FP. Safety and efficacy of 0.5% podofilox gel in the treatment of anogenital warts. Arch Dermatol. 1998;134:33–8.

    Article  CAS  PubMed  Google Scholar 

  51. Stewart DB, Gaertner WB, Glasgow SC, Herzig DO, Feingold D, Steele SR. The American society of colon and rectal surgeons clinical practice guidelines for anal squamous cell cancers (revised 2018). Dis Colon Rectum. 2018;61:755–74.

    Article  PubMed  Google Scholar 

  52. Fox PA, Nathan M, Francis N, Singh N, Weir J, Dixon G, Barton SE, Bower M. A double-blind, randomized controlled trial of the use of imiquimod cream for the treatment of anal canal high-grade anal intraepithelial neoplasia in HIV-positive MSM on HAART, with long-term follow-up data including the use of open-label imiquimod. AIDS. 2010;24:2331–5.

    Article  CAS  PubMed  Google Scholar 

  53. Richel O, de Vries HJC, van Noesel CJM, Dijkgraaf MGW, Prins JM. Comparison of imiquimod, topical fluorouracil, and electrocautery for the treatment of anal intraepithelial neoplasia in HIV-positive men who have sex with men: an open-label, randomised controlled trial. Lancet Oncol. 2013;14:346–53.

    Article  CAS  PubMed  Google Scholar 

  54. van der Snoek EM, den Hollander JC, van der Ende ME. Imiquimod 5% cream for five consecutive days a week in an HIV-infected observational cohort up to 32 weeks in the treatment of high-grade squamous intraepithelial lesions. Sex Transm Infect. 2015;91(4):245–7.

    Article  PubMed  Google Scholar 

  55. Richel O, Wieland U, De Vries HJC, Brockmeyer NH, Van Noesel C, Potthoff A, Prins JM, Kreuter A. Topical 5-fluorouracil treatment of anal intraepithelial neoplasia in human immunodeficiency virus-positive men. Br J Dermatol. 2010;163:1301–7.

    Article  CAS  PubMed  Google Scholar 

  56. Stier EA, Goldstone SE, Einstein MH, Jay N, Berry JM, Wilkin T, Lee JY, Darragh TM, Da Costa M, Panther L. Safety and efficacy of topical cidofovir to treat high-grade perianal and vulvar intraepithelial neoplasia in HIV-positive men and women. AIDS. 2013;27:545.

    Article  CAS  PubMed  Google Scholar 

  57. Sendagorta E, Bernardino JI, Álvarez-Gallego M, Feíto M, Feltes R, Beato MJ, Pérez-Molina JA, Yllescas M, Díaz-Almirón M, Arribas JR. Topical cidofovir to treat high-grade anal intraepithelial neoplasia in HIV-infected patients: a pilot clinical trial. AIDS. 2016;30:75–82.

    Article  CAS  PubMed  Google Scholar 

  58. Singh JC, Kuohung V, Palefsky JM. Efficacy of trichloroacetic acid in the treatment of anal intraepithelial neoplasia in HIV-positive and HIV-negative men who have sex with men. J Acquir Immune Defic Syndr. 2009;52:474.

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Cranston RD, Baker JR, Liu Y, Wang L, Elishaev E, Ho KS. Topical application of trichloroacetic acid is efficacious for the treatment of internal anal high-grade squamous intraepithelial lesions in HIV-positive men. Sex Transm Dis. 2014;41:420–6.

    Article  CAS  PubMed  Google Scholar 

  60. Marks DK, Goldstone SE. Electrocautery ablation of high-grade anal squamous intraepithelial lesions in HIV-negative and HIV-positive men who have sex with men. JAIDS J Acquir Immune Defic Syndr. 2012;59:259–65.

    Article  PubMed  Google Scholar 

  61. Pineda CE, Berry JM, Jay N, Palefsky JM, Welton ML. High-resolution anoscopy targeted surgical destruction of anal high-grade squamous intraepithelial lesions: a ten-year experience. Dis Colon Rectum. 2008;51:829–37.

    Article  PubMed  Google Scholar 

  62. Burgos J, Curran A, Landolfi S, Navarro J, Tallada N, Guelar A, Crespo M, Ocaña I, Ribera E, Falcó V. The effectiveness of electrocautery ablation for the treatment of high-grade anal intraepithelial neoplasia in HIV-infected men who have sex with men. HIV Med. 2016;17:524–31.

    Article  CAS  PubMed  Google Scholar 

  63. Goldstone RN, Hasan SR, Goldstone SE. Brief report: radiofrequency ablation therapy for anal intraepithelial neoplasia results from a single-center prospective pilot study in HIV+ participants. JAIDS J Acquir Immune Defic Syndr. 2017;76:e93–7.

    Article  PubMed  Google Scholar 

  64. Weis SE, Vecino I, Pogoda JM, Susa JS. Treatment of high-grade anal intraepithelial neoplasia with infrared coagulation in a primary care population of HIV-infected men and women. Dis Colon Rectum. 2012;55:1236–43.

    Article  PubMed  Google Scholar 

  65. Sirera G, Videla S, Piñol M, Coll J, García-Cuyás F, Vela S, Cañadas M, Darwich L, Pérez N, Gel S. Long-term effectiveness of infrared coagulation for the treatment of anal intraepithelial neoplasia grades 2 and 3 in HIV-infected men and women. AIDS. 2013;27:951–9.

    Article  CAS  PubMed  Google Scholar 

  66. Goldstone SE, Johnstone AA, Moshier EL. Long-term outcome of ablation of anal high-grade squamous intraepithelial lesions: recurrence and incidence of cancer. Dis Colon Rectum. 2014;57:316–23.

    Article  PubMed  Google Scholar 

  67. Steele SR, Varma MG, Melton GB, Ross HM, Rafferty JF, Buie WD. Practice parameters for anal squamous neoplasms. Dis Colon Rectum. 2012;55:735–49.

    Article  PubMed  Google Scholar 

  68. Shridhar R, Shibata D, Chan E, Thomas CR. Anal cancer: current standards in care and recent changes in practice. CA Cancer J Clin. 2015;65:139–62.

    Article  PubMed  Google Scholar 

  69. Goffredo P, Garancini M, Robinson TJ, Frakes J, Hoshi H, Hassan I. A national-level validation of the new American joint committee on cancer 8th edition subclassification of stage IIA and B anal squamous cell cancer. Ann Surg Oncol. 2018;25(6):1–7.

    Google Scholar 

  70. Gunderson LL, Moughan J, Ajani JA, Pedersen JE, Winter KA, Benson AB III, Thomas CR Jr, Mayer RJ, Haddock MG, Rich TA. Anal carcinoma: impact of TN category of disease on survival, disease relapse, and colostomy failure in US gastrointestinal intergroup RTOG 98-11 phase 3 trial. Int J Radiat Oncol Biol Phys. 2013;87:638–45.

    Article  PubMed  PubMed Central  Google Scholar 

  71. Glynne-Jones R, Kadalayil L, Meadows HM, Cunningham D, Samuel L, Geh JI, Lowdell C, James R, Beare S, Begum R. Tumour-and treatment-related colostomy rates following mitomycin C or cisplatin chemoradiation with or without maintenance chemotherapy in squamous cell carcinoma of the anus in the ACT II trial. Ann Oncol. 2014;25:1616–22.

    Article  CAS  PubMed  Google Scholar 

  72. Bilimoria KY, Bentrem DJ, Rock CE, Stewart AK, Ko CY, Halverson A. Outcomes and prognostic factors for squamous-cell carcinoma of the anal canal: analysis of patients from the National Cancer Data Base. Dis Colon Rectum. 2009;52:624–31.

    Article  PubMed  Google Scholar 

  73. Jones CM, Goh V, Sebag-Montefiore D, Gilbert DC. Biomarkers in anal cancer: from biological understanding to stratified treatment. Br J Cancer. 2017;116:156.

    Article  CAS  PubMed  Google Scholar 

  74. Nigro ND, Vaitkevicius VK, Considine B. Combined therapy for cancer of the anal canal: a preliminary report. Dis Colon Rectum. 1974;17:354–6.

    Article  CAS  PubMed  Google Scholar 

  75. Gerard J, Chapet O, Samiei F, Morignat E, Isaac S, Paulin C, Romestaing P, Favrel V, Mornex F, Bobin J. Management of inguinal lymph node metastases in patients with carcinoma of the anal canal: experience in a series of 270 patients treated in Lyon and review of the literature. Cancer. 2001;92:77–84.

    Article  CAS  PubMed  Google Scholar 

  76. Ortholan C, Resbeut M, Hannoun-Levi J-M, Teissier E, Gerard J-P, Ronchin P, Zaccariotto A, Minsat M, Benezery K, François E. Anal canal cancer: management of inguinal nodes and benefit of prophylactic inguinal irradiation (CORS-03 Study). Int J Radiat Oncol Biol Phys. 2012;82:1988–95.

    Article  PubMed  Google Scholar 

  77. Mahmud A, Poon R, Jonker D. PET imaging in anal canal cancer. 2017. Toronto: Cancer Care Ontario. Program in evidence- based care recommendation report no.: PET-17, available on the CCO website https://www.cancercareontario.ca/sites/ccocancercare/files/guidelines/full/pebcpet-17f_0.pdf.

  78. Benson AB, Venook A, Al-Hawary M, et al. Anal Carcinoma, Version 2.2018. J Natl Compr Cancer Netw. 2018;16:852–71.

    Article  Google Scholar 

  79. Party UACTW. Epidermoid anal cancer: results from the UKCCCR randomised trial of radiotherapy alone versus radiotherapy, 5-fluorouracil, and mitomycin. Lancet. 1996;348:1049–54.

    Article  Google Scholar 

  80. Ajani JA, Winter KA, Gunderson LL, Pedersen J, Benson AB, Thomas CR, Mayer RJ, Haddock MG, Rich TA, Willett C. Fluorouracil, mitomycin, and radiotherapy vs fluorouracil, cisplatin, and radiotherapy for carcinoma of the anal canal: a randomized controlled trial. JAMA. 2008;299:1914–21.

    Article  CAS  PubMed  Google Scholar 

  81. Bartelink H, Roelofsen F, Eschwege F, Rougier P, Bosset JF, Gonzalez DG, Peiffert D, Van Glabbeke M, Pierart M. 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 Gastro. J Clin Oncol. 1997;15:2040–9.

    Article  CAS  PubMed  Google Scholar 

  82. Flam M, John M, Pajak TF, Petrelli N, Myerson R, Doggett S, Quivey J, Rotman M, Kerman H, Coia L. 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;14:2527–39.

    Article  CAS  PubMed  Google Scholar 

  83. Spithoff K, Cummings B, Jonker D, Biagi J, Gastrointestinal Cancer Disease Site Group. Management of squamous cell cancer of the anal canal. Toronto: Cancer Care Ontario. Program in Evidence-based Care Evidence-Based Series No.: 2–8 Version 2 2013.

    Google Scholar 

  84. Gunderson LL, Winter KA, Ajani JA, Pedersen JE, Moughan J, Benson AB III, Thomas CR Jr, Mayer RJ, Haddock MG, Rich TA. Long-term update of US GI intergroup RTOG 98-11 phase III trial for anal carcinoma: survival, relapse, and colostomy failure with concurrent chemoradiation involving fluorouracil/mitomycin versus fluorouracil/cisplatin. J Clin Oncol. 2012;30:4344.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. James RD, Glynne-Jones R, Meadows HM, Cunningham D, Myint AS, Saunders MP, Maughan T, McDonald A, Essapen S, Leslie M. Mitomycin or cisplatin chemoradiation with or without maintenance chemotherapy for treatment of squamous-cell carcinoma of the anus (ACT II): a randomised, phase 3, open-label, 2× 2 factorial trial. Lancet Oncol. 2013;14:516–24.

    Article  CAS  PubMed  Google Scholar 

  86. Peiffert D, Tournier-Rangeard L, Gérard J-P, Lemanski C, François E, Giovannini M, Cvitkovic F, Mirabel X, Bouché O, Luporsi E. Induction chemotherapy and dose intensification of the radiation boost in locally advanced anal canal carcinoma: final analysis of the randomized UNICANCER ACCORD 03 trial. J Clin Oncol. 2012;30:1941–8.

    Article  CAS  PubMed  Google Scholar 

  87. Tan KK, Pal S, Lee PJ, Rodwell L, Solomon MJ. Pelvic exenteration for recurrent squamous cell carcinoma of the pelvic organs arising from the cloaca–a single institution’s experience over 16 years. Color Dis. 2013;15:1227–31.

    Article  CAS  Google Scholar 

  88. Schiller DE, Cummings BJ, Rai S, Le LW, Last L, Davey P, Easson A, Smith AJ, Swallow CJ. Outcomes of salvage surgery for squamous cell carcinoma of the anal canal. Ann Surg Oncol. 2007;14:2780–9.

    Article  PubMed  Google Scholar 

  89. Harris DA, Williamson J, Davies M, Evans MD, Drew P, Beynon J, Group SPO. Outcome of salvage surgery for anal squamous cell carcinoma. Color Dis. 2013;15:968–73.

    Article  CAS  Google Scholar 

  90. Nilsson PJ, Svensson C, Goldman S, Glimelius B. Salvage abdominoperineal resection in anal epidermoid cancer. Br J Surg. 2002;89:1425–9.

    Article  CAS  PubMed  Google Scholar 

  91. Sunesen KG, Buntzen S, Tei T, Lindegaard JC, Nørgaard M, Laurberg S. Perineal healing and survival after anal cancer salvage surgery: 10-year experience with primary perineal reconstruction using the vertical rectus abdominis myocutaneous (VRAM) flap. Ann Surg Oncol. 2009;16:68–77.

    Article  CAS  PubMed  Google Scholar 

  92. Hallemeier CL, You YN, Larson DW, Dozois EJ, Nelson H, Klein KA, Miller RC, Haddock MG. Multimodality therapy including salvage surgical resection and intraoperative radiotherapy for patients with squamous-cell carcinoma of the anus with residual or recurrent disease after primary chemoradiotherapy. Dis Colon Rectum. 2014;57:442–8.

    Article  PubMed  Google Scholar 

  93. Hannes S, Reinisch A, Bechstein WO, Habbe N. Salvage abdominoperineal excisions in recurrent anal cancer—impact of different reconstruction techniques on outcome, morbidity, and complication rates. Int J Color Dis. 2016;31:653–9.

    Article  Google Scholar 

  94. Bignell M, Chave H, Branagan G. Outcome of surgery for recurrent anal cancer–results from a tertiary referral centre. Colorectal Dis. 2018;20(9):771–7.

    Google Scholar 

  95. Akbari RP, Paty PB, Guillem JG, Weiser MR, Temple LK, Minsky BD, Saltz L, Wong WD. Oncologic outcomes of salvage surgery for epidermoid carcinoma of the anus initially managed with combined modality therapy. Dis Colon Rectum. 2004;47:1136–44.

    Article  PubMed  Google Scholar 

  96. Eeson G, Foo M, Harrow S, McGregor G, Hay J. Outcomes of salvage surgery for epidermoid carcinoma of the anus following failed combined modality treatment. Am J Surg. 2011;201:628–33.

    Article  PubMed  Google Scholar 

  97. Blinde SE, Schasfoort R, Mens JW, Verhoef C, Olofsen M, Nuyttens JJ. Inguinal lymph node recurrence in the untreated groin of patients with anal carcinoma. Dis Colon Rectum. 2014;57:578–84.

    Article  PubMed  Google Scholar 

  98. Glynne-Jones R, Sebag-Montefiore D, Meadows HM, Cunningham D, Begum R, Adab F, Benstead K, Harte RJ, Stewart J, Beare S. Best time to assess complete clinical response after chemoradiotherapy in squamous cell carcinoma of the anus (ACT II): a post-hoc analysis of randomised controlled phase 3 trial. Lancet Oncol. 2017;18:347–56.

    Article  PubMed  PubMed Central  Google Scholar 

  99. Chai CY, Cao HT, Awad S, Massarweh NN. Management of stage I squamous cell carcinoma of the anal canal. JAMA Surg. 2018;153:209–15.

    Article  PubMed  Google Scholar 

  100. Renehan AG, Saunders MP, Schofield PF, O’Dwyer ST. Patterns of local disease failure and outcome after salvage surgery in patients with anal cancer. Br J Surg Inc Eur J Surg Swiss Surg. 2005;92:605–14.

    CAS  Google Scholar 

  101. Cummings BJ. Metastatic anal cancer: the search for cure. Oncol Res Treat. 2006;29:5–6.

    Article  Google Scholar 

  102. Northover J, Glynne-Jones R, Sebag-Montefiore D, James R, Meadows H, Wan S, Jitlal M, Ledermann J. Chemoradiation for the treatment of epidermoid anal cancer: 13-year follow-up of the first randomised UKCCCR Anal Cancer Trial (ACT I). Br J Cancer. 2010;102:1123.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Kim S, François E, André T, Samalin E, Jary M, El Hajbi F, Baba-Hamed N, Pernot S, Kaminsky M-C, Bouché O. Docetaxel, cisplatin, and fluorouracil chemotherapy for metastatic or unresectable locally recurrent anal squamous cell carcinoma (Epitopes-HPV02): a multicentre, single-arm, phase 2 study. Lancet Oncol. 2018;19:1094–106.

    Article  CAS  PubMed  Google Scholar 

  104. Morris VK, Salem ME, Nimeiri H, Iqbal S, Singh P, Ciombor K, Polite B, Deming D, Chan E, Wade JL. Nivolumab for previously treated unresectable metastatic anal cancer (NCI9673): a multicentre, single-arm, phase 2 study. Lancet Oncol. 2017;18:446–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Ott PA, Piha-Paul SA, Munster P, Pishvaian MJ, Van Brummelen EMJ, Cohen RB, Gomez-Roca C, Ejadi S, Stein M, Chan E. Safety and antitumor activity of the anti-PD-1 antibody pembrolizumab in patients with recurrent carcinoma of the anal canal. Ann Oncol. 2017;28:1036–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Pawlik TM, Gleisner AL, Bauer TW, Adams RB, Reddy SK, Clary BM, Martin RC, Scoggins CR, Tanabe KK, Michaelson JS. Liver-directed surgery for metastatic squamous cell carcinoma to the liver: results of a multi-center analysis. Ann Surg Oncol. 2007;14:2807–16.

    Article  PubMed  Google Scholar 

  107. Cummings BJ, Harwood AR, Keane TJ, Thomas GM, Rider WD. Combined treatment of squamous cell carcinoma of the anal canal: radical radiation therapy with 5-fluorouracil and mitomycin-C, a preliminary report. Dis Colon Rectum. 1980;23:389–91.

    Article  CAS  PubMed  Google Scholar 

  108. Kachnic LA, Winter K, Myerson RJ, Goodyear MD, Willins J, Esthappan J, Haddock MG, Rotman M, Parikh PJ, Safran H. RTOG 0529: a phase 2 evaluation of dose-painted intensity modulated radiation therapy in combination with 5-fluorouracil and mitomycin-C for the reduction of acute morbidity in carcinoma of the anal canal. Int J Radiat Oncol Biol Phys. 2013;86:27–33.

    Article  CAS  PubMed  Google Scholar 

  109. Hosni A, Han K, Le LW, Ringash J, Brierley J, Wong R, Dinniwell R, Brade A, Dawson LA, Cummings BJ. The ongoing challenge of large anal cancers: prospective long term outcomes of intensity-modulated radiation therapy with concurrent chemotherapy. Oncotarget. 2018;9:20439.

    Article  PubMed  PubMed Central  Google Scholar 

  110. Correa JHS, Castro LS, Kesley R, Dias JA, Jesus JP, Olivatto LO, Martins IO, Lopasso FP. Salvage abdominoperineal resection for anal cancer following chemoradiation: a proposed scoring system for predicting postoperative survival. J Surg Oncol. 2013;107:486–92.

    Article  PubMed  Google Scholar 

  111. Lefèvre JH, Corte H, Tiret E, Boccara D, Chaouat M, Touboul E, Svrcek M, Lefrancois M, Shields C, Parc Y. Abdominoperineal resection for squamous cell anal carcinoma: survival and risk factors for recurrence. Ann Surg Oncol. 2012;19:4186–92.

    Article  PubMed  Google Scholar 

  112. Glynne-Jones R, Meadows HM, Lopes A, Adams RA, Samuel LM, Hill J, Renehan A, Hawkins MA, Sebag-Montefiore D, Study ACTII. Salvage surgery with abdominoperineal excision of the rectum (APER) following loco-regional failure after chemoradiation (CRT) using mitomycin (MMC) or cisplatin (CisP), with or without maintenance 5FU/CisP chemotherapy (CT) in squamous cell carcinoma of the anus (SCCA) and the impact on long-term outcomes: results of ACT II. 2016.

    Google Scholar 

  113. Pedersen TB, Gocht-Jensen P, Klein MF. 30-day and long-term outcome following salvage surgery for squamous cell carcinoma of the anus. Eur J Surg Oncol. 2018;44:1518–21.

    Article  CAS  PubMed  Google Scholar 

  114. Petrosky E, Bocchini JJA, Hariri S, Chesson H, Curtis CR, Saraiya M, Unger ER, Markowitz LE. Use of 9-valent human papillomavirus (HPV) vaccine: updated HPV vaccination recommendations of the advisory committee on immunization practices. MMWR Morb Mortal Wkly Rep. 2015;64:300–4.

    PubMed  PubMed Central  Google Scholar 

  115. National Advisory Committee on Immunization. Update on the recommended human papillomavirus (HPV) vaccine immunization schedule. Public Heal. Agency Canada. 2015.

    Google Scholar 

  116. Patel C, Brotherton JML, Pillsbury A, Jayasinghe S, Donovan B, Macartney K, Marshall H. The impact of 10 years of human papillomavirus (HPV) vaccination in Australia: what additional disease burden will a nonavalent vaccine prevent? Eurosurveillance. 2018;23(41):1700737.

    Article  PubMed Central  Google Scholar 

  117. Palefsky JM, Giuliano AR, Goldstone S, Moreira ED Jr, Aranda C, Jessen H, Hillman R, Ferris D, Coutlee F, Stoler MH. HPV vaccine against anal HPV infection and anal intraepithelial neoplasia. N Engl J Med. 2011;365:1576–85.

    Article  CAS  PubMed  Google Scholar 

  118. Arbyn M, Xu L. Efficacy and safety of prophylactic HPV vaccines. A Cochrane review of randomized trials. Expert Rev Vaccines. 2018;17(12):1–7.

    Google Scholar 

  119. Signorelli C, Odone A, Ciorba V, Cella P, Audisio RA, Lombardi A, Mariani L, Mennini FS, Pecorelli S, Rezza G. Human papillomavirus 9-valent vaccine for cancer prevention: a systematic review of the available evidence. Epidemiol Infect. 2017;145:1962–82.

    Article  CAS  PubMed  Google Scholar 

  120. Palefsky JM. Screening to prevent anal cancer: current thinking and future directions. Cancer Cytopathol. 2015;123:509–10.

    Article  PubMed  Google Scholar 

  121. Leeds IL, Fang SH. Anal cancer and intraepithelial neoplasia screening: a review. World J Gastrointest Surg. 2016;8:41.

    Article  PubMed  PubMed Central  Google Scholar 

  122. Clarke MA, Wentzensen N. Strategies for screening and early detection of anal cancers: a narrative and systematic review and meta-analysis of cytology, HPV testing, and other biomarkers. Cancer Cytopathol. 2018;126(7):447–60.

    Article  PubMed  PubMed Central  Google Scholar 

  123. Machalek DA, Grulich AE, Hillman RJ, Jin F, Templeton DJ, Tabrizi SN, Garland SM, Prestage G, McCaffery K, Howard K. The Study of the Prevention of Anal Cancer (SPANC): design and methods of a three-year prospective cohort study. BMC Public Health. 2013;13:946.

    Article  PubMed  PubMed Central  Google Scholar 

  124. Berry JM, Jay N, Cranston RD, Darragh TM, Holly EA, Welton ML, Palefsky JM. Progression of anal high-grade squamous intraepithelial lesions to invasive anal cancer among HIV-infected men who have sex with men. Int J Cancer. 2014;134:1147–55.

    Article  CAS  PubMed  Google Scholar 

  125. Sambursky JA, Terlizzi JP, Goldstone SE. Testing for human papillomavirus strains 16 and 18 helps predict the presence of anal high-grade squamous intraepithelial lesions. Dis Colon Rectum. 2018;61:1364–71.

    Article  PubMed  Google Scholar 

  126. Schofield AM, Sadler L, Nelson L, Gittins M, Desai M, Sargent A, McMahon RFT, Hill J, Crosbie EJ, Patnick J. A prospective study of anal cancer screening in HIV-positive and negative MSM. AIDS. 2016;30:1375–83.

    Article  PubMed  Google Scholar 

  127. Nayar R, Wilbur DC The Bethesda system for reporting cervical cytology: definitions, criteria, and explanatory notes. Switzerland: Springer; 2015.

    Google Scholar 

  128. Jin F, Grulich AE, Poynten IM, Hillman RJ, Templeton DJ, Law CLH, Farnsworth A, Garland SM, Fairley CK, Roberts JM. The performance of anal cytology as a screening test for anal HSILs in homosexual men. Cancer Cytopathol. 2016;124:415–24.

    Article  PubMed  Google Scholar 

  129. Templeton DJ, Roberts JM, Poynten IM, Law C, Hillman RJ, Farnsworth A, Fairley CK, Tabrizi SN, Garland SM, Grulich AE. Prevalence and predictors of unsatisfactory anal cytology tests in a cohort of gay and bisexual men in Sydney, Australia: baseline findings from the Study of the Prevention of Anal Cancer (SPANC). Eur J Cancer Prev. 2017;26:212–6.

    Article  PubMed  Google Scholar 

  130. Darragh TM, Tokugawa D, Castle PE, Follansbee S, Borgonovo S, LaMere BJ, Schwartz L, Gage JC, Fetterman B, Lorey T. Interrater agreement of anal cytology. Cancer Cytopathol. 2013;121:72–8.

    Article  PubMed  Google Scholar 

  131. Darragh TM, Winkler B, Souers RJ, Laucirica R, Zhao C, Moriarty AT. Room for improvement: initial experience with anal cytology: observations from the College of American Pathologists interlaboratory comparison program in nongynecologic cytology. Arch Pathol Lab Med. 2013;137:1550–4.

    Article  PubMed  Google Scholar 

  132. Han K, Cummings BJ, Lindsay P, Skliarenko J, Craig T, Le LW, Brierley J, Wong R, Dinniwell R, Bayley AJ. Prospective evaluation of acute toxicity and quality of life after IMRT and concurrent chemotherapy for anal canal and perianal cancer. Int J Radiat Oncol Biol Phys. 2014;90:587–94.

    Article  PubMed  Google Scholar 

  133. Glynne-Jones R, Tan D, Hughes R, Hoskin P. Squamous-cell carcinoma of the anus: progress in radiotherapy treatment. Nat Rev Clin Oncol. 2016;13:447.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. General Surgical Oncology, University of Toronto, Toronto, ON, Canada

    Tyler R. Chesney

  2. Department of Medicine, University of Toronto, Toronto, ON, Canada

    Edward Weiss & Monika K. Krzyzanowska

  3. Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada

    Ali Hosni & James Brierley

  4. Department of Surgery, University of Toronto, Toronto, ON, Canada

    Alexandra M. Easson

Authors
  1. Tyler R. Chesney
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Edward Weiss
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Monika K. Krzyzanowska
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ali Hosni
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. James Brierley
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Alexandra M. Easson
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Surgery, University of Toronto, Toronto, ON, Canada

    Frances C. Wright

  2. Department of Surgery, University of Toronto, Toronto, ON, Canada

    Jaime M. Escallon

  3. Department of Surgery, University of Toronto, Toronto, ON, Canada

    Moises Cukier

  4. Department of Surgery, University of Toronto, Toronto, ON, Canada

    Melanie E. Tsang

  5. Department of Surgery, University of Toronto, Toronto, ON, Canada

    Usmaan Hameed

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Chesney, T.R., Weiss, E., Krzyzanowska, M.K., Hosni, A., Brierley, J., Easson, A.M. (2020). Anal Cancer. In: Wright, F., Escallon, J., Cukier, M., Tsang, M., Hameed, U. (eds) Surgical Oncology Manual. Springer, Cham. https://doi.org/10.1007/978-3-030-48363-0_3

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-48363-0_3

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-48362-3

  • Online ISBN: 978-3-030-48363-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation