Register      Login
Sexual Health Sexual Health Society
Publishing on sexual health from the widest perspective
Shopping Cart: ( empty )
You are here: Home > Journals > SH > SH12010
REVIEW
Contents Vol 9(6)

Squamous cell carcinoma of the anal canal: a review of the aetiology, presentation, staging, prognosis and methods available for treatment

Ursula M. Szmulowicz A B and James S. Wu A
+ Author Affiliations
- Author Affiliations

A Department of Colon and Rectal Surgery, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.

B Corresponding author. Email: szmulou@ccf.org

Sexual Health 9(6) 593-609 https://doi.org/10.1071/SH12010
Submitted: 20 January 2012  Accepted: 8 March 2012   Published: 31 August 2012

Abstract

Anal cancer is an uncommon malignancy, with the majority of cases comprised of squamous cell carcinomas. The increasing incidence of this disease reflects a rise in the transmission of the human papillomavirus, the causative organism of most tumours. Abdominoperineal resection (APR), once the primary mode of treatment, has been supplanted by sphincter-saving combination chemoradiation as the first-line therapy. However, surgeons continue to play a role in the multidisciplinary management of patients with anal cancer for diagnosis and post-treatment surveillance. Sentinel node biopsy may identify patients with clinically and radiographically negative inguinal lymph nodes who will benefit from groin irradiation. In very select cases, the controversial means of local excision has been employed as primary treatment, often in conjunction with radiation and chemotherapy. The management of persistent or recurrent anal cancers following primary chemoradiation remains a concern, for which only salvage APR currently offers the possibility of a cure. The introduction of human papillomavirus vaccines presents the exciting potential for the eradication of the disease.

Additional keywords: abdominoperineal resection, chemotherapy, dissection, human papillomavirus, lymph nodes, radiation.


References

[1]  Siegel R, Ward E, Brawley O, Jemal A. Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin 2011; 61 212–36.
| Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths.Crossref | GoogleScholarGoogle Scholar |

[2]  Nigro ND. An evaluation of combined therapy for squamous cell cancer of the anal canal. Dis Colon Rectum 1984; 27 763–6.
| An evaluation of combined therapy for squamous cell cancer of the anal canal.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaL2M%2FltVKluw%3D%3D&md5=98f8cd053694bbe0cdaa25abec9d929eCAS |

[3]  Williams GR, Talbot IC. Anal carcinoma – a histological review. Histopathology 1994; 25 507–16.
| Anal carcinoma – a histological review.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK2M3ht12qtg%3D%3D&md5=579c56914fe5f4d22f810e2e9b427c45CAS |

[4]  Dougherty BG, Evans HL. Carcinoma of the anal canal: a study of 79 cases. Am J Clin Pathol 1985; 83 159–64.
| 1:STN:280:DyaL2M7hvFWntw%3D%3D&md5=c533072a9fea3d363335e7dfbd417adeCAS |

[5]  Singh R, Nime F, Mittelman A. Malignant epithelial tumors of the anal canal. Cancer 1981; 48 411–5.
| Malignant epithelial tumors of the anal canal.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaL3M3gvFyktg%3D%3D&md5=728f3bd9e88d5001fd991b438ad1df47CAS |

[6]  Shia J. An update on tumors of the anal canal. Arch Pathol Lab Med 2010; 134 1601–11.

[7]  Surveillance Epidemiology and End Results (SEER). SEER stat fact sheets: anal cancer. Bethesda: SEER; 2011. Available online at: http://seer.cancer.gov/statfacts/html/anus.html [verified September 2011].

[8]  Pokorny WJ, Rothenberg SS, Brandt ML. Growth and development. In O’Leary JP, Capote LR, editors. The physiologic basis of surgery, 2nd ed. Philadelphia: Lippincott, Williams, & Wilkins; 1996. p. 61–66.

[9]  Moore K, Persaud T. The developing human: clinically oriented embryology, 8th ed. Philadelphia: Saunders; 2007.

[10]  Penington EC, Hutson JM. The cloacal plate: the missing link in anorectal and urogenital development. BJU Int 2002; 89 726–32.
| The cloacal plate: the missing link in anorectal and urogenital development.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD383ivFChsg%3D%3D&md5=eaf0d8b0131513a90e6e72c602bf1d03CAS |

[11]  Zhang T, Zhang HL, Wang J, Tang XB, Jia HM, Bai YZ, et al Normal development of hindgut and anorectum in human embryo. Int J Colorectal Dis 2011; 26 109–16.
| Normal development of hindgut and anorectum in human embryo.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XisFCiur0%3D&md5=86f0ce58edc04a70bf60955541299df0CAS |

[12]  Godlewski G, Prudhomme M. Embryology and anatomy of the anorectum. Basis of surgery. Surg Clin North Am 2000; 80 319–43.
| Embryology and anatomy of the anorectum. Basis of surgery.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD3c7kvFCitA%3D%3D&md5=a5f4cd93e20b20e7c4c9d7968d8db4f1CAS |

[13]  Akita K, Yamaguchi K, Sasaki C, Sato T. An embryological study of the anorectal system in mice. J Anat 2002; 201 417–34.

[14]  Chawla AK, Willett CG. Squamous cell carcinoma of the anal canal and anal margin. Hematol Oncol Clin North Am 2001; 15 321–344.
| Squamous cell carcinoma of the anal canal and anal margin.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD38%2FhtVamsA%3D%3D&md5=bbb15de24995e477c607960610d4049eCAS |

[15]  Oliver GC, Labow SB. Neoplasms of the anus. Surg Clin North Am 1994; 74 1475–90.
| 1:STN:280:DyaK2M%2Fns1emsA%3D%3D&md5=1a63bb3a0a190a8cbdd48d90185bab78CAS |

[16]  Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A, editors. AJCC cancer staging manual, 7th ed. New York: Springer; 2010.

[17]  Klotz RG, Pamukcoglu T, Souilliard DH. Transitional cloacogenic carcinoma of the anal canal. Clinicopathologic study of three hundred seventy-three cases. Cancer 1967; 20 1727–45.
| Transitional cloacogenic carcinoma of the anal canal. Clinicopathologic study of three hundred seventy-three cases.Crossref | GoogleScholarGoogle Scholar |

[18]  Stearns MW, Urmacher C, Sternberg SS, Woodruff J, Attiyeh F. Cancer of the anal canal. Curr Probl Cancer 1980; 4 1–44.
| Cancer of the anal canal.Crossref | GoogleScholarGoogle Scholar |

[19]  Balamucki CJ, Zlotecki RA, Rout WR, Newlin HE, Morris CG, Kirwan JM, et al Squamous cell carcinoma of the anal margin: the University of Florida experience. Am J Clin Oncol 2011; 34 406–10.
| Squamous cell carcinoma of the anal margin: the University of Florida experience.Crossref | GoogleScholarGoogle Scholar |

[20]  Greenall MJ, Quan SH, DeCosse JJ. Epidermoid cancer of the anus. Br J Surg 1985; 72 S97–103.
| Epidermoid cancer of the anus.Crossref | GoogleScholarGoogle Scholar |

[21]  Skibber J, Rodriguez-Bigas MA, Gordon PH. Surgical considerations in anal cancer. Surg Oncol Clin N Am 2004; 13 321–38.
| Surgical considerations in anal cancer.Crossref | GoogleScholarGoogle Scholar |

[22]  Everett T, Bryant A, Griffin MF, Martin-Hirsch PP, Forbes CA, Jepson RG. Interventions targeted at women to encourage the uptake of cervical screening. Cochrane Database Syst Rev 2011; 002 834

[23]  Cohen AM, Wong WD. Anal squamous cell cancer nodal metastases: prognostic significance and therapeutic considerations. Surg Oncol Clin N Am 1996; 5 203–10.
| 1:STN:280:DyaK28zotFCqsg%3D%3D&md5=8d4d07e1fa59386198cd654b7da30f47CAS |

[24]  De Nardi P, Carvello M, Canevari C, Passoni P, Staudacher C. Sentinel node biopsy in squamous-cell carcinoma of the anal canal. Ann Surg Oncol 2011; 18 365–70.
| Sentinel node biopsy in squamous-cell carcinoma of the anal canal.Crossref | GoogleScholarGoogle Scholar |

[25]  Buxton RW. Squamous cell anal carcinoma. AMA Arch Surg 1953; 67 821–38.
| Squamous cell anal carcinoma.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaG2c%2FisVymsg%3D%3D&md5=be642cc9ad6cb3a5b87c1909a72f8d99CAS |

[26]  Clark J, Petrelli N, Herrera L, Mittelman A. Epidermoid carcinoma of the anal canal. Cancer 1986; 57 400–6.
| Epidermoid carcinoma of the anal canal.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaL287gsFKhsQ%3D%3D&md5=fafc520a5856de8e300e29df9c5f9014CAS |

[27]  Kuehn PG, Eisenberg H, Reed JF. Epidermoid carcinoma of the perianal skin and anal canal. Cancer 1968; 22 932–8.
| Epidermoid carcinoma of the perianal skin and anal canal.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaF1M%2Fis12qsg%3D%3D&md5=96746c8801e3ad41b59856b5f7794f9aCAS |

[28]  Palmer JG, Scholefield JH, Coates PJ, Shepherd NA, Jass JR, Crawford LV, et al Anal cancer and human papillomaviruses. Dis Colon Rectum 1989; 32 1016–22.
| Anal cancer and human papillomaviruses.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK3c%2FnsF2jsQ%3D%3D&md5=20ca8fa2df1314b93890d4dcb24e25c3CAS |

[29]  Williams GR, Lu QL, Love SB, Talbot IC, Northover JM. Properties of HPV-positive and HPV-negative anal carcinomas. J Pathol 1996; 180 378–82.
| Properties of HPV-positive and HPV-negative anal carcinomas.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK2s7mslWlug%3D%3D&md5=2b60997c349a62a4b4b38e797655537bCAS |

[30]  Frisch M, Glimelius B, van den Brule AJ, Wohlfahrt J, Meijer CJ, Walboomers JM, et al Sexually transmitted infection as a cause of anal cancer. N Engl J Med 1997; 337 1350–8.
| Sexually transmitted infection as a cause of anal cancer.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK1c%2FgtVSjtg%3D%3D&md5=85b48368c0091b3841291d9bd7f8096cCAS |

[31]  Chaturvedi AK. Beyond cervical cancer: burden of other HPV-related cancers among men and women. J Adolesc Health 2010; 46 S20–6.
| Beyond cervical cancer: burden of other HPV-related cancers among men and women.Crossref | GoogleScholarGoogle Scholar |

[32]  Oriel JD, Whimster IW. Carcinoma in situ associated with virus-containing anal warts. Br J Dermatol 1971; 84 71–3.
| Carcinoma in situ associated with virus-containing anal warts.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaE3M7otF2gsw%3D%3D&md5=5ece08df14341a5371b2abc60abae040CAS |

[33]  Parkin DM, Bray F. Chapter 2: the burden of HPV-related cancers. Vaccine 2006; 24 S11–25.
| Chapter 2: the burden of HPV-related cancers.Crossref | GoogleScholarGoogle Scholar |

[34]  Stanley M. Prophylactic HPV vaccines: prospects for eliminating ano-genital cancer. Br J Cancer 2007; 96 1320–3.
| 1:STN:280:DC%2BD2s3mt1GhsA%3D%3D&md5=4e006e45c96f5b11d47ce67f09269791CAS |

[35]  Muñoz N, Castellsague X, de Gonzalez AB, Gissmann L. Chapter 1: HPV in the etiology of human cancer. Vaccine 2006; 24 S1–10.
| Chapter 1: HPV in the etiology of human cancer.Crossref | GoogleScholarGoogle Scholar |

[36]  Palefsky JM. Anal squamous intraepithelial lesions: relation to HIV and human papillomavirus infection. J Acquir Immune Defic Syndr 1999; 21 S42–8.

[37]  Lorenz HP, Wilson W, Leigh B, Crombleholme T, Schecter W. Squamous cell carcinoma of the anus and HIV infection. Dis Colon Rectum 1991; 34 336–8.
| Squamous cell carcinoma of the anus and HIV infection.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK3M7ns1yitg%3D%3D&md5=49fd41f869545216adbed326b1b82f96CAS |

[38]  Khatri VP, Chopra S. Clinical presentation, imaging, and staging of anal cancer. Surg Oncol Clin N Am 2004; 13 295–308.
| Clinical presentation, imaging, and staging of anal cancer.Crossref | GoogleScholarGoogle Scholar |

[39]  Fleshner PR, Chalasani S, Chang GJ, Levien DH, Hyman NH, Buie WD. (Standards Practice Task Force, American Society of Colon and Rectal Surgeons). Practice parameters for anal squamous neoplasms. Dis Colon Rectum 2008; 51 2–9.
| (Standards Practice Task Force, American Society of Colon and Rectal Surgeons). Practice parameters for anal squamous neoplasms.Crossref | GoogleScholarGoogle Scholar |

[40]  Buckwalter JA, Jurayj MN. Relationship of chronic anorectal disease to carcinoma. AMA Arch Surg 1957; 75 352–361.
| Relationship of chronic anorectal disease to carcinoma.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaG1c%2FgtVajsA%3D%3D&md5=1978ad8c493f61cc0ce8153ccce92a79CAS |

[41]  Kline RJ, Spencer RJ. Harrison EG. Carcinoma associated with fistula-in-ano. Arch Surg 1964; 89 989–94.
| Harrison EG. Carcinoma associated with fistula-in-ano.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaF2M%2Fht1yltg%3D%3D&md5=05c0a7bd8c799e06282b13c15e2f6ef6CAS |

[42]  Milliken JC. Squamous carcinoma arising in an anal fistula. Br J Surg 1960; 48 224
| Squamous carcinoma arising in an anal fistula.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaF3c%2FptV2rug%3D%3D&md5=d44ec596be55287bf8e1f54c0e318bc1CAS |

[43]  Stearns MW, Quan SH. Epidermoid carcinoma of the anorectum. Surg Gynecol Obstet 1970; 131 953–7.

[44]  Myerson RJ, Karnell LH, Menck HR. The National Cancer Data Base report on carcinoma of the anus. Cancer 1997; 80 805–15.
| The National Cancer Data Base report on carcinoma of the anus.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK2svgslKitA%3D%3D&md5=3383e1b35ffbbd9946886b47822fa401CAS |

[45]  Mistrangelo M, Pelosi E, Bello M, Castellano I, Cassoni P, Ricardi U, et al Comparison of positron emission tomography scanning and sentinel node biopsy in the detection of inguinal node metastases in patients with anal cancer. Int J Radiat Oncol Biol Phys 2010; 77 73–8.
| Comparison of positron emission tomography scanning and sentinel node biopsy in the detection of inguinal node metastases in patients with anal cancer.Crossref | GoogleScholarGoogle Scholar |

[46]  Abbas A, Yang G, Fakih M. Management of anal cancer in 2010. Part 1: overview, screening, and diagnosis. Oncology 2010; 24 364–9.

[47]  Nigro ND. Multidisciplinary management of cancer of the anus. World J Surg 1987; 11 446–51.
| Multidisciplinary management of cancer of the anus.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaL2szitFCgsA%3D%3D&md5=4193d3161d781ef8b695b174b62f14c3CAS |

[48]  Hardcastle JD, Bussey HJ. Results of surgical treatment of squamous cell carcinoma of the anal canal and anal margin seen at St. Mark’s Hospital 1928–66. Proc R Soc Med 1968; 61 629–30.
| 1:STN:280:DyaF1czis1Gntw%3D%3D&md5=35c437c4d88e52326e485c3edca16a90CAS |

[49]  Boman BM, Moertel CG, O’Connell MJ, Scott M, Weiland LH, Beart RW, et al Carcinoma of the anal canal. A clinical and pathologic study of 188 cases. Cancer 1984; 54 114–25.
| Carcinoma of the anal canal. A clinical and pathologic study of 188 cases.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaL2c3gsFanug%3D%3D&md5=4e189d1138a8067ce4e2f5d7dbb8ddbfCAS |

[50]  Frost DB, Richards PC, Montague ED, Giacco GG, Martin RG. Epidermoid cancer of the anorectum. Cancer 1984; 53 1285–93.
| Epidermoid cancer of the anorectum.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaL2c7gs1eksg%3D%3D&md5=57bb934a7f92209a5a3a9c7a4afa5c02CAS |

[51]  Greenall MJ, Quan SH, Urmacher C, DeCosse JJ. Treatment of epidermoid carcinoma of the anal canal. Surg Gynecol Obstet 1985; 161 509–17.
| 1:STN:280:DyaL28%2FntVyitQ%3D%3D&md5=7595dc3a912f3f257dd2c401fcbc747aCAS |

[52]  Nigro ND. The force of change in the management of squamous-cell cancer of the anal canal. Dis Colon Rectum 1991; 34 482–6.
| The force of change in the management of squamous-cell cancer of the anal canal.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK3M3ktlGlsg%3D%3D&md5=326341128416ed83129ec2fbc6e872b4CAS |

[53]  Nigro ND, Vaitkevicius VK, Considine B. Combined therapy for cancer of the anal canal: a preliminary report. Dis Colon Rectum 1974; 17 354–6.
| Combined therapy for cancer of the anal canal: a preliminary report.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaE2c7ntFelsA%3D%3D&md5=565c5723eb8ecf7401755f20c874e99bCAS |

[54]  Nigro ND. An evaluation of combined therapy for squamous cell cancer of the anal canal. Dis Colon Rectum 1984; 27 763–6.
| An evaluation of combined therapy for squamous cell cancer of the anal canal.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaL2M%2FltVKluw%3D%3D&md5=98f8cd053694bbe0cdaa25abec9d929eCAS |

[55]  UKCCCR Anal Cancer Trial Working Party. UK Co-ordinating Committee on Cancer Research. Epidermoid anal cancer: results from the UKCCCR randomised trial of radiotherapy alone versus radiotherapy, 5-fluorouracil, and mitomycin Lancet 1996; 348 1049–54.
| Epidermoid anal cancer: results from the UKCCCR randomised trial of radiotherapy alone versus radiotherapy, 5-fluorouracil, and mitomycinCrossref | GoogleScholarGoogle Scholar |

[56]  Bartelink H, Roelofsen F, Eschwege F, Rougier P, Bosset JF, Gonzalez DG, 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 2040–9.
| 1:CAS:528:DyaK2sXjsVCrt7k%3D&md5=92418c519fdbf7599ce72ec1bdbc23cbCAS |

[57]  Flam M, John M, Pajak TF, Petrelli N, Myerson R, Doggett S, 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 2527–39.
| 1:CAS:528:DyaK28XlvVGisr0%3D&md5=04243a7a59653c1c996895111d920988CAS |

[58]  Fraunholz I, Rabeneck D, Weiss C, Rodel C. Combined-modality treatment for anal cancer: current strategies and future directions. Strahlenther Onkol 2010; 186 361–6.
| Combined-modality treatment for anal cancer: current strategies and future directions.Crossref | GoogleScholarGoogle Scholar |

[59]  Chiao EY, Giordano TP, Richardson P, El-Serag HB. Human immunodeficiency virus-associated squamous cell cancer of the anus: epidemiology and outcomes in the highly active antiretroviral therapy era. J Clin Oncol 2008; 26 474–9.
| Human immunodeficiency virus-associated squamous cell cancer of the anus: epidemiology and outcomes in the highly active antiretroviral therapy era.Crossref | GoogleScholarGoogle Scholar |

[60]  Meyer J, Willett C, Czito B. Current and emerging treatment strategies for anal cancer. Curr Oncol Rep 2010; 12 168–74.
| Current and emerging treatment strategies for anal cancer.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXht1CjsbzI&md5=136b53baff402dee68c19fd9ac92b390CAS |

[61]  Zagar TM, Willett CG, Czito BG. Intensity-modulated radiation therapy for anal cancer: toxicity versus outcomes. Oncology 2010; 24 815–823.

[62]  Czito BG, Pepek JM, Meyer JJ, Yoo S, Willett CG. Intensity-modulated radiation therapy for anal cancer. Oncology 2009; 23 1082–9.

[63]  Saarilahti K, Arponen P, Vaalavirta L, Tenhunen M. The effect of intensity-modulated radiotherapy and high dose rate brachytherapy on acute and late radiotherapy-related adverse events following chemoradiotherapy of anal cancer. Radiother Oncol 2008; 87 383–90.
| The effect of intensity-modulated radiotherapy and high dose rate brachytherapy on acute and late radiotherapy-related adverse events following chemoradiotherapy of anal cancer.Crossref | GoogleScholarGoogle Scholar |

[64]  Pepek JM, Willett CG, Wu QJ, Yoo S, Clough RW, Czito BG. Intensity-modulated radiation therapy for anal malignancies: a preliminary toxicity and disease outcomes analysis. Int J Radiat Oncol Biol Phys 2010; 78 1413–9.
| Intensity-modulated radiation therapy for anal malignancies: a preliminary toxicity and disease outcomes analysis.Crossref | GoogleScholarGoogle Scholar |

[65]  Roohipour R, Patil S, Goodman KA, Minsky BD, Wong WD, Guillem JG, et al Squamous-cell carcinoma of the anal canal: predictors of treatment outcome. Dis Colon Rectum 2008; 51 147–53.
| Squamous-cell carcinoma of the anal canal: predictors of treatment outcome.Crossref | GoogleScholarGoogle Scholar |

[66]  Nilsson PJ, Svensson C, Goldman S, Glimelius B. Salvage abdominoperineal resection in anal epidermoid cancer. Br J Surg 2002; 89 1425–9.
| Salvage abdominoperineal resection in anal epidermoid cancer.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD38nmvFOrtA%3D%3D&md5=42826fdbdb9c06b8b97976fce53a9c31CAS |

[67]  Schraut WH, Wang CH, Dawson PJ, Block GE. Depth of invasion, location, and size of cancer of the anus dictate operative treatment. Cancer 1983; 51 1291–6.
| Depth of invasion, location, and size of cancer of the anus dictate operative treatment.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaL3s7ivVyrsw%3D%3D&md5=7417a7304368385a856b4b4f3142d725CAS |

[68]  Hu K, Minsky BD, Cohen AM, Kelsen DP, Guillem JG, Paty PP, et al 30 Gy may be an adequate dose in patients with anal cancer treated with excisional biopsy followed by combined-modality therapy. J Surg Oncol 1999; 70 71–7.
| 30 Gy may be an adequate dose in patients with anal cancer treated with excisional biopsy followed by combined-modality therapy.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK1M7ot1Wgug%3D%3D&md5=68d2d60d844fc895631456c49d3b6cf9CAS |

[69]  Ortholan C, Ramaioli A, Peiffert D, Lusinchi A, Romestaing P, Chauveinc L, et al Anal canal carcinoma: early-stage tumors < or = 10 mm (T1 or Tis): therapeutic options and original pattern of local failure after radiotherapy. Int J Radiat Oncol Biol Phys 2005; 62 479–85.
| Anal canal carcinoma: early-stage tumors < or = 10 mm (T1 or Tis): therapeutic options and original pattern of local failure after radiotherapy.Crossref | GoogleScholarGoogle Scholar |

[70]  Chorost MI, Weber TK, Lee RJ, Rodriguez-Bigas MA, Petrelli NJ. Sexual dysfunction, informed consent and multimodality therapy for rectal cancer. Am J Surg 2000; 179 271–4.
| Sexual dysfunction, informed consent and multimodality therapy for rectal cancer.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD3czjs1eqtw%3D%3D&md5=7883f126de346c748c0d6e05ee440b71CAS |

[71]  Eby LS, Sullivan ES. Current concepts of local excision of epidermoid carcinoma of the anus. Dis Colon Rectum 1969; 12 332–7.
| Current concepts of local excision of epidermoid carcinoma of the anus.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaE3c%2FgtFOqsg%3D%3D&md5=60941063c0114527f7a8e69e457ccfffCAS |

[72]  Lindkaer Jensen S, Hagen K, Harling H, Shokouh-Amiri MH, Nielsen OV. Long-term prognosis after radical treatment for squamous-cell carcinoma of the anal canal and anal margin. Dis Colon Rectum 1988; 31 273–8.
| Long-term prognosis after radical treatment for squamous-cell carcinoma of the anal canal and anal margin.Crossref | GoogleScholarGoogle Scholar |

[73]  Pintor MP, Northover JM, Nicholls RJ. Squamous cell carcinoma of the anus at one hospital from 1948 to 1984. Br J Surg 1989; 76 806–10.
| Squamous cell carcinoma of the anus at one hospital from 1948 to 1984.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaL1Mzltlektg%3D%3D&md5=2ce492cb1e0b37ee7258d9bd79559a3fCAS |

[74]  Hughes LL, Rich TA, Delclos L, Ajani JA, Martin RG. Radiotherapy for anal cancer: experience from 1979–1987. Int J Radiat Oncol Biol Phys 1989; 17 1153–60.
| Radiotherapy for anal cancer: experience from 1979–1987.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK3c%2Fptlyqtw%3D%3D&md5=1aeacc03679aae9d9eeae77d0f96180aCAS |

[75]  Longo WE, Vernava AM, Wade TP, Coplin MA, Virgo KS, Johnson FE. Recurrent squamous cell carcinoma of the anal canal. Predictors of initial treatment failure and results of salvage therapy. Ann Surg 1994; 220 40–9.
| Recurrent squamous cell carcinoma of the anal canal. Predictors of initial treatment failure and results of salvage therapy.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK2c3ps1Wksw%3D%3D&md5=4733f6fc2f1f9cb65597ad9f481d07d6CAS |

[76]  Martenson JA, Gunderson LL. External radiation therapy without chemotherapy in the management of anal cancer. Cancer 1993; 71 1736–40.
| External radiation therapy without chemotherapy in the management of anal cancer.Crossref | GoogleScholarGoogle Scholar |

[77]  Dobrowsky W. Radiotherapy of epidermoid anal canal cancer. Br J Radiol 1989; 62 53–8.
| Radiotherapy of epidermoid anal canal cancer.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaL1M7hvVyhtw%3D%3D&md5=368cd439f51c4a4ef1118b552569262aCAS |

[78]  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.
| Outcomes of salvage surgery for epidermoid carcinoma of the anus following failed combined modality treatment.Crossref | GoogleScholarGoogle Scholar |

[79]  Smith AJ, Whelan P, Cummings BJ, Stern HS. Management of persistent or locally recurrent epidermoid cancer of the anal canal with abdominoperineal resection. Acta Oncol 2001; 40 34–6.
| Management of persistent or locally recurrent epidermoid cancer of the anal canal with abdominoperineal resection.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD3M3jvVaktA%3D%3D&md5=ae3615df659e7aaa6795ed38f1932e78CAS |

[80]  Mullen JT, Rodriguez-Bigas MA, Chang GJ, Barcenas CH, Crane CH, Skibber JM, et al Results of surgical salvage after failed chemoradiation therapy for epidermoid carcinoma of the anal canal. Ann Surg Oncol 2007; 14 478–83.
| Results of surgical salvage after failed chemoradiation therapy for epidermoid carcinoma of the anal canal.Crossref | GoogleScholarGoogle Scholar |

[81]  Ellenhorn JD, Enker WE, Quan SH. Salvage abdominoperineal resection following combined chemotherapy and radiotherapy for epidermoid carcinoma of the anus. Ann Surg Oncol 1994; 1 105–10.
| Salvage abdominoperineal resection following combined chemotherapy and radiotherapy for epidermoid carcinoma of the anus.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK2M7js1Sgsg%3D%3D&md5=71beabd395570d849dbe9fcf70010a27CAS |

[82]  Schiller DE, Cummings BJ, Rai S, Le LW, Last L, Davey P, et al Outcomes of salvage surgery for squamous cell carcinoma of the anal canal. Ann Surg Oncol 2007; 14 2780–9.
| Outcomes of salvage surgery for squamous cell carcinoma of the anal canal.Crossref | GoogleScholarGoogle Scholar |

[83]  Akbari RP, Paty PB, Guillem JG, Weiser MR, Temple LK, Minsky BD, et al Oncologic outcomes of salvage surgery for epidermoid carcinoma of the anus initially managed with combined modality therapy. Dis Colon Rectum 2004; 47 1136–44.
| Oncologic outcomes of salvage surgery for epidermoid carcinoma of the anus initially managed with combined modality therapy.Crossref | GoogleScholarGoogle Scholar |

[84]  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 2005; 92 605–14.
| Patterns of local disease failure and outcome after salvage surgery in patients with anal cancer.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD2M3islyitg%3D%3D&md5=ad951c07b986ff8d84956526a887b365CAS |

[85]  Zelnick RS, Haas PA, Ajlouni M, Szilagyi E, Fox TA. Results of abdominoperineal resections for failures after combination chemotherapy and radiation therapy for anal canal cancers. Dis Colon Rectum 1992; 35 574–7.
| Results of abdominoperineal resections for failures after combination chemotherapy and radiation therapy for anal canal cancers.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK383ms1yguw%3D%3D&md5=9cd5657f4a0d648a7c36ecf2f845c9e7CAS |

[86]  Ajani JA, Winter KA, Gunderson LL, Pedersen J, Benson AB, Thomas CR, et al Prognostic factors derived from a prospective database dictate clinical biology of anal cancer: the intergroup trial (RTOG 98–11). Cancer 2010; 116 4007–13.
| Prognostic factors derived from a prospective database dictate clinical biology of anal cancer: the intergroup trial (RTOG 98–11).Crossref | GoogleScholarGoogle Scholar |

[87]  Staib L, Gottwald T, Lehnert T, Ruf G, Sturm J, Becker HD, et al Sphincter-saving treatment in epidermoid anal cancer: cooperative analysis of 142 patients in five German university surgical centers. Int J Colorectal Dis 2000; 15 282–90.
| 1:STN:280:DC%2BD3M7ptV2jsg%3D%3D&md5=a8cd3bb63687f93b4d55d55c0b05a550CAS |

[88]  Bonin SR, Pajak TF, Russell AH, Coia LR, Paris KJ, Flam MS, et al Overexpression of p53 protein and outcome of patients treated with chemoradiation for carcinoma of the anal canal: a report of randomized trial RTOG 87–04. Radiation Therapy Oncology Group. Cancer 1999; 85 1226–33.
| Overexpression of p53 protein and outcome of patients treated with chemoradiation for carcinoma of the anal canal: a report of randomized trial RTOG 87–04. Radiation Therapy Oncology Group.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK1M3gtlSjuw%3D%3D&md5=cb78a4cddf45b08c9a165140ef718c42CAS |

[89]  van der Wal BC, Cleffken BI, Gulec B, Kaufman HS, Choti MA. Results of salvage abdominoperineal resection for recurrent anal carcinoma following combined chemoradiation therapy. J Gastrointest Surg 2001; 5 383–7.
| Results of salvage abdominoperineal resection for recurrent anal carcinoma following combined chemoradiation therapy.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD383ksF2gtQ%3D%3D&md5=2fc9284747fa83d9b7620b23ab3d11eeCAS |

[90]  Stewart D, Yan Y, Kodner IJ, Birnbaum E, Fleshman J, Myerson R, et al Salvage surgery after failed chemoradiation for anal canal cancer: should the paradigm be changed for high-risk tumors? J Gastrointest Surg 2007; 11 1744–51.
| Salvage surgery after failed chemoradiation for anal canal cancer: should the paradigm be changed for high-risk tumors?Crossref | GoogleScholarGoogle Scholar |

[91]  Mariani P, Ghanneme A, De la Rochefordiere A, Girodet J, Falcou MC, Salmon RJ. Abdominoperineal resection for anal cancer. Dis Colon Rectum 2008; 51 1495–501.
| Abdominoperineal resection for anal cancer.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD1cnisVGgug%3D%3D&md5=9dcba018ef31f7bbb863903b2f12ff03CAS |

[92]  Ghouti L, Houvenaeghel G, Moutardier V, Giovannini M, Magnin V, Lelong B, et al Salvage abdominoperineal resection after failure of conservative treatment in anal epidermoid cancer. Dis Colon Rectum 2005; 48 16–22.
| Salvage abdominoperineal resection after failure of conservative treatment in anal epidermoid cancer.Crossref | GoogleScholarGoogle Scholar |

[93]  Papaconstantinou HT, Bullard KM, Rothenberger DA, Madoff RD. Salvage abdominoperineal resection after failed Nigro protocol: modest success, major morbidity. Colorectal Dis 2006; 8 124–9.
| Salvage abdominoperineal resection after failed Nigro protocol: modest success, major morbidity.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD28%2FisFKqtg%3D%3D&md5=d64dd8a2fb0769833190bab29c59674eCAS |

[94]  Allal AS, Laurencet FM, Reymond MA, Kurtz JM, Marti MC. Effectiveness of surgical salvage therapy for patients with locally uncontrolled anal carcinoma after sphincter-conserving treatment. Cancer 1999; 86 405–9.
| Effectiveness of surgical salvage therapy for patients with locally uncontrolled anal carcinoma after sphincter-conserving treatment.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK1MzlsleitA%3D%3D&md5=779978fbb3ee85577f655997b53966f9CAS |

[95]  Pocard M, Tiret E, Nugent K, Dehni N, Parc R. Results of salvage abdominoperineal resection for anal cancer after radiotherapy. Dis Colon Rectum 1998; 41 1488–93.
| Results of salvage abdominoperineal resection for anal cancer after radiotherapy.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK1M%2FnsFKksg%3D%3D&md5=a65871cc7b7e93fc9c452025a5a0fe57CAS |

[96]  Buchs NC, Allal AS, Morel P, Gervaz P. Prevention, chemoradiation and surgery for anal cancer. Expert Rev Anticancer Ther 2009; 9 483–9.
| Prevention, chemoradiation and surgery for anal cancer.Crossref | GoogleScholarGoogle Scholar |

[97]  National Cancer Institute (NCI). Anal cancer treatment (PDQ). Bethesda: NCI; 2011. Available online at: http://www.cancer.gov/cancertopics/pdq/treatment/anal/HealthProfessional/page6 [verified October 2011].

[98]  Papillon J, Montbarbon JF. Epidermoid carcinoma of the anal canal. A series of 276 cases. Dis Colon Rectum 1987; 30 324–33.
| Epidermoid carcinoma of the anal canal. A series of 276 cases.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaL2s7ovFCqsQ%3D%3D&md5=3da3b631c9157719fbfc6ed082df27b5CAS |

[99]  Gerard JP, Chapet O, Samiei F, Morignat E, Isaac S, Paulin C, et al 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.
| 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.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD3MzovVyisA%3D%3D&md5=ee430a58b8ab0c495cef0a7a00960921CAS |

[100]  Damin DC, Rosito MA, Schwartsmann G. Sentinel lymph node in carcinoma of the anal canal: a review. Eur J Surg Oncol 2006; 32 247–52.
| Sentinel lymph node in carcinoma of the anal canal: a review.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD287lvF2mtA%3D%3D&md5=c0ac631709819fbe68939c8987e5e2c4CAS |

[101]  Shank B. Treatment of anal canal carcinoma. Cancer 1985; 55 2156–62.
| Treatment of anal canal carcinoma.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaL2M7ltFKksw%3D%3D&md5=df4c3ac98b9b36476fce2dd48159d4fdCAS |

[102]  de Jong JS, Beukema JC, van Dam GM, Slart R, Lemstra C, Wiggers T. Limited value of staging squamous cell carcinoma of the anal margin and canal using the sentinel lymph node procedure: a prospective study with long-term follow-up. Ann Surg Oncol 2010; 17 2656–62.
| Limited value of staging squamous cell carcinoma of the anal margin and canal using the sentinel lymph node procedure: a prospective study with long-term follow-up.Crossref | GoogleScholarGoogle Scholar |

[103]  Glynne-Jones R, Northover JM, Cervantes A. ESMO Guidelines Working Group. Anal cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 2010; 21 v87–92.
| ESMO Guidelines Working Group. Anal cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up.Crossref | GoogleScholarGoogle Scholar |

[104]  Wade DS, Herrera L, Castillo NB, Petrelli NJ. Metastases to the lymph nodes in epidermoid carcinoma of the anal canal studied by a clearing technique. Surg Gynecol Obstet 1989; 169 238–42.
| 1:STN:280:DyaL1MzmvFWlug%3D%3D&md5=47ebb7cb028ba72eb51f93db46becf46CAS |

[105]  Rousseau DL, Thomas CR, Petrelli NJ, Kahlenberg MS. Squamous cell carcinoma of the anal canal. Surg Oncol 2005; 14 121–32.
| Squamous cell carcinoma of the anal canal.Crossref | GoogleScholarGoogle Scholar |

[106]  Licitra L, Spinazze S, Doci R, Evans TR, Tanum G, Ducreux M. Cancer of the anal region. Crit Rev Oncol Hematol 2002; 43 77–92.
| Cancer of the anal region.Crossref | GoogleScholarGoogle Scholar |

[107]  Tokar M, Bobilev D, Zalmanov S, Geffen DB, Walfisch S. Combined multimodal approach to the treatment of metastatic anal carcinoma: report of a case and review of the literature. Onkologie 2006; 29 30–2.
| Combined multimodal approach to the treatment of metastatic anal carcinoma: report of a case and review of the literature.Crossref | GoogleScholarGoogle Scholar |

[108]  Darragh TM, Winkler B. Anal cancer and cervical cancer screening: key differences. Cancer Cytopathol 2011; 119 5–19.
| Anal cancer and cervical cancer screening: key differences.Crossref | GoogleScholarGoogle Scholar |

[109]  Chin-Hong PV, Palefsky JM. Natural history and clinical management of anal human papillomavirus disease in men and women infected with human immunodeficiency virus. Clin Infect Dis 2002; 35 1127–34.
| Natural history and clinical management of anal human papillomavirus disease in men and women infected with human immunodeficiency virus.Crossref | GoogleScholarGoogle Scholar |

[110]  Gillison ML, Chaturvedi AK, Lowy DR. HPV prophylactic vaccines and the potential prevention of noncervical cancers in both men and women. Cancer 2008; 113 3036–46.
| HPV prophylactic vaccines and the potential prevention of noncervical cancers in both men and women.Crossref | GoogleScholarGoogle Scholar |