Download PDF
Clin Colon Rectal Surg 2018; 31(06): 353-360
DOI: 10.1055/s-0038-1668105
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

So Now My Patient Has Squamous Cell Cancer: Diagnosis, Staging, and Treatment of Squamous Cell Carcinoma of the Anal Canal and Anal Margin

Cindy Kin
1   Department of Surgery, Stanford University School of Medicine, Stanford, California
› Author Affiliations
Further Information

Publication History

Publication Date:
02 November 2018 (online)

    Permissions and Reprints

Abstract

Squamous cell carcinomas of the anal canal and the anal margin are rare malignancies that are increasing in incidence. Patients with these tumors often experience delayed treatment due to delay in diagnosis or misdiagnosis of the condition. Distinguishing between anal canal and anal margin tumors has implications for staging and treatment. Chemoradiation therapy is the mainstay of treatment for anal canal squamous cell, with abdominoperineal resection reserved for salvage treatment in cases of persistent or recurrent disease. Early anal margin squamous cell carcinoma can be treated with wide local excision, but more advanced tumors require a combination of chemoradiation therapy and surgical excision.

Keywords

anal squamous cell carcinoma - chemoradiation - abdominoperineal resection - wide local excision
 

  • References

  • 1 Shiels MS, Kreimer AR, Coghill AE, Darragh TM, Devesa SS. Anal cancer incidence in the United States, 1977-2011: distinct patterns by histology and behavior. Cancer Epidemiol Biomarkers Prev 2015; 24 (10) 1548-1556
    CrossrefPubMedGoogle Scholar
  • 2 Winburn GB. Anal carcinoma or “just hemorrhoids”?. Am Surg 2001; 67 (11) 1048-1058
    PubMedGoogle Scholar
  • 3 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 (19) 1350-1358
    CrossrefPubMedGoogle Scholar
  • 4 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 (18) 1500-1510
    CrossrefPubMedGoogle Scholar
  • 5 Meeuwis KA, Melchers WJ, Bouten H. , et al. Anogenital malignancies in women after renal transplantation over 40 years in a single center. Transplantation 2012; 93 (09) 914-922
    CrossrefPubMedGoogle Scholar
  • 6 Penn I. Cancers of the anogenital region in renal transplant recipients. Analysis of 65 cases. Cancer 1986; 58 (03) 611-616
    CrossrefPubMedGoogle Scholar
  • 7 Welton ML, Sharkey FE, Kahlenberg MS. The etiology and epidemiology of anal cancer. Surg Oncol Clin N Am 2004; 13 (02) 263-275
    CrossrefPubMedGoogle Scholar
  • 8 Werness BA, Levine AJ, Howley PM. Association of human papillomavirus types 16 and 18 E6 proteins with p53. Science 1990; 248 (4951): 76-79
    CrossrefPubMedGoogle Scholar
  • 9 Pecoraro G, Morgan D, Defendi V. Differential effects of human papillomavirus type 6, 16, and 18 DNAs on immortalization and transformation of human cervical epithelial cells. Proc Natl Acad Sci U S A 1989; 86 (02) 563-567
    CrossrefPubMedGoogle Scholar
  • 10 Palefsky JM, Holly EA, Gonzales J, Berline J, Ahn DK, Greenspan JS. Detection of human papillomavirus DNA in anal intraepithelial neoplasia and anal cancer. Cancer Res 1991; 51 (03) 1014-1019
    PubMedGoogle Scholar
  • 11 zur Hausen H. Papillomaviruses causing cancer: evasion from host-cell control in early events in carcinogenesis. J Natl Cancer Inst 2000; 92 (09) 690-698
    CrossrefPubMedGoogle Scholar
  • 12 Strickler HD, Schiffman MH. Is human papillomavirus an infectious cause of non-cervical anogenital tract cancers?. BMJ 1997; 315 (7109): 620-621
    CrossrefPubMedGoogle Scholar
  • 13 Burgi A, Brodine S, Wegner S. , et al. Incidence and risk factors for the occurrence of non-AIDS-defining cancers among human immunodeficiency virus-infected individuals. Cancer 2005; 104 (07) 1505-1511
    CrossrefPubMedGoogle Scholar
  • 14 Clifford GM, Polesel J, Rickenbach M. , et al; Swiss HIV Cohort. Cancer risk in the Swiss HIV Cohort Study: associations with immunodeficiency, smoking, and highly active antiretroviral therapy. J Natl Cancer Inst 2005; 97 (06) 425-432
    CrossrefPubMedGoogle Scholar
  • 15 Crum-Cianflone NF, Hullsiek KH, Marconi V. , et al. The impact of nelfinavir exposure on cancer development among a large cohort of HIV-infected patients. J Acquir Immune Defic Syndr 2009; 51 (03) 305-309
    CrossrefPubMedGoogle Scholar
  • 16 Patel HS, Silver AR, Northover JM. Anal cancer in renal transplant patients. Int J Colorectal Dis 2007; 22 (01) 1-5
    CrossrefPubMedGoogle Scholar
  • 17 Skov Dalgaard L, Fassel U, Østergaard LJ, Jespersen B, Schmeltz Søgaard O, Jensen-Fangel S. Risk of human papillomavirus-related cancers among kidney transplant recipients and patients receiving chronic dialysis--an observational cohort study. BMC Nephrol 2013; 14: 137
    CrossrefPubMedGoogle Scholar
  • 18 Daling JR, Sherman KJ, Hislop TG. , et al. Cigarette smoking and the risk of anogenital cancer. Am J Epidemiol 1992; 135 (02) 180-189
    CrossrefPubMedGoogle Scholar
  • 19 Holly EA, Whittemore AS, Aston DA, Ahn DK, Nickoloff BJ, Kristiansen JJ. Anal cancer incidence: genital warts, anal fissure or fistula, hemorrhoids, and smoking. J Natl Cancer Inst 1989; 81 (22) 1726-1731
    CrossrefPubMedGoogle Scholar
  • 20 Rickert RR, Compton CC. ; Cancer Committee of the College of American Pathologists. Protocol for the examination of specimens from patients with carcinomas of the anus and anal canal: a basis for checklists. Arch Pathol Lab Med 2000; 124 (01) 21-25
    PubMedGoogle Scholar
  • 21 Edge S, Byrd D, Compton C, Fritz A, Greene F, Trotti A. , eds. Anus. In: AJCC Cancer Staging Manual, 7th edition. New York, NY: Springer; 2011: 163-174
    Google Scholar
  • 22 Edge S, Byrd D, Compton C, Fritz A, Greene F, Trotti A. , eds. Cutaneous squamous cell carcinoma and other cutaneous carcinomas. AJCC Cancer Staging Manual, 7th edition. Springer; 2011: 301-314
    Google Scholar
  • 23 Otto SD, Lee L, Buhr HJ, Frericks B, Höcht S, Kroesen AJ. Staging anal cancer: prospective comparison of transanal endoscopic ultrasound and magnetic resonance imaging. J Gastrointest Surg 2009; 13 (07) 1292-1298
    CrossrefPubMedGoogle Scholar
  • 24 Christensen AF, Nielsen MB, Engelholm SA, Roed H, Svendsen LB, Christensen H. Three-dimensional anal endosonography may improve staging of anal cancer compared with two-dimensional endosonography. Dis Colon Rectum 2004; 47 (03) 341-345
    CrossrefPubMedGoogle Scholar
  • 25 Christensen AF, Nyhuus B, Nielsen MB. Interobserver and intraobserver variation of two-dimensional and three-dimensional anal endosonography in the evaluation of recurrent anal cancer. Dis Colon Rectum 2009; 52 (03) 484-488
    CrossrefPubMedGoogle Scholar
  • 26 Damin DC, Rosito MA, Schwartsmann G. Sentinel lymph node in carcinoma of the anal canal: a review. Eur J Surg Oncol 2006; 32 (03) 247-252
    CrossrefPubMedGoogle Scholar
  • 27 Gretschel S, Warnick P, Bembenek A. , et al. Lymphatic mapping and sentinel lymph node biopsy in epidermoid carcinoma of the anal canal. Eur J Surg Oncol 2008; 34 (08) 890-894
    CrossrefPubMedGoogle Scholar
  • 28 Ulmer C, Bembenek A, Gretschel S. , et al. Sentinel node biopsy in anal cancer - a promising strategy to individualize therapy. Onkologie 2003; 26 (05) 456-460
    PubMedGoogle Scholar
  • 29 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 (02) 365-370
    CrossrefPubMedGoogle Scholar
  • 30 Mistrangelo M, Pelosi E, Bellò M. , 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 (01) 73-78
    CrossrefPubMedGoogle Scholar
  • 31 Touboul E, Schlienger M, Buffat L. , et al. Epidermoid carcinoma of the anal canal. Results of curative-intent radiation therapy in a series of 270 patients. Cancer 1994; 73 (06) 1569-1579
    CrossrefPubMedGoogle Scholar
  • 32 Deniaud-Alexandre E, Touboul E, Tiret E. , et al. Results of definitive irradiation in a series of 305 epidermoid carcinomas of the anal canal. Int J Radiat Oncol Biol Phys 2003; 56 (05) 1259-1273
    CrossrefPubMedGoogle Scholar
  • 33 Nigro ND, Vaitkevicius VK, Considine Jr B. Combined therapy for cancer of the anal canal: a preliminary report. Dis Colon Rectum 1974; 17 (03) 354-356
    CrossrefPubMedGoogle Scholar
  • 34 Buroker TR, Nigro N, Bradley G. , et al. Combined therapy for cancer of the anal canal: a follow-up report. Dis Colon Rectum 1977; 20 (08) 677-678
    CrossrefPubMedGoogle Scholar
  • 35 Nigro ND. An evaluation of combined therapy for squamous cell cancer of the anal canal. Dis Colon Rectum 1984; 27 (12) 763-766
    CrossrefPubMedGoogle Scholar
  • 36 Nigro ND. Multidisciplinary management of cancer of the anus. World J Surg 1987; 11 (04) 446-451
    CrossrefPubMedGoogle Scholar
  • 37 Newman HK, Quan SH. Multi-modality therapy for epidermoid carcinoma of the anus. Cancer 1976; 37 (01) 12-19
    CrossrefPubMedGoogle Scholar
  • 38 Roelofsen F, Bartelink H. Combined modality treatment of anal carcinoma. Oncologist 1998; 3 (06) 413-418
    PubMedGoogle Scholar
  • 39 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 (09) 2527-2539
    CrossrefPubMedGoogle Scholar
  • 40 Sischy B, Doggett RL, Krall JM. , et al. Definitive irradiation and chemotherapy for radiosensitization in management of anal carcinoma: interim report on Radiation Therapy Oncology Group study no. 8314. J Natl Cancer Inst 1989; 81 (11) 850-856
    CrossrefPubMedGoogle Scholar
  • 41 Cummings BJ, Keane TJ, O'Sullivan B, Wong CS, Catton CN. Epidermoid anal cancer: treatment by radiation alone or by radiation and 5-fluorouracil with and without mitomycin C. Int J Radiat Oncol Biol Phys 1991; 21 (05) 1115-1125
    CrossrefPubMedGoogle Scholar
  • 42 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 (9034): 1049-1054
    CrossrefPubMedGoogle Scholar
  • 43 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 (05) 2040-2049
    CrossrefPubMedGoogle Scholar
  • 44 Balamucki CJ, Zlotecki RA, Rout WR. , et al. Squamous cell carcinoma of the anal margin: the University of Florida experience. Am J Clin Oncol 2011; 34 (04) 406-410
    CrossrefPubMedGoogle Scholar
  • 45 Rabbani AN, Zlotecki RA, Kirwan J. , et al. Definitive radiotherapy for squamous cell carcinoma of the anal canal. Am J Clin Oncol 2010; 33 (01) 47-51
    CrossrefPubMedGoogle Scholar
  • 46 Ajani JA, Winter KA, Gunderson LL. , et al. Fluorouracil, mitomycin, and radiotherapy vs fluorouracil, cisplatin, and radiotherapy for carcinoma of the anal canal: a randomized controlled trial. JAMA 2008; 299 (16) 1914-1921
    CrossrefPubMedGoogle Scholar
  • 47 Gunderson LL, Winter KA, Ajani JA. , et al. 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 (35) 4344-4351
    CrossrefPubMedGoogle Scholar
  • 48 James RD, Glynne-Jones R, Meadows HM. , et al. 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 (06) 516-524
    CrossrefPubMedGoogle Scholar
  • 49 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 (10) 2656-2662
    CrossrefPubMedGoogle Scholar
  • 50 Kachnic LA, Winter K, Myerson RJ. , et al. 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 (01) 27-33
    CrossrefPubMedGoogle Scholar
  • 51 Han K, Cummings BJ, Lindsay P. , et al. 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 (03) 587-594
    PubMedGoogle Scholar
  • 52 Mitchell MP, Abboud M, Eng C. , et al. Intensity-modulated radiation therapy with concurrent chemotherapy for anal cancer: outcomes and toxicity. Am J Clin Oncol 2014; 37 (05) 461-466
    CrossrefPubMedGoogle Scholar
  • 53 Salama JK, Mell LK, Schomas DA. , et al. Concurrent chemotherapy and intensity-modulated radiation therapy for anal canal cancer patients: a multicenter experience. J Clin Oncol 2007; 25 (29) 4581-4586
    CrossrefPubMedGoogle Scholar
  • 54 Tomasoa NB, Meulendijks D, Nijkamp J, Cats A, Dewit L. Clinical outcome in patients treated with simultaneous integrated boost - intensity modulated radiation therapy (SIB-IMRT) with and without concurrent chemotherapy for squamous cell carcinoma of the anal canal. Acta Oncol 2016; 55 (06) 760-766
    CrossrefPubMedGoogle Scholar
  • 55 Glynne-Jones R, Nilsson PJ, Aschele C. , et al; European Society for Medical Oncology (ESMO); European Society of Surgical Oncology (ESSO); European Society of Radiotherapy and Oncology (ESTRO). Anal cancer: ESMO-ESSO-ESTRO clinical practice guidelines for diagnosis, treatment and follow-up. Eur J Surg Oncol 2014; 40 (10) 1165-1176
    CrossrefPubMedGoogle Scholar
  • 56 Peterson CY, Weiser MR, Paty PB. , et al. Does endoscopic ultrasound improve detection of locally recurrent anal squamous-cell cancer?. Dis Colon Rectum 2015; 58 (02) 193-198
    CrossrefPubMedGoogle Scholar
  • 57 Christensen AF, Nielsen MB, Svendsen LB, Engelholm SA. Three-dimensional anal endosonography may improve detection of recurrent anal cancer. Dis Colon Rectum 2006; 49 (10) 1527-1532
    CrossrefPubMedGoogle Scholar
  • 58 Lund JA, Sundstrom SH, Haaverstad R, Wibe A, Svinsaas M, Myrvold HE. Endoanal ultrasound is of little value in follow-up of anal carcinomas. Dis Colon Rectum 2004; 47 (06) 839-842
    CrossrefPubMedGoogle Scholar
  • 59 Martellucci J, Naldini G, Colosimo C, Cionini L, Rossi M. Accuracy of endoanal ultrasound in the follow-up assessment for squamous cell carcinoma of the anal canal treated with radiochemotherapy. Surg Endosc 2009; 23 (05) 1054-1057
    CrossrefPubMedGoogle Scholar
  • 60 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 (01) 68-77
    CrossrefPubMedGoogle Scholar
  • 61 Lefevre JH, Parc Y, Kernéis S. , et al. Abdomino-perineal resection for anal cancer: impact of a vertical rectus abdominis myocutaneus flap on survival, recurrence, morbidity, and wound healing. Ann Surg 2009; 250 (05) 707-711
    CrossrefPubMedGoogle Scholar
  • 62 Lefèvre JH, Corte H, Tiret E. , et al. Abdominoperineal resection for squamous cell anal carcinoma: survival and risk factors for recurrence. Ann Surg Oncol 2012; 19 (13) 4186-4192
    CrossrefPubMedGoogle Scholar
  • 63 Mullen JT, Rodriguez-Bigas MA, Chang GJ. , et al. Results of surgical salvage after failed chemoradiation therapy for epidermoid carcinoma of the anal canal. Ann Surg Oncol 2007; 14 (02) 478-483
    CrossrefPubMedGoogle Scholar
  • 64 Akbari RP, Paty PB, Guillem JG. , et al. Oncologic outcomes of salvage surgery for epidermoid carcinoma of the anus initially managed with combined modality therapy. Dis Colon Rectum 2004; 47 (07) 1136-1144
    CrossrefPubMedGoogle Scholar
  • 65 Severino NP, Chadi SA, Rosen L. , et al. Survival following salvage abdominoperineal resection for persistent and recurrent squamous cell carcinoma of the anus: do these disease categories affect survival?. Colorectal Dis 2016; 18 (10) 959-966
    CrossrefPubMedGoogle Scholar
  • 66 Schiller DE, Cummings BJ, Rai S. , et al. Outcomes of salvage surgery for squamous cell carcinoma of the anal canal. Ann Surg Oncol 2007; 14 (10) 2780-2789
    CrossrefPubMedGoogle Scholar
  • 67 Chapet O, Gerard JP, Mornex F. , et al. Prognostic factors of squamous cell carcinoma of the anal margin treated by radiotherapy: the Lyon experience. Int J Colorectal Dis 2007; 22 (02) 191-199
    PubMedGoogle Scholar
  • 68 Greenall MJ, Quan SH, Stearns MW, Urmacher C, DeCosse JJ. Epidermoid cancer of the anal margin. Pathologic features, treatment, and clinical results. Am J Surg 1985; 149 (01) 95-101
    CrossrefPubMedGoogle Scholar
  • 69 Jensen SL, 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 (04) 273-278
    CrossrefPubMedGoogle Scholar
  • 70 Papillon J, Chassard JL. Respective roles of radiotherapy and surgery in the management of epidermoid carcinoma of the anal margin. Series of 57 patients. Dis Colon Rectum 1992; 35 (05) 422-429
    CrossrefPubMedGoogle Scholar
  • 71 Grabenbauer GG, Kessler H, Matzel KE, Sauer R, Hohenberger W, Schneider IH. Tumor site predicts outcome after radiochemotherapy in squamous-cell carcinoma of the anal region: long-term results of 101 patients. Dis Colon Rectum 2005; 48 (09) 1742-1751
    CrossrefPubMedGoogle Scholar
  • 72 Khanfir K, Ozsahin M, Bieri S, Cavuto C, Mirimanoff RO, Zouhair A. Patterns of failure and outcome in patients with carcinoma of the anal margin. Ann Surg Oncol 2008; 15 (04) 1092-1098
    CrossrefPubMedGoogle Scholar
  • 73 Bieri S, Allal AS, Kurtz JM. Sphincter-conserving treatment of carcinomas of the anal margin. Acta Oncol 2001; 40 (01) 29-33
    CrossrefPubMedGoogle Scholar
  • 74 Kent C, Bessell EM, Scholefield JH. , et al. Chemoradiotherapy with brachytherapy or electron therapy boost for locally advanced squamous cell carcinoma of the anus-reducing the colostomy rate. J Gastrointest Cancer 2017; 48 (01) 1-7
    CrossrefPubMedGoogle Scholar
  • 75 Seo Y, Kinsella MT, Reynolds HL, Chipman G, Remick SC, Kinsella TJ. Outcomes of chemoradiotherapy with 5-Fluorouracil and mitomycin C for anal cancer in immunocompetent versus immunodeficient patients. Int J Radiat Oncol Biol Phys 2009; 75 (01) 143-149
    CrossrefPubMedGoogle Scholar
  • 76 Fraunholz IB, Haberl A, Klauke S, Gute P, Rödel CM. Long-term effects of chemoradiotherapy for anal cancer in patients with HIV infection: oncological outcomes, immunological status, and the clinical course of the HIV disease. Dis Colon Rectum 2014; 57 (04) 423-431
    CrossrefPubMedGoogle Scholar
  • 77 Fraunholz I, Weiss C, Eberlein K, Haberl A, Rödel C. Concurrent chemoradiotherapy with 5-fluorouracil and mitomycin C for invasive anal carcinoma in human immunodeficiency virus-positive patients receiving highly active antiretroviral therapy. Int J Radiat Oncol Biol Phys 2010; 76 (05) 1425-1432
    CrossrefPubMedGoogle Scholar
  • 78 Berry JM, Palefsky JM, Welton ML. Anal cancer and its precursors in HIV-positive patients: perspectives and management. Surg Oncol Clin N Am 2004; 13 (02) 355-373
    CrossrefPubMedGoogle Scholar
  • 79 Wexler A, Berson AM, Goldstone SE. , et al. Invasive anal squamous-cell carcinoma in the HIV-positive patient: outcome in the era of highly active antiretroviral therapy. Dis Colon Rectum 2008; 51 (01) 73-81
    CrossrefPubMedGoogle Scholar