Download PDF
Clin Colon Rectal Surg
DOI: 10.1055/s-0045-1809890
Review Article

Treatment Options for Anal Neoplasia: Going from Anal Dysplasia to Anal Cancer

Trista J. Stankowski
1   Division of Surgery, Department of Colorectal Surgery, Indiana University Health, Indianapolis, Indiana
› Author Affiliations
› Further Information
Also available at
   Permissions and Reprints

Abstract

While overall uncommon, the incidence of anal cancer in the United States is on the rise. The majority of these cases are squamous cell in origin and attributed to infection with human papillomavirus (HPV) and the associated evolution of anal squamous intraepithelial lesions. Immunosuppressed patients such as those with human immunodeficiency virus (HIV) or solid organ transplants and those with high-grade dysplasia or carcinoma of the cervix or vulva are at highest risk for evolution to anal cancer. The recently published anal cancer HSIL outcomes research (ANCHOR) trial demonstrated benefit to treating anal high-grade squamous intraepithelial lesions (HSILs) to reduce the progression to anal cancer. This article reviews screening and treatment of anal HSIL including ablative, topical, and surgical options as well as the diagnosis and treatment of anal cancer.

Keywords

HSIL - anal dysplasia - anal cancer - HPV


Publication History

Article published online:
02 July 2025

© 2025. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 

  • References

  • 1 Deshmukh AA, Suk R, Shiels MS. et al. Recent trends in squamous cell carcinoma of the anus incidence and mortality in the United States, 2001-2015. J Natl Cancer Inst 2020; 112 (08) 829-838
    CrossrefPubMedSearch in Google Scholar
  • 2 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
    PubMedSearch in Google Scholar
  • 3 Johnson LG, Madeleine MM, Newcomer LM, Schwartz SM, Daling JR. Anal cancer incidence and survival: The surveillance, epidemiology, and end results experience, 1973-2000. Cancer 2004; 101 (02) 281-288
    PubMedSearch in Google Scholar
  • 4 Nelson RA, Levine AM, Bernstein L, Smith DD, Lai LL. Changing patterns of anal canal carcinoma in the United States. J Clin Oncol 2013; 31 (12) 1569-1575
    PubMedSearch in Google Scholar
  • 5 American Cancer Society. Cancer Facts & Figures 2024. 2024.
    PubMed
  • 6 Saraiya M, Unger ER, Thompson TD. et al.; HPV Typing of Cancers Workgroup. US assessment of HPV types in cancers: Implications for current and 9-valent HPV vaccines. J Natl Cancer Inst 2015; 107 (06) djv086
    PubMedSearch in Google Scholar
  • 7 Berry JM, Jay N, Cranston RD. et al. 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 (05) 1147-1155
    PubMedSearch in Google Scholar
  • 8 Stier EA, Clarke MA, Deshmukh AA. et al. International Anal Neoplasia Society's consensus guidelines for anal cancer screening. Int J Cancer 2024; 154 (10) 1694-1702
    CrossrefPubMedSearch in Google Scholar
  • 9 Palefsky JM, Lee JY, Jay N. et al.; ANCHOR Investigators Group. Treatment of anal high-grade squamous intraepithelial lesions to prevent anal cancer. N Engl J Med 2022; 386 (24) 2273-2282
    CrossrefPubMedSearch in Google Scholar
  • 10 Hillman RJ, Cuming T, Darragh T. et al. 2016 IANS International Guidelines for practice standards in the detection of anal cancer precursors. J Low Genit Tract Dis 2016; 20 (04) 283-291
    PubMedSearch in Google Scholar
  • 11 Cho SD, Groves E, Lao VV. History of high-resolution anoscopy. Clin Colon Rectal Surg 2018; 31 (06) 336-346
    PubMedSearch in Google Scholar
  • 12 Burgos J, Curran A, Garcia J. et al. Effectiveness of electrocautery, topical cidofovir, and topical sinecatechins for the treatment of anal high-grade squamous intraepithelial lesions in persons with human immunodeficiency virus: An open-label, randomized controlled trial. Clin Infect Dis 2025; (E-pub ahead of print)
    CrossrefPubMedSearch in Google Scholar
  • 13 Richel O, de Vries HJ, van Noesel CJ, Dijkgraaf MG, 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 (04) 346-353
    CrossrefPubMedSearch in Google Scholar
  • 14 Brogden DRL, Walsh U, Pellino G, Kontovounisios C, Tekkis P, Mills SC. Evaluating the efficacy of treatment options for anal intraepithelial neoplasia: A systematic review. Int J Colorectal Dis 2021; 36 (02) 213-226
    PubMedSearch in Google Scholar
  • 15 Mir M. Electrocautery. MedScape. July 1, 2022. Accessed March 20, 2025 at: https://emedicine.medscape.com/article/2111163-overview?form=fpf
    PubMed
  • 16 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. J Acquir Immune Defic Syndr 2012; 59 (03) 259-265
    PubMedSearch in Google Scholar
  • 17 Terlizzi JP, Goldstone SE. Ablative therapies for the treatment of anal high-grade squamous intraepithelial lesions. Semin Colon Rectal Surg 2017; 28 (02) 81-85
    PubMedSearch in Google Scholar
  • 18 Corral J, Parés D, García-Cuyás F. et al. Clinical results of infrared coagulation as a treatment of high-grade anal dysplasia: A systematic review. Tech Coloproctol 2019; 23 (08) 707-712
    PubMedSearch in Google Scholar
  • 19 Nathan M, Hickey N, Mayuranathan L, Vowler SL, Singh N. Treatment of anal human papillomavirus-associated disease: A long term outcome study. Int J STD AIDS 2008; 19 (07) 445-449
    PubMedSearch in Google Scholar
  • 20 Vergara-Fernandez O, Solórzano-Vicuña D, Coss-Adame E, Trejo-Avila M. Outcomes of radiofrequency ablation for anal high-grade squamous intraepithelial lesions. Tech Coloproctol 2021; 25 (06) 701-707
    PubMedSearch in Google Scholar
  • 21 Megill C, Wilkin T. Topical therapies for the treatment of anal high-grade squamous intraepithelial lesions. Semin Colon Rectal Surg 2017; 28 (02) 86-90
    CrossrefPubMedSearch in Google Scholar
  • 22 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 (07) 420-426
    PubMedSearch in Google Scholar
  • 23 Singh J, Kuohung V, Palefsky J. 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 (04) 474-479 . Erratum in J Acquir Immune Defic Syndr 2012;60(3):e105–e106 .
    PubMedSearch in Google Scholar
  • 24 Stier EA, Goldstone SE, Einstein MH. et al. Safety and efficacy of topical cidofovir to treat high-grade perianal and vulvar intraepithelial neoplasia in HIV-positive men and women. AIDS 2013; 27 (04) 545-551
    PubMedSearch in Google Scholar
  • 25 Burgos J, Campany D, Garcia J, Landolfi S, Falcó V, Curran A. Effectiveness of topical cidofovir for treatment of refractory anal high-grade squamous intraepithelial lesion. AIDS 2023; 37 (09) 1425-1429
    PubMedSearch in Google Scholar
  • 26 Beck DE, Fazio VW, Jagelman DG, Lavery IC. Perianal Bowen's disease. Dis Colon Rectum 1988; 31 (06) 419-422
    PubMedSearch in Google Scholar
  • 27 Strauss RJ, Fazio VW. Bowen's disease of the anal and perianal area. A report and analysis of twelve cases. Am J Surg 1979; 137 (02) 231-234
    PubMedSearch in Google Scholar
  • 28 Marchesa P, Fazio VW, Oliart S, Goldblum JR, Lavery IC. Perianal Bowen's disease: A clinicopathologic study of 47 patients. Dis Colon Rectum 1997; 40 (11) 1286-1293
    PubMedSearch in Google Scholar
  • 29 Siddharthan RV, Lanciault C, Tsikitis VL. Anal intraepithelial neoplasia: Diagnosis, screening, and treatment. Ann Gastroenterol 2019; 32 (03) 257-263
    PubMedSearch in Google Scholar
  • 30 Pineda CE, Welton ML. Management of anal squamous intraepithelial lesions. Clin Colon Rectal Surg 2009; 22 (02) 94-101
    PubMedSearch in Google Scholar
  • 31 Sands D, Mahmoud N. Anal cancer. In: The ASCRS Textbook of Colon and Rectal Surgery. 4th ed.. Springer Nature Switzerland AG; 2022.
  • 32 National Comprehensive Cancer Network. NCCN Guidelines Version 3. Anal Carcinoma. 2025. Accessed April 24, 2025 at: https://www.nccn.org/professionals/physician_gls/pdf/anal.pdf
    PubMed
  • 33 Nigro ND, Vaitkevicius VK, Considine B. Combined therapy for cancer of the anal canal: a preliminary report. Dis Colon Rectum 1993; 36 (07) 709-711
    PubMedSearch in Google Scholar
  • 34 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
    CrossrefPubMedSearch in Google Scholar
  • 35 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
    CrossrefPubMedSearch in Google Scholar
  • 36 Goodman KA, Julie D, Cercek A. et al. Capecitabine with mitomycin reduces acute hematologic toxicity and treatment delays in patients undergoing definitive chemoradiation using intensity modulated radiation therapy for anal cancer. Int J Radiat Oncol Biol Phys 2017; 98 (05) 1087-1095
    PubMedSearch in Google Scholar
  • 37 Thind G, Johal B, Follwell M, Kennecke HF. Chemoradiation with capecitabine and mitomycin-C for stage I-III anal squamous cell carcinoma. Radiat Oncol 2014; 9: 124
    PubMedSearch in Google Scholar
  • 38 Pepek JM, Willett CG, Czito BG. Radiation therapy advances for treatment of anal cancer. J Natl Compr Canc Netw 2010; 8 (01) 123-129
    PubMedSearch in Google Scholar
  • 39 Goodman KA, Gollub MJ, Eng C. et al. AJCC Cancer Staging System Version 9: Anus. In: Amin MB, Edge S. eds. AJCC Cancer Staging Manual. 9th ed. Chicago, IL: American Joint Committee on Cancer; 2022
    Search in Google Scholar