Anal Cancer Workup: Approach Considerations, Screening, Staging

Sections

Anal Cancer

Workup

Approach Considerations

Anal cancer is typically found in one of the following three ways:

As an incidental finding on biopsy for another reason
During surveillance for anal intraepithelial neoplasia (AIN; precancerous lesion)
Discovered de novo

Anoscopy and rigid proctoscopy to determine the size of the primary lesion and the extent of the spread of disease will guide preoperative staging. Incisional or punch biopsy of the lesion as well as core needle biopsy of suspected lymph node spread should also be performed. Pap smear testing of the anus and cervix can be performed to document the presence of high-risk serotypes of human papillomavirus (HPV).^[27]

A biopsy result is the first step in the diagnostic algorithm. Rarely, the biopsy will reveal entities other than squamous cell carcinoma, such as the following:

Adenocarcinoma
Melanoma
Gastrointestinal stromal tumor (GIST)
Neuroendocrine tumor
Basal cell carcinoma
Paget disease
Verrucous carcinoma
Kaposi sarcoma
Lymphoma

When biopsy identifies an entity other than squamous cell carcinoma, the subsequent workup will mirror more closely the workup of disease from that entity at other sites in the body.

In patients with anal squamous cell carcinoma, colonoscopy examination is also recommended, as there is a 15% incidence of colorectal neoplasm discovered at the time of diagnosis, though there is no known link between colorectal cancer and anal cancer^[27].

Imaging studies for all anal cancer patients should include a computed tomography (CT) scan of the chest, abdomen, and pelvis to evaluate for enlarged lymph nodes and metastatic spread. Female patients should be evaluated with a thorough gynecologic examination, including screening for cervical cancer. A positron emission tomography (PET)–CT scan can be considered in certain clinical scenarios. HIV testing may be appropriate and is advocated by many authorities, with a CD4 level when indicated.^{[27, 28]}

Screening

Currently, no major regulatory or professional body recommends anal cancer screening for the general population, and controversy surrounds the questions of which patients are candidates for screening and what techniques should be used. Colorectal cancer screening in any form except colonoscopy has little to no likelihood of discovering anal cancer, though a digital rectal examination should be performed when a screening test is ordered or performed. Anal cancer may be discovered during colonoscopy or during the pre-procedure digital rectal examination, but the screening protocols designed for the discovery of colorectal cancer are not designed to discover anal cancer.

In general, screening is recommended in patients at high risk for anal cancer, such as the following:

Some immunocompromised patients (eg, kidney or liver transplant recipients)
Patients with anogenital warts
HIV-positive men who have sex with men (MSM)

The HIV Medicine Association of the Infectious Diseases Society of America (IDSA) recommends screening by anal Papanicolaou (Pap) smear for the following HIV-positive patients^{[29, 30]}:

MSM
Women with a history of receptive anal intercourse or abnormal cervical Pap smear
HIV-positive people with anogenital warts

Possible screening methods for anal cancer and AIN include the following:

Anal Pap smear
High-resolution anoscopy (HRA)
Digital anorectal examination
HPV testing

HRA serves as the gold standard of anal cancer screening. However, it is perhaps prohibitively expensive and poorly implementable.^[31]

Staging

Staging is based on the widely used American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) system, to stratify patients into research, treatment, and survival groupings.^[11]The primary tumor classification is based on size and depth of invasion, nodal status is based on location of the nodes, and metastatic disease is designated as present (M1) or absent (M0).

Primary tumor (T) designations are as follows:

Tis - High-grade squamous intraepithelial lesion (previously termed carcinoma in situ, Bowen disease, anal intraepithelial neoplasia II–III, high-grade anal intraepithelial neoplasia)
T1 - Tumor ≤ 2 cm
T2 - Tumor 2–5 cm
T3 - Tumor > 5 cm
T4 - Any size tumor that invades adjacent organs (eg, vagina, bladder, urethra, but not anal sphincter complex)

Regional lymph node designations are as follows:

N0 - No regional lymph node metastasis
N1 - Metastasis in inguinal, mesorectal, internal iliac, or external iliac nodes
N1a - Metastasis in inguinal, mesorectal, or internal iliac, lymph nodes
N1b - Metastasis in external iliac lymph nodes
N1c - Metastasis in external iliac with any N1a nodes

Metastasis designations are as follows:

M0 - No distant metastasis
M1 - Distant metastasis

Anatomic stage/prognostic groups are listed in the Table below.

Table. Anatomic stage/prognostic group (Open Table in a new window)

Stage	T	N	M
0	Tis	N0	M0
I	T1	N0	M0
IIA	T2	N0	M0
IIB	T3	N0	M0
IIIA	T1-2	N1	M0
IIIB	T4	N0	M0
IIIC	T3-4	N1	M0
IV	Any T	Any N	M1

See also Anal Cancer Staging.

Treatment & Management

PDQ Adult Treatment Editorial Board. Anal Cancer Treatment (PDQ®): Health Professional Version. August 16, 2019. [Medline]. [Full Text].
Welton ML, Lambert R, Bosman FT. Anal Canal. Bosman FT, Carneiro F, Hruban RH, Theise ND. WHO Classification of Tumours of the Digestive System. Lyon: IARC; 2010. 183-193.
de Sanjosé S, Bruni L, Alemany L. HPV in genital cancers (at the exception of cervical cancer) and anal cancers. Presse Med. 2014 Oct 30. 43 (12P2):e423-e428. [Medline].
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 Nov 6. 337 (19):1350-8. [Medline].
Schiffman M, Wentzensen N, Wacholder S, Kinney W, Gage JC, Castle PE. Human papillomavirus testing in the prevention of cervical cancer. J Natl Cancer Inst. 2011 Mar 2. 103 (5):368-83. [Medline].
Bean SM, Chhieng DC. Anal-rectal cytology: a review. Diagn Cytopathol. 2010 Jul. 38 (7):538-46. [Medline].
Scholefield JH, Hickson WG, Smith JH, Rogers K, Sharp F. Anal intraepithelial neoplasia: part of a multifocal disease process. Lancet. 1992 Nov 21. 340 (8830):1271-3. [Medline].
Watson AJ, Smith BB, Whitehead MR, Sykes PH, Frizelle FA. Malignant progression of anal intra-epithelial neoplasia. ANZ J Surg. 2006 Aug. 76 (8):715-7. [Medline].
Crum-Cianflone NF, Hullsiek KH, Marconi VC, Ganesan A, Weintrob A, Barthel RV, et al. Anal cancers among HIV-infected persons: HAART is not slowing rising incidence. AIDS. 2010 Feb 20. 24 (4):535-43. [Medline].
van Seters M, van Beurden M, ten Kate FJ, Beckmann I, Ewing PC, Eijkemans MJ, et al. Treatment of vulvar intraepithelial neoplasia with topical imiquimod. N Engl J Med. 2008 Apr 3. 358 (14):1465-73. [Medline].
American Joint Committee on Cancer. Amin MB, Edge S, Greene F, Byrd DR, Brookland RK, et al, eds. AJCC Cancer Staging Manual. 8th edition. New York: Spinger; 2017.
SEER Stat Fact Sheets: Anal Cancer. NIH Surveillance, Epidemiology and End Results Program. Available at http://seer.cancer.gov/statfacts/html/anus.html. Accessed: December 9, 2019.
Deshmukh AA, Suk R, Shiels MS, Sonawane K, Nyitray AG, Liu Y, et al. Recent trends in squamous cell carcinoma of the anus incidence and mortality in the United States, 2001-2015. J Natl Cancer Inst. 2019 Nov 19. [Medline].
Cancer Facts & Figures 2019. American Cancer Society. Available at https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2019/cancer-facts-and-figures-2019.pdf. Accessed: December 9, 2019.
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019 Jan. 69 (1):7-34. [Medline]. [Full Text].
Grulich AE, Poynten IM, Machalek DA, Jin F, Templeton DJ, Hillman RJ. The epidemiology of anal cancer. Sex Health. 2012 Dec. 9 (6):504-8. [Medline].
Darwich L, Videla S, Cañadas MP, Piñol M, García-Cuyàs F, Vela S, et al. Distribution of human papillomavirus genotypes in anal cytological and histological specimens from HIV-infected men who have sex with men and men who have sex with women. Dis Colon Rectum. 2013 Sep. 56 (9):1043-52. [Medline].
Forman D, de Martel C, Lacey CJ, Soerjomataram I, Lortet-Tieulent J, Bruni L, et al. Global burden of human papillomavirus and related diseases. Vaccine. 2012 Nov 20. 30 Suppl 5:F12-23. [Medline].
Myerson RJ, Karnell LH, Menck HR. The National Cancer Data Base report on carcinoma of the anus. Cancer. 1997 Aug 15. 80 (4):805-15. [Medline].
Jones CM, Goh V, Sebag-Montefiore D, Gilbert DC. Biomarkers in anal cancer: from biological understanding to stratified treatment. Br J Cancer. 2017 Jan 17. 116 (2):156-162. [Medline]. [Full Text].
Ryan DP, Compton CC, Mayer RJ. Carcinoma of the anal canal. N Engl J Med. 2000 Mar 16. 342 (11):792-800. [Medline].
Chiu S, Joseph K, Ghosh S, Cornand RM, Schiller D. Reasons for delays in diagnosis of anal cancer and the effect on patient satisfaction. Can Fam Physician. 2015 Nov. 61 (11):e509-16. [Medline].
Möller C, Saksela E. Cancer of the anus and anal canal. Acta Chir Scand. 1970. 136 (4):340-8. [Medline].
Hiorns LR, Scholefield JH, Palmer JG, Shepherd NA, Kerr IB. Ki-ras oncogene mutations in non-HPV-associated anal carcinoma. J Pathol. 1990 Jun. 161 (2):99-103. [Medline].
Daling JR, Madeleine MM, Johnson LG, Schwartz SM, Shera KA, Wurscher MA, et al. Human papillomavirus, smoking, and sexual practices in the etiology of anal cancer. Cancer. 2004 Jul 15. 101 (2):270-80. [Medline].
Učakar V, Jelen MM, Faust H, Poljak M, Dillner J, Klavs I. Pre-vaccination seroprevalence of 15 human papillomavirus (HPV) types among women in the population-based Slovenian cervical screening program. Vaccine. 2013 Oct 9. 31 (43):4935-9. [Medline].
[Guideline] Steele SR, Varma MG, Melton GB, Ross HM, Rafferty JF, Buie WD, et al. Practice parameters for anal squamous neoplasms. Dis Colon Rectum. 2012 Jul. 55 (7):735-49. [Medline]. [Full Text].
[Guideline] NCCN Clinical Practice Guidelines in Oncology: Anal Carcinoma. NCCN.org. Available at https://www.nccn.org/professionals/physician_gls/f_guidelines.asp#anal. Version 1.2020 — November 19, 2019; Accessed: December 20, 2019.
Leeds IL, Fang SH. Anal cancer and intraepithelial neoplasia screening: A review. World J Gastrointest Surg. 2016 Jan 27. 8 (1):41-51. [Medline].
[Guideline] Aberg JA, Gallant JE, Ghanem KG, Emmanuel P, Zingman BS, Horberg MA, et al. Primary care guidelines for the management of persons infected with HIV: 2013 update by the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis. 2014 Jan. 58 (1):1-10. [Medline]. [Full Text].
Dalla Pria A, Alfa-Wali M, Fox P, Holmes P, Weir J, Francis N, et al. High-resolution anoscopy screening of HIV-positive MSM: longitudinal results from a pilot study. AIDS. 2014 Mar 27. 28 (6):861-7. [Medline].
[Guideline] Geh I, Gollins S, Renehan A, Scholefield J, Goh V, Prezzi D, et al. Association of Coloproctology of Great Britain & Ireland (ACPGBI): Guidelines for the Management of Cancer of the Colon, Rectum and Anus (2017) - Anal Cancer. Colorectal Dis. 2017 Jul. 19 Suppl 1:82-97. [Medline]. [Full Text].
Nigro ND, Vaitkevicius VK, Considine B Jr. Combined therapy for cancer of the anal canal: a preliminary report. 1974. Dis Colon Rectum. 1993 Jul. 36 (7):709-11. [Medline].
Gunderson LL, Winter KA, Ajani JA, Pedersen JE, Moughan J, Benson AB 3rd, 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 Dec 10. 30 (35):4344-51. [Medline].
Peiffert D, Tournier-Rangeard L, Gérard JP, Lemanski C, François E, Giovannini M, et al. 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 Jun 1. 30 (16):1941-8. [Medline].
Haque W, Verma V, Butler EB, Teh BS. Utilization of intensity modulated radiation therapy for anal cancer in the United States. J Gastrointest Oncol. 2018 Jun. 9 (3):466-477. [Medline]. [Full Text].
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 Dec 1. 78 (5):1413-9. [Medline].
Jhaveri J, Rayfield L, Liu Y, Chowdhary M, Tian S, Cassidy RJ, et al. Impact of intensity modulated radiation therapy on survival in anal cancer. J Gastrointest Oncol. 2018 Aug. 9 (4):618-630. [Medline]. [Full Text].
Morris V, Eng C. Metastatic Anal Cancer and Novel Agents. Surg Oncol Clin N Am. 2017 Jan. 26 (1):133-142. [Medline].
Holm T, Ljung A, Häggmark T, Jurell G, Lagergren J. Extended abdominoperineal resection with gluteus maximus flap reconstruction of the pelvic floor for rectal cancer. Br J Surg. 2007 Feb. 94 (2):232-8. [Medline].
Jänes A, Cengiz Y, Israelsson LA. Preventing parastomal hernia with a prosthetic mesh: a 5-year follow-up of a randomized study. World J Surg. 2009 Jan. 33 (1):118-21; discussion 122-3. [Medline].
Serra-Aracil X, Bombardo-Junca J, Moreno-Matias J, Darnell A, Mora-Lopez L, Alcantara-Moral M, et al. Randomized, controlled, prospective trial of the use of a mesh to prevent parastomal hernia. Ann Surg. 2009 Apr. 249 (4):583-7. [Medline].
Brandsma HT, Hansson BM, Aufenacker TJ, van Geldere D, van Lammeren FM, Mahabier C, et al. Prophylactic mesh placement to prevent parastomal hernia, early results of a prospective multicentre randomized trial. Hernia. 2016 Aug. 20 (4):535-41. [Medline].
Prudhomme M, Alline M, Chauvat J, Fabbro-Perray P, Ripoche J, Bertrand MM, et al. Primary prevention of peristomial hernias via parietal prostheses: A randomized, multicentric study (GRECCAR 7 trial). Dig Liver Dis. 2016 Apr 5. [Medline].
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 Oct. 17 (10):2656-62. [Medline].
Hirche C, Dresel S, Krempien R, Hünerbein M. Sentinel node biopsy by indocyanine green retention fluorescence detection for inguinal lymph node staging of anal cancer: preliminary experience. Ann Surg Oncol. 2010 Sep. 17 (9):2357-62. [Medline].
Johnston MJ, Robertson GM, Frizelle FA. Management of late complications of pelvic radiation in the rectum and anus: a review. Dis Colon Rectum. 2003 Feb. 46 (2):247-59. [Medline].
Sheth S, Bleibel W, Thukral C, A-Rahim Y, Beldi G, Csizmadia E, et al. Heightened NTPDase-1/CD39 expression and angiogenesis in radiation proctitis. Purinergic Signal. 2009 Sep. 5 (3):321-6. [Medline].
Lan ML, Yu X, Xiao H, Zhou P, Hu N, Li J, et al. Clinical outcomes and toxicity of postoperative intensity-modulated versus three-dimensional conformal radiation therapy in patients with cervical cancer. Asia Pac J Clin Oncol. 2016 Feb 28. [Medline].
Yoshioka Y, Suzuki O, Nishimura K, Inoue H, Hara T, Yoshida K, et al. Analysis of late toxicity associated with external beam radiation therapy for prostate cancer with uniform setting of classical 4-field 70 Gy in 35 fractions: a survey study by the Osaka Urological Tumor Radiotherapy Study Group. J Radiat Res. 2013 Jan. 54 (1):113-25. [Medline].
Heemsbergen WD, Peeters ST, Koper PC, Hoogeman MS, Lebesque JV. Acute and late gastrointestinal toxicity after radiotherapy in prostate cancer patients: consequential late damage. Int J Radiat Oncol Biol Phys. 2006 Sep 1. 66 (1):3-10. [Medline].
Jahnson S, Westerborn O, Gerdin B. Prognosis of surgically treated radiation-induced damage to the intestine. Eur J Surg Oncol. 1992 Oct. 18 (5):487-93. [Medline].
Kimura T, Iwagaki H, Hizuta A, Nonaka Y, Tanaka N, Orita K. Colorectal cancer after irradiation for cervical cancer--case reports. Anticancer Res. 1995 Mar-Apr. 15 (2):557-8. [Medline].
Markowitz LE, Dunne EF, Saraiya M, Chesson HW, Curtis CR, Gee J, et al. Human papillomavirus vaccination: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2014 Aug 29. 63 (RR-05):1-30. [Medline]. [Full Text].
U.S. Food and Drug Administration. FDA approves expanded use of Gardasil 9 to include individuals 27 through 45 years old. FDA News Release. 2018 Oct 05. Available at https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm622715.htm.
Blaser N, Bertisch B, Kouyos RD, Calmy A, Bucher HC, Cavassini M, et al. Impact of screening and ART on anal cancer incidence in HIV-positive men who have sex with men: mathematical modeling study. AIDS. 2017 May 16. [Medline].
Topical or Ablative Treatment in Preventing Anal Cancer in Patients With HIV and Anal High-Grade Squamous Intraepithelial Lesions: NCT02135419. clinicaltrials.gov. Available at https://clinicaltrials.gov/ct2/show/NCT02135419. June 1, 2018; Accessed: September 25, 2018.
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 Apr. 14 (4):346-53. [Medline].
Christensen AF, Nielsen MB, Svendsen LB, Engelholm SA. Three-dimensional anal endosonography may improve detection of recurrent anal cancer. Dis Colon Rectum. 2006 Oct. 49 (10):1527-32. [Medline].
Nguyen BT, Joon DL, Khoo V, Quong G, Chao M, Wada M, et al. Assessing the impact of FDG-PET in the management of anal cancer. Radiother Oncol. 2008 Jun. 87 (3):376-82. [Medline].
Roach SC, Hulse PA, Moulding FJ, Wilson R, Carrington BM. Magnetic resonance imaging of anal cancer. Clin Radiol. 2005 Oct. 60 (10):1111-9. [Medline].
Long KC, Menon R, Bastawrous A, Billingham R. Screening, Surveillance, and Treatment of Anal Intraepithelial Neoplasia. Clin Colon Rectal Surg. 2016 Mar. 29 (1):57-64. [Medline].
Mahto M, Nathan M, O'Mahony C. More than a decade on: review of the use of imiquimod in lower anogenital intraepithelial neoplasia. Int J STD AIDS. 2010 Jan. 21 (1):8-16. [Medline].
Kim JJ. Targeted human papillomavirus vaccination of men who have sex with men in the USA: a cost-effectiveness modelling analysis. Lancet Infect Dis. 2010 Dec. 10 (12):845-52. [Medline].
Jay N, Berry JM, Hogeboom CJ, Holly EA, Darragh TM, Palefsky JM. Colposcopic appearance of anal squamous intraepithelial lesions: relationship to histopathology. Dis Colon Rectum. 1997 Aug. 40 (8):919-28. [Medline].
Machalek DA, Poynten M, Jin F, Fairley CK, Farnsworth A, Garland SM, et al. Anal human papillomavirus infection and associated neoplastic lesions in men who have sex with men: a systematic review and meta-analysis. Lancet Oncol. 2012 May. 13 (5):487-500. [Medline].
Steele SR, Varma MG, Melton GB, Ross HM, Rafferty JF, Buie WD, et al. Practice parameters for anal squamous neoplasms. Dis Colon Rectum. 2012 Jul. 55 (7):735-49. [Medline].
Markowitz LE, Hariri S, Lin C, Dunne EF, Steinau M, McQuillan G, et al. Reduction in human papillomavirus (HPV) prevalence among young women following HPV vaccine introduction in the United States, National Health and Nutrition Examination Surveys, 2003-2010. J Infect Dis. 2013 Aug 1. 208 (3):385-93. [Medline].
Smyczek P, Singh AE, Romanowski B. Anal intraepithelial neoplasia: review and recommendations for screening and management. Int J STD AIDS. 2013 Nov. 24 (11):843-51. [Medline].
Silvera R, Gaisa MM, Goldstone SE. Random biopsy during high-resolution anoscopy increases diagnosis of anal high-grade squamous intraepithelial lesions. J Acquir Immune Defic Syndr. 2014 Jan 1. 65 (1):65-71. [Medline].
Berry JM, Jay N, Cranston RD, Darragh TM, Holly EA, Welton ML, 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 Mar 1. 134 (5):1147-55. [Medline].
Crawshaw BP, Russ AJ, Stein SL, Reynolds HL, Marderstein EL, Delaney CP, et al. 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 Jan. 58 (1):53-9. [Medline].
PDQ Screening and Prevention Editorial Board. Anal Cancer Prevention (PDQ®): Patient Version. June 1, 2017. [Medline]. [Full Text].

Media Gallery

Anal cancer with typical mass. Courtesy of Luay Ailabouni, MD, FACS, FASCRS.
Paget disease. Courtesy of Luay Ailabouni, MD, FACS, FASCRS.
Anal cancer. Courtesy of Luay Ailabouni, MD, FACS, FASCRS.
Anal cancer in the setting of condyloma (anal warts). Courtesy of Luay Ailabouni, MD, FACS, FASCRS.

of 4

Anal Cancer Workup

Approach Considerations

Screening

Staging

About

Membership

Apps

WebMD Network

Editions

What to Read Next on Medscape

Anal Cancer Workup

Approach Considerations

Screening

Staging

References

Tables

Contributor Information and Disclosures

What would you like to print?

Find Us On

About

Membership

Apps

WebMD Network

Editions

What to Read Next on Medscape

Related Conditions and Diseases

Medscape Consult

News & Perspective

Tools

Slideshow

Most Popular Articles

Recommended