Anal cancer

For cancer of the colon or rectum, see Colorectal cancer.

(AY-nul KAN-ser)Cancer that forms in tissues of the anus. The anus is the opening of the rectum (last part of the large intestine) to the outside of the body. Anal cancer cases have been increasing over several decades. Infection with human papillomavirus (HPV) is the major risk factor for anal cancer. Explore the links on this page to learn more about anal cancer prevention, treatment, statistics, research, and clinical trials. Squamous cell carcinoma is the most common type of anal cancer.

In the United States, the most common type of anal cancer is squamous cell carcinoma. Studies show that human papillomavirus (HPV) infection is the main cause of this type of anal cancer.

Another type of anal cancer, called anal adenocarcinoma, is very rare.

Risk Factors

Overall, the risk of anal cancer is rising due to increased incidence of human papilloma virus (HPV) infection. Ninety-five percent of anal cancers are HPV related, with the highest risk for serotypes 16 and 18. Involvement of HPV can be pathologically correlated with P16+ staining. Patients with HIV have a higher risk of HPV coinfection, and consequently have a higher risk of anal cancer.

Data suggest that certain sexual practices, such as receptive anal intercourse or a high lifetime number of sexual partners, portend an increased risk of anal cancer. These practices may have led to an increase in the number of individuals at risk of infection with HPV.

Cellular Classification of Anal Cancer

Squamous cell (epidermoid) carcinomas make up the majority of all primary cancers of the anus. Historically, a subset of tumors arising from the epithelial transitional zone were categorized as cloacogenic or basaloid tumors; however, these tumors are now recognized as nonkeratinizing squamous cell cancers and are similarly associated with human papilloma virus.

Lesions in the hair-bearing skin distal to the squamous mucocutaneous junction are defined as perianal cancers. These are typically treated the same as anal canal cancers, although local therapy alone can be considered for discrete skin lesions with significant separation from the anal verge.

Adenocarcinomas starting in anal glands or fistulae formation are rare and generally have clinical features that are similar to rectal adenocarcinoma. (Refer to the Clinical Features section in the PDQ summary on Rectal Cancer Treatment for more information.)

Treatment of anal melanoma is not included in this summary.

Stage Information for Anal Cancer

The anal canal extends from the rectum to the perianal skin and is lined by a mucous membrane that covers the internal sphincter. Tumors of the anal margin (below the anal verge and involving the perianal hair-bearing skin) are classified with skin tumors.

American Joint Committee on Cancer (AJCC) Stage Groupings and TNM Definitions

The following is a staging system for anal canal cancer that has been described by the AJCC and the International Union Against Cancer. The AJCC has designated staging by TNM (tumor, node, metastasis) classification to define anal cancer.

Treatment Option Overview

The optimal approach in patients with advanced disease in still under clinical evaluation.

Stage 0 Anal Cancer Treatment

Standard Treatment Options for Stage 0 Anal Cancer

Stage 0 anal cancer is carcinoma in situ. Rarely diagnosed, it is a very early cancer that has not spread below the limiting membrane of the first layer of anal tissue.

Standard treatment options:

Surgical resection is used to treat lesions of the perianal area not involving the anal sphincter. The surgical approach depends on the location of the lesion in the anal canal.

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

Stages I, II, and III Anal Cancer Treatment

Standard Treatment Options for Stages I, II, and III Anal Cancer

Current sphincter-sparing therapies include wide local excision for small tumors of the perianal skin or anal margin, or definitive chemoradiation therapy (fluorouracil and mitomycin C [MMC]) for cancers of the anal canal. Radical resection is reserved for patients with incomplete responses or recurrent disease.

Continued surveillance with rectal examination every 3 months for the first 2 years and endoscopy with biopsy when indicated after completion of sphincter-preserving therapy is important to monitor for recurrence.

Standard treatment options:

1. Small tumors of the perianal skin or anal margin not involving the anal sphincter may be adequately treated with local resection.
2. The standard of care for all other stage I, II, and III anal cancers in appropriate patients is chemoradiation therapy (external-beam radiation therapy [EBRT] with chemotherapy).
   • Fluorouracil (5-FU) + MMC + radiation therapy.
   • Capecitabine + MMC + radiation therapy.
   • 5-FU + cisplatin + radiation therapy.
3. Alternative strategies such as radiation therapy alone or surgery alone may be considered, depending on the clinical context.
4. Radical resection is reserved for residual or recurrent cancer in the anal canal after nonoperative therapy.

Chemoradiation therapy

Because of historically high rates of recurrence with colostomy alone, chemoradiation therapy is the preferred approach for patients with anal cancer in the absence of distant metastases.

Stage IV Anal Cancer Treatment

Standard Treatment Options for Stage IV Anal Cancer

Standard treatment options:

1. Palliative surgery.
2. Palliative radiation therapy.
3. Palliative chemotherapy (with or without radiation therapy).
   • Cisplatin + infusional fluorouracil (5-FU).
   • Carboplatin + weekly paclitaxel.
   • Docetaxel + cisplatin + 5-FU.
   • Nivolumab.
   • Pembrolizumab.
4. Checkpoint inhibitors.

Advanced-stage therapy

1. In the multicenter randomized phase II International Advanced Anal Cancer InterAACT trial (NCT02560298), published only in abstract form, carboplatin (area under the curve 5) and weekly paclitaxel was compared with standard infusional fluorouracil (5-FU) and bolus cisplatin in patients with advanced-stage anal cancer.
   • With a median follow-up of 25.3 months, the median overall survival (OS) with carboplatin and paclitaxel was improved compared with cisplatin and 5-FU (20 months vs. 12.3 months, hazard ratio [HR] 2.0, P = .014).[Level of evidence: 1iiA]
   • Serious adverse events were more common in patients treated with cisplatin plus 5-FU (62% vs. 36%; P = .016). These promising findings have led international investigators to use carboplatin and paclitaxel as a new backbone in trials for advanced-stage disease, as well as a potential partner for use with radiation therapy. Other chemotherapy regimens, such as modified docetaxel, cisplatin, and 5-FU, are currently under clinical evaluation.
2. The checkpoint inhibitors have also shown activity for patients with metastatic disease. The NCI96773 (NCT02314169) phase II trial of single-agent nivolumab (3 mg/kg every 2 weeks) enrolled 37 patients.
   • The overall response rate was 24%, including two complete responses.
3. The phase Ib KEYNOTE-028 (NCT02054806) trial for patients with advanced tumors with programmed death ligand-1 of at least 1% enrolled a cohort of 24 patients with anal squamous cell carcinoma.
   • The overall response rate was 17%, and an additional stable disease rate was 42%.

Although there is no clear standard of care for patients with metastatic disease, recent studies are uncovering promising new avenues for systemic treatment. Palliation of symptoms from the primary lesion is of major importance. Patients in this stage should be strongly considered for clinical trials.

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

HIV and Anal Cancer

The tolerance of patients with HIV and anal carcinoma to standard fluorouracil and mitomycin C (MMC) chemoradiation therapy is not well defined. In general, patients with HIV are treated similarly to other patients and have similar outcomes, particularly in the era of highly active antiretroviral therapy (HAART). Patients with pretreatment CD4 counts of fewer than 200 cells/μl may have increased acute and late toxic effects. Therefore, patients with a history of AIDS-related complications may have difficulty tolerating a standard regimen, necessitating a dose adjustment or omission of MMC.

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

Recurrent Anal Cancer Treatment

Local recurrences and persistent disease after treatment with radiation therapy and chemotherapy or surgery as the primary treatment may be controlled by using the alternate treatment (surgical resection after radiation and vice versa). Salvage chemoradiation therapy with fluorouracil and cisplatin plus a radiation boost may avoid permanent colostomy in patients with residual tumor after initial nonoperative therapy.[2] Clinical trials are exploring the use of radiation therapy with chemotherapy and radiosensitizers to improve local control.

Preliminary studies in stage IV disease suggest the potential for benefit from alternative chemotherapy regimens (such as carboplatin and paclitaxel in the InterACCT [NCT02560298] trial) or immune checkpoint inhibitors (as in NCI9673 [NCT02314169] and KEYNOTE-028 [NCT02054806]) in this setting.

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

General Information About Anal Cancer

Updated statistics with estimated new cases and deaths for 2021.

Levels of Evidence

Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.

Prognosis

The two major prognostic factors for anal cancer are tumor size (primary tumors <2 cm in size have a better prognosis) and nodal status (refer to the American Joint Committee on Cancer Stage Groupings and TNM Definitions section of this summary for more information).[2] Nodal drainage of the anus follows the inguinal vein. The initial evaluation of a patient with anal cancer will include a careful clinical examination of the inguinal region and biopsy of any palpable lymph nodes.

Anal cancer is usually curable. At presentation, most patients have T1 or T2 disease (≤5 cm), and fewer than 20% of patients have node-positive disease. The 5-year survival for these early-stage patients exceeds 85%. Even in patients with node-positive disease, 5-year survival exceeds 50% in the absence of invasion into adjacent organs or distant metastases.

Anal cancer Resources
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Classification	ICD-10: C21 MeSH: D001005 DiseasesDB: 31467

• American Cancer Society: Anal Cancer
• Anal cancer information from Cancer Research UK
• National Cancer Institute: Anal cancer