Anal cancer and anal canal cancer

What is anal cancer?

Anal cancer is a rare malignant tumour which grows in or around the anus. Most anal cancers grow within the mucosa of the anal canal. This lies between the rectum and the anal verge. Other perianal cancers grow on the skin outside of the anal verge.

Most anal cancers are classified as squamous cell carcinoma (SCC). There are two types:

• Keratinising SCC or basaloid SCC — this grows outside the anal canal
• Non-keratinising SCC or cloacogenic SCC — this grows within the anal canal

An anal adenocarcinoma is a rare form of anal cancer. It grows from glandular cells at the junction of the anal canal and the rectum—the transitional zone. Other forms of anal cancer include basal cell carcinoma, lymphoma, sarcoma, mucosal melanoma, and extramammary Paget disease.

Who gets anal squamous cell cancer?

Anal squamous cell cancer occurs in both men and women. It is slightly more common in women than in men, but is rare in both sexes, with an annual incidence of 1 in 100,000 people. It usually arises in adults over the age of 45 years (80% are older than 60 years), but may rarely be diagnosed in young adults.

The risk of anal cancer is greater in the following groups of patients:

• People with anal intraepithelial neoplasia (AIN) — a precursor lesion
• Men and women who have receptive anal intercourse
• Men and women infected with human immunodeficiency virus (HIV). Anal cancer is more common in patients with advanced disease, acquired immune deficiency syndrome (AIDS), when the incidence is 137 in 100,000.
• Men who have had sex with men
• Immunosuppressed patients, for example, organ transplant recipients
• Intravenous drug users
• People with a high lifetime number of sex partners
• Cigarette smokers, who are 4 times more likely than non-smokers to have anal cancer
• People who have injured their anal mucosae, such as anal fistulae in inflammatory bowel disease or anal trauma
• Women, and less often men, with lichen sclerosus
• People with a history of genital warts
• Women with a history of cervical cancer, abnormal cervical smears (CIN), vulval cancer, vulval intraepithelial carcinoma (VIN), or men with penile cancer or penile intraepithelial carcinoma (PIN).

In people that have had more than one type of cancer due to human papillomavirus (HPV) infection, anal cancer can be at the same time, after or before cancers in other genital sites (cervix, vulva, vagina and in males, penis).

Patients with anal cancer (eg, adenocarcinoma) that do not have HPV infection are older than HPV positive patients.

What causes anal cancer?

Nearly all (90%) anal cancers are attributable to persistent infection with HPV, the cause of genital warts. Certain strains of HPV are known to be oncogenic (cancer-causing), especially types HPV 16 and 18, and these two infections cause more than 90% of anal cancers. Rarely, subtyping of HPV has detected low-risk strains such as HPV 6 or multiple strains of HPV associated with anal cancer. The HPV infection is sexually acquired, but it is not necessary to have had anal intercourse for HPV to reach the anal canal. HPV is just as commonly detected in the anus as in the cervix, although anal cancer is not nearly as common as cervical cancer.

In Australia and New Zealand, the rates of anal cancer are increasing in association with documented increases in infection with HPV.

What are the symptoms and signs of anal cancer?

Anal cancer may present with:

• Bleeding from the anus
• A growing lump within or outside the anus
• Anal itching or pain
• A mucus or jelly-like discharge from the anus
• Constipation, bloating, diarrhoea or faecal incontinence (leakage), which can cause incontinence-associated dermatitis.

Symptoms are often thought initially to be due to haemorrhoids (piles), polyps or skin tags.

See images of anal cancer.

How is anal cancer diagnosed?

Anal cancer may be suspected from the appearance of the lesion, which is an irregular nodule on the skin surface or within the anal canal and bleeds easily on contact. It may be detected by digital anal examination, anoscopy (use of a special instrument to inspect the anus), proctoscopy/sigmoidoscopy (inspection of the rectum) or colonoscopy (inspection of the entire colon or large bowel).

High-risk patients (eg those with HIV infection or immunosuppressed after an organ transplant) may be offered anal cytology smears to detect high grade squamous intraepithelial lesions, similar to those used in cervical cancer screening. A swab is inserted into the lower rectum and rolled around the anal canal as it is withdrawn. The swab is processed in the laboratory and examined to detect abnormal cells. Suspicious smears are followed by high-resolution anoscopy.

Skin or mucosal biopsy is then performed to confirm the diagnosis by histopathology.

Imaging is usually undertaken before treatment, to determine the extent of cancer and whether it has spread to local lymph glands or elsewhere in the body. Tests may include:

• Ultrasound scan
• CT scan
• MRI scan
• Chest X-ray
• Blood tests.

How is anal cancer treated?

Anal cancer is usually treated by a combination of:

• Surgical excision of small, external lesions
• Radiotherapy
• Chemotherapy.

Radiotherapy and chemotherapy without surgery preserve the anal sphincter so that the patient can continue to have normal bowel motions with reduced risk of incontinence of faeces.

Abdominoperineal resection with a colostomy is not usually required but may be performed if initial treatment is unsuccessful. The procedure involves excision of anus, rectum and a section of the colon, surgical closure of the rectum and diversion of the colon to open out onto the abdominal wall.

What is the outlook after the treatment of anal cancer?

Cure rates depend on the thickness of the tumour and whether cancer has spread to other sites at the time of diagnosis. Overall, 5-year survival is 60% for males and 70% for females.

Treatment may result in faecal incontinence.

Long-term follow-up may detect the secondary spread of cancer (metastases) to local lymph glands or elsewhere. These are difficult to treat. Further radiation treatment or chemotherapy may be offered.

Can anal cancer be prevented?

HPV vaccination is expected to reduce the incidence of anal cancer in the future. In Australia, boys and girls are offered quadrivalent HPV vaccination (Gardisil™), protecting them against HPV 16, 18, 6 and 11. In New Zealand, 9-valent vaccination is offered to boys and girls up to the age of 26. Vaccination programmes vary in other countries.

Most sexually active men and women will acquire at least one subtype of genital HPV, the majority within the first 5 years of onset of sexual activity. For maximum efficacy, vaccination needs to be undertaken before the onset of sexual activity. HPV infection rates can be reduced by the use of condoms during intercourse and limiting the number of sexual partners.