Anal Cancer: Risk Factors, Diagnosis, and Management

Edward Fazendin, MD; Alexander Crean, MD; David Stein, MD | February 9, 2016
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Anal cancer is a fairly rare malignancy, accounting for approximately 1-2% of all gastrointestinal
cancers. Approximately 6000 new cases of anal cancer are diagnosed each year, two thirds of
which occur in women. The disease claims about 800 lives per year. The incidence of anal cancer
is rising in the HIV community; however, it has remained fairly stable in the non-HIV
population.[1] The most common cancer of the anus is squamous cell carcinoma (SCC), which
will be the main focus of this presentation.
Image courtesy of David Stein, MD.

This slide depicts the anatomy of the rectum and anus, including major structures and landmarks.
Anal cancer may involve the anal canal, the anal margin (including the perianal skin over a
radius of 5-6 cm from the squamous-mucocutaneous junction), or both.[2]
Image courtesy of Dreamstime / Medscape.

Which of the following is the greatest risk factor for the development of SCC of the anus?
A. Smoking
B. Age >55 years
C. Human papillomavirus (HPV) infection
D. History of colon cancer
Image courtesy of David Stein, MD.

Answer: C. Human papillomavirus (HPV) infection.

Infection with HPV is the single greatest risk factor for the development of anal cancer. Similar
to cervical cancer, HPV infection causes dysplastic changes in the anal/perianal epithelium. This
dysplasia is divided into two categories: low-grade anal intraepithelial neoplasia (LGAIN) and
high-grade anal intraepithelial neoplasia (HGAIN). HGAIN is generally accepted as the direct
precursor lesion to anal SCC. Other risk factors include, but are not limited to, age greater than
55 years, receptive anal intercourse, concomitant sexually transmitted disease (STD),
immunosuppression (as in transplant recipients or individuals with HIV infection), pelvic
irradiation, and smoking.[3-5]
Image courtesy of David Stein, MD.

A 26-year-old HIV-positive patient comes into your office after noticing several small bumps
around the anus. On anorectal examination, you observe several verrucous lesions occurring
circumferentially in the perianal area.
Which of the following is the most appropriate next step in management?
A. Referral to a colorectal surgeon
B. Anal Papanicolaou testing
C. Close observation in the office at regular intervals
D. Colonoscopy
Image courtesy of David Stein, MD.

Answer: A. Referral to a colorectal surgeon.

A focused physical examination, including a digital rectal examination (DRE), is the first step in
the diagnosis of anal cancer. Referral to a colorectal surgeon is the next key step in the
management of patients with anal or perianal lesions. The clinical presentation of anal cancer and
its precursor lesions is highly variable, and this condition is often difficult to detect on physical
examination, especially early in its course. In certain populations, particularly
immunosuppressed patients, Papanicolaou testing may be useful in detecting HPV infection, but
it does not aid in cancer diagnosis. Colonoscopy may be beneficial as a screening tool for
concomitant colon cancer, but it is not the first step in the workup of anal lesions. Besides
palpable lesions, patients may also present with bleeding, itching, discharge, or altered bowel
habits.[3-5]
Image courtesy of Edward Fazendin, MD.

When a patient is referred to a colorectal surgeon for evaluation of anal lesions, the following
two methods are commonly used to obtain a diagnosis:

High-resolution anoscopy

Anoscopy with targeted destruction of lesions

High-resolution anoscopy (shown), similar to colposcopy, uses acetic acid to identify dysplasia
in the perianal area and anal canal. Anoscopy with targeted destruction uses electrocauterization
and excisional biopsy both to remove lesions and to provide tissue for biopsy. The two methods
are equally effective in diagnosing anal cancer or dysplasia, and the choice between them is
based on the individual surgeon's preference.[3]
Image courtesy of Wikimedia Commons.

A 35-year-old HIV-positive patient is found to have perianal lesions positive for SCC on
excisional biopsy. Computed tomography (CT) of the abdomen and pelvis reveals multiple
nodules in the liver that are suspicious for metastasis. Biopsy of these nodules is positive for
SCC.
What is the clinical stage of this patient's anal cancer, according to the staging system formulated
by the American Joint Committee on Cancer (AJCC) and the Union for International Cancer
Control (UICC)?
A. Stage I
B. Stage II
C. Stage III
D. Stage IV
Image courtesy of Wikimedia Commons.

Answer: D. Stage IV.

CT of the abdomen and pelvis is the most useful tool for evaluating distant metastases to solid
organs and lymph nodes, as well local invasion into nearby organs. As with other malignancies,
distant metastases classify anal cancer as stage IV. Stage I and II lesions are determined by tumor
size. Stage III anal cancers all involve spread to lymph nodes or invasion into adjacent organs,
including the bladder, vagina, and uterus. Endoanal ultrasonography (EAUS) is an adjunctive
tool used to assess the depth of invasion of cancers, as well as spread to local lymph nodes.
Positron emission tomography (PET)/CT may also be of use if CT findings are unclear.[1-3]
Table courtesy of Medscape.

A 47-year-old patient is found to have a 2-cm biopsy-proven SCC of the anal canal without
distant metastases or invasion into adjacent organs.
Which of the following is the most appropriate treatment for this patient?
A. Abdominoperineal resection (APR)
B. Chemotherapy with radiation therapy
C. Wide local excision
D. Radiation therapy alone
Image courtesy of David Stein, MD.

Answer: B. Chemotherapy with radiation therapy.

The gold standard for SCC of the anal canal is known as the Nigro protocol. This includes a
combination of external radiation therapy and systemic chemotherapy. The chemotherapeutic
agents used are mitomycin C and 5-fluorouracil (5-FU). The approximate duration of therapy is 4
weeks. The anal canal should be reexamined 4-6 weeks after the completion of therapy. If anal
cancer persists or recurs after treatment according to the Nigro protocol, it can be treated by
means of radical surgical resection (eg, APR). In the case of perianal SCC, wide local excision is
the treatment of choice.[1-3,6]

The Nigro protocol yields 5-year cancer-free rates in the range of 70-90%. Even if anal cancer
does recur after treatment with this protocol, APR is potentially curative. This procedure involves
removal of the anus, the rectum, and a portion of the perineum, as well as creation of a
permanent colostomy. Potential complications of treatment fall into three main categories, as
follows:

Radiation-related - Ulceration, skin damage, anal stenosis

Chemotherapy-related - Nausea, hair loss, lung inflammation

Surgical - Bleeding, infection, damage to normal healthy tissue

There is also a risk of death associated with chemotherapy and surgery.[5]

Image courtesy of David Stein, MD.

The previously mentioned patient with a 2-cm biopsy-proven SCC of the anal canal is
successfully treated with chemotherapy and radiation therapy. (The slide shows EAUS of an
anal-canal cancer.)
At what intervals should this patient subsequently be seen and examined?
A. Every 6 months for the first 5 years
B. Every 3-6 months for the first 2 years, then every 6-12 months for up to 5 years
C. Every 1 month for the first year, then every 6 months for 5 years
D. Yearly for the next 5 years
Image courtesy of David Stein, MD.

Answer: B. Every 3-6 months for the first 2 years, then every 6-12 months for up to 5 years.
After successful treatment with chemotherapy and radiation therapy, patients should be examined
by means of DRE (shown) or anoscopy at regular intervals. It is recommended that these patients
be seen and examined every 3-6 months for the first 2 years, then every 6-12 months for up to 5
years. After this time, patients should be seen on a yearly basis.[3]
Image courtesy of Dreamstime.

Adenocarcinoma accounts for approximately 3-9% of all anal cancers. There are three subtypes
of anal adenocarcinoma, as follows:

Rectal type

Anal gland type

Anorectal fistula type

Rectal-type adenocarcinoma arises from the upper anus and is not distinguishable from
adenocarcinoma of the lower rectum. It is treated according to rectal cancer protocols, with either
local or radical excision performed. APR is the most definitive therapy for rectal-type
adenocarcinoma of the anus.[1,2]
Other cancers of the anus are exceptionally rare. The slide depicts a case of anal leukemia.
Image courtesy of David Stein, MD.

Melanoma is a very rare type of anal cancer, accounting for fewer than 1% of anal malignancies.
Despite the exceeding rarity of melanoma in the anus, the anal canal is the third most common
location for this cancer, after the skin and eyes. A high index of suspicion is required to make the
diagnosis of anal melanoma, which can often masquerade as a deeply pigmented hemorrhoid.
Pathologic diagnosis requires examination under anesthesia and biopsy. Unfortunately, anal
melanoma is difficult to treat and does not respond to the chemotherapy, radiation therapy, or
immunotherapy typically used for other melanomas. The prognosis is poor, and surgical excision
is the only treatment, though it does not offer any survival benefit.[1-3]
Image courtesy of David Stein, MD.

Although anal cancer is a rare malignancy, it is fairly prevalent in certain at-risk populations.
These populations should be screened carefully, with early referrals to colorectal surgeons as
indicated. Anal cancer is treatable, and it is curable if diagnosed early. The gold standard of
treatment is the Nigro protocol, which combines radiation therapy with chemotherapy. Excision
is indicated for perianal and recurrent disease. Close surveillance is required after therapy to
monitor for recurrence. There are several other subtypes of anal cancer that are exceedingly rare
but warrant referral to a colorectal surgeon if suspected.
Image courtesy of David Stein, MD.
http://reference.medscape.com/features/slideshow/anal-cancer#page=17