The Anus

The anus is the part of the large bowel that opens to the outside of the body. It is the tube that your stools pass through as you empty your bowels. You may hear it called the ‘anal canal’. It is about 3 cm long, and is at the end of your rectum. There is more information about the large bowel in our bowel cancer section.

The cells of the anus
The lining of the canal between the outer skin (the perianal area) and the rectum is made up of squamous cells. Most anal cancers are squamous cell cancers.

The area where the anal canal meets the rectum is called the transitional zone. Here the lining of the anus changes and is made up of both squamous and glandular cells. Glandular cells make the mucus that helps stools (faeces) pass through the anus smoothly. Doctors call this area 'the dentate line'. A rare type of anal cancer can develop from these cells, called adenocarcinoma of the anus.

Parts of the anus
The lower part of the anus is called the anal margin. The anal margin contains muscles called the anal sphincters. The external anal sphincter is the muscle you use to control your bowel movements.

Treatment of Anal Cancer

Radiation Therapy
Radiation therapy has become the mainstay of treatment of anal cancer. The radiation comes in the form of high energy x-rays that are delivered to the patient only in the areas at highest risk for cancer. These x-rays are similar to those used for diagnostic x-rays, but they are of a much high energy. The high energy of x-rays in radiation therapy results in damage to the DNA of cells. Cancer cells divide faster than healthy cells, and so their DNA is more likely to be damaged than that of normal cells. Additionally, cancer cells are generally less able to repair damaged DNA than normal cells are, so cancer cells are killed more easily by radiation than normal cells are. Radiation therapy exploits this difference to treat cancers by killing cancer cells, while killing fewer cells in normal, healthy tissue. Typically, radiation for anal cancer is given daily, Monday through Friday, for 5 to 6 weeks. The radiation treatments themselves are short, lasting only a few minutes. Like diagnostic x-rays, radiation treatments cannot be felt and do not hurt. Radiation is delivered like a beam of light, only affecting areas where it is aimed. In treatment of anal cancer, the radiation is usually aimed at the entire pelvis for the first 2-3 weeks so that any cells in the lymph nodes surrounding the anus are treated with radiation. After this, the radiation is aimed more specifically at the anus in the lower part of the pelvis. Most commonly, radiation treatment for anal cancer can result in irritation to the skin. This reaction can be quite severe with redness, dryness, and breakdown of the skin. Often, patients will require a break during radiation treatment to allow the skin to heal prior to resuming treatment. Other side effects of radiation can include fatigue, diarrhea, and lowering of blood counts.

Chemotherapy
Chemotherapy refers to medications that are usually given intravenously or in pill form. Chemotherapy travels throughout the bloodstream and throughout the body to kill cancer cells. This is one of the big advantages of chemotherapy. If cancer cells have broken off from the tumor and are somewhere else inside the body, chemotherapy has the chance killing them, while radiation does not. In the setting of anal cancer, chemotherapy is most commonly given at the same time as radiation. This will be discussed further below under the section entitled "Combined Modality (Chemoradiotherapy)."

A number of different chemotherapeutic agents exist, each with their own side effects. The most common chemotherapies used in anal cancer are 5 flourouracil (5FU) and mitomycin C. Sometimes, mitomycin C may be replaced with cisplatin in order to reduce toxicities from chemotherapy. Exactly which chemotherapeutic agents are given for anal cancer varies according to the physician giving them. It is important to discuss the risk of each of these medications with your medical oncologist. Based on your own health status and the risks of side effects that you are willing to accept, the choice of chemotherapy can vary.

Chemotherapy is used in different situations to treat anal cancer. If the cancer is localized to the anus and pelvic lymph nodes, it may be used in combination with radiation therapy to achieve the best chance of killing all of the cancer cells (see “Combined Modality (Chemoradiotherapy).” If the cancer has spread to distant parts of the body, chemotherapy drugs such as cisplatin, carboplatin, and 5FU may be used without radiation to reduce the number of tumor cells and prevent or minimize symptoms all over the body. This is the case because chemotherapy is able to travel throughout the bloodstream, while radiation is not. In this setting, radiation may be used separately to relieve certain symptoms, such as pain, from cancer in other parts of the body. Unfortunately, if cancer is present in organs distant from the anus, chemotherapy is generally not very successful at controlling it.

Combined Modality (Chemoradiotherapy)
Chemotherapy has been shown to be radiosensitizing when given at the same time as radiation therapy. This means that the effect of the radiation is increased when given together with chemotherapy. Several large trials have shown that local control of the tumor is significantly improved when 5FU and mitomycin with chemotherapy are used, as compared to radiation alone. Using chemotherapy and radiation together has not been shown to change the rate of survival of patients when compared to radiation alone; however, using chemotherapy and radiation together has been shown to reduce the risk of cancer recurring (coming back) in the anus. For this reason, combined modality treatment is recommended for most patients with anal cancer, unless a certain patient is unable to tolerate chemotherapy and radiation together. If this is the case, the patient may have radiation with or without chemotherapy given at a separate time.

Surgery
Although surgery was the primary treatment for anal cancer 20 years ago, its role has greatly diminished since then. When performed, surgical resection usually is an abdominal perineal resection (APR), which consists of a wide excision of the anus, including the anal muscles, with placement of a permanent colostomy. A colostomy is performed by connecting the bowel to a hole in the abdominal wall (called a stoma). The stool that passes through the stoma is collected in a bag that is attached to the outside of the abdominal wall with adhesive. This bag can then be emptied by the patient as needed. Because the combination of chemotherapy and radiation therapy result in similar rates of local control and survival when compared to surgery, chemoradiation has been favored over surgery because it offers patients a good chance at preserving anal sphincter function, avoiding the need for permanent colostomy.

There are several situations in which surgery should be considered for anal cancer. Patients with carcinoma in situ or small, well-differentiated anal cancers that have not invaded into the anal sphincter can sometimes undergo a surgical excision without removing the anal muscles. In these early cases, the results of surgical excision can be quite good, and the patient can avoid the potential side effects of chemoradiotherapy. Alternatively, extensive anal cancers that have destroyed the anal sphincter, such that the patient cannot control bowel movements, are often treated with surgery (an APR). In these cases, patients have already lost their sphincter function, and require a colostomy to handle bowel movements. Because patients in this situation usually have very large tumors, they may require surgical removal of the tumor, which will usually be followed by radiation, with or without chemotherapy, after the operation. Surgery can also be performed in patients who cannot otherwise tolerate radiation therapy, or who do not want radiation therapy Finally, surgery is often performed if cancer recurs in the anus following previous treatment with radiation therapy if additional chemotherapy and radiation cannot be given.

Stages of Anal Cancer

Once a diagnosis of anal cancer is made, additional test should be ordered to determine the extent of the disease. A CT (CAT) scan or MRI of the abdomen and pelvis should be performed to look for abnormally enlarged lymph nodes, which can result from spread of the cancer, and to examine the liver for metastatic disease. A chest x-ray is often performed to look for spread of the cancer to the lungs. In some cases, an ultrasound of the tumor using a probe that is inserted into the anus can be used to determine the amount of invasion of the tumor into the surrounding tissues.

Anal cancer is most commonly staged using the TNM staging system which is determined by the American Joint Committee on Cancer. The "T stage" represents the extent of the primary tumor itself. The "N stage" represents the degree of involvement of the lymph nodes. The "M stage" represents whether or not there is spread of the cancer to distant parts of the body. These are scored as follows:

T Stage
Tis: Carcinoma in situ
T0: No evidence of primary tumor
T1: Tumor 2 cm or less in greatest dimension
T2: Tumor is greater than2 cm but less than 5 cm in greatest dimension
T3: Tumor is greater than5 cm in greatest dimension
T4: Tumor of any size that invades adjacent organs including the vagina, urethra, or bladder. Tumors that invade the anal sphincter only do not qualify as T4 tumors

N Stage
N0: No evidence of spread to the lymph node
N1: Spread of cancer to the lymph nodes directly adjacent to the rectum (perirectal lymph nodes)
N2: Spread of the cancer to lymph nodes of the inguinal or internal iliac lymph node chains on one side only.
N3: Spread of the cancer to lymph nodes of the inguinal or internal iliac lymph node chains on both sides OR cancer involvement of both the perirectal lymph nodes and the inguinal lymph nodes

M Stage
M0: No evidence of distant spread of the cancer
M1: Evidence of distant spread of the cancer to other organs, or to lymph node chains other than the ones lists under "N stage"

The stage of the cancer is reported by stating the stage of the T, the N, and the M. For example, a patient with a 4 cm tumor that had spread to perirectal lymph nodes, but did not invade into adjacent organs or spread to any other lymph nodes would be classified as T2N1M0. The staging can be further condensed into a stage group, which takes the various combinations of TNM and places them into groups designated stage 0-IV. While there is a system for stage grouping of anal cancers, these tumors are more commonly referred to by their direct TNM stage.

Although this system of cancer staging is quite complicated, it is designed to help physicians describe the extent of the cancer, and therefore, helps to direct what type of treatment is given.

Diagnose of Anal Cancer

When anal cancer is suspected, the physician should perform a thorough history and physical examination. The physical exam should consist of a digital rectal examination (DRE) as well as visualization of the anal canal using an anoscope or bronchoscope (a long, thin instrument that is inserted into the anus to allow the physician to see the inside of the anus and rectum).

Ultimately, anal cancer can only be diagnosed with a biopsy. To perform a biopsy, the physician uses a needle or a small pair of scissors or clamps to remove a piece of the tumor. It is common for there to be some mild bleeding after a biopsy is taken, and this bleeding can last for a few days after the procedure. The tissue is then sent to a pathologist who looks at the tissue underneath a microscope to determine whether the tumor is cancerous or not. Because a number of benign tumors and lesions can resemble anal cancer on physical examination, a biopsy should always be performed before initiating treatment for anal cancer.

Types of Anal Cancer

The anus is made up of different types of cells. This is because it lies both inside and outside the body. The types of anal cancer depend on the type of cell the cancer has grown from. They are

• Squamous cell cancer
• Non epidermoid cancers
• Adenocarcinoma
• Basal cell carcinoma
• Melanoma

Squamous cell cancer

About 9 out of 10 (90%) anal cancers are squamous cell cancers, sometimes called epidermoid cancers. There are 3 types of squamous cell anal cancer

• Large cell keratinising
• Large cell non keratinising (also called transitional)
• Basaloid

Non keratinising and basaloid cancers are sometimes grouped together as ‘cloacogenic’ anal cancer. A keratinising cancer has keratin (the protein that forms your hair and nails) in the cancer cells. This type of anal cancer starts in the transitional zone of the anal canal, where the squamous cells meet the glandular cells. All the squamous cell types of anal cancer are treated in the same way.

Non epidermoid cancer

The other 1 out of 10 anal cancers (10%) are adenocarcinoma, small cell cancers, 'undifferentiated' cancers (known as basaloid cancers) and melanomas. This group is known as non-epidermoid cancers. They behave differently to squamous cell anal cancers, so the treatment is different.

Cancers that start at the anal margin, usually look more like normal cells (they are 'well differentiated'). Anal margin tumours are more common in men than women. Cancers that start higher up in the anal canal are more common in women.

Adenocarcinoma

This is a rare type of anal cancer that affects the glandular cells that produce mucus in the anal canal. Only 5% of anal cancers are this type. This type of anal cancer is treated in the same way as rectal cancer.

Basal cell carcinoma

This is a type of skin cancer and it develops in the area around the anus. You can find information about treatment of basal cell cancers in the skin cancer section of CancerHelp UK.

Melanoma

This is another type of skin cancer. These cancers develop from the cells that produce melanin, the pigment or colour for the skin. Treatment is the same as for other melanomas.

Symptoms of Anal Cancer

The symptoms can be similar to other problems of the anus, such as piles or anal fissures.

The most common symptom is bleeding from the back passage (rectal bleeding). Nearly half of all people diagnosed with anal cancer have had rectal bleeding or blood in their stools. Other cancer symptoms can include

• Small lumps around the anus, which may be confused with piles (haemorrhoids)
• Pain in the anal area – 1 in 3 people (30%) have some pain in the area or a sensation of a lump there
• Discharge of mucus from your back passage Difficulty in controlling your bowels (faecal incontinence)
• A lump (or lumps) in the groin

But 1 in 5 people (20%) diagnosed with anal cancer don’t have any of these symptoms.

Remember – anal cancer is rare, so if you have any of these symptoms it is more likely to be something else. But it is still important to report them to your doctor.

Risks and Causes of Anal Cancer

How common anal cancer is
Anal cancer is a rare cancer. About 850 people are diagnosed in the UK each year. It is slightly more common in women than men, with rates increasing in women over the past 10 years. There are several risk factors which causes anal cancer.

What risk factors are
Anything that increases your risk of getting a disease is a risk factor. Different cancers have different risk factors. Even if you have more than one risk factor it doesn’t mean you will definitely get the disease. And just because researchers investigate a possible cause, that doesn't mean it will turn out to be a risk factor.

Human papilloma virus (HPV)
There are over 100 different types of human papilloma virus (HPVs). Some types are called the ‘wart virus’ or ‘genital wart virus’ as they cause genital warts. Some types of HPV are passed on from one person to another through sexual contact.

Up to 8 out of 10 people (80%) in the UK are infected with the HPV virus at some time during their lifetime. For many people, the virus causes no harm and goes away without treatment.

Over 8 out of 10 (80%) people who are diagnosed with anal cancer have evidence of HPV infection in the anal area. Of the different types of HPV, types 16 and 18 are the most commonly found in anal cancer. Invasive anal cancer is thought to develop from the growth of abnormal cells (squamous intraepithelial lesions) caused by HPV infection.

If you have a history of genital warts (which are caused by the HPV virus) you have an increased risk of anal cancer. The risk is higher again if you have had anal warts.

Sexual activity
There is some evidence that that the more sexual partners you have had, the more likely you are to develop anal cancer. This may be because more partners means more chances of contact with the HPV virus. Also, women who have anal intercourse, and men who have receptive anal intercourse have a higher risk of developing anal cancer. This may be because they are more likely to have HPV infection of the anus, or it might be due to other factors, such as inflammation of the anus.

Other sexually transmitted infections
Some studies have shown that other sexually transmitted infections, including the herpes virus, syphilis and gonorrhoea, are associated with an increased risk of anal cancer. This is probably because people who have had other sexually transmitted infections are more likely to have also picked up HPV.

History of cervical or vaginal cancer
If you have had cervical or vaginal cancer your risk of developing abnormal cells in the anus or anal cancer is higher. Risk is also slightly increased for women with a history of abnormal cells in the cervix (cervical intraepithelial neoplasia). This is probably because of risk factors common to cervical and anal cancers, such as HPV infection and smoking.

Smoking
Smoking has also been shown to increase the risk of cancer of the anus. Giving up smoking can reduce your risk of developing many cancers, including anal cancer.

Lowered immunity
If you have lowered immunity you are at greater risk of developing anal cancer. Compared to the general population, you have an increased risk if you have HIV or are taking medicines to damp down your immune system after an organ transplant (for example, a kidney transplant). The risk of anal cancer related to HIV infection is especially high in younger adults.

Age
Your risk of developing anal cancer increases as you get older. But the risk is still small as anal cancer is a rare cancer.