All About Anal Cancer
What is the anus?
The anus is the opening at the end of the digestive tract, below the rectum. It is where the end of the intestines connect to the outside of the body, and where stool (bowel movements) exit the body.
The rectum is made up of two sections:
- The anal canal- Lies between the anal sphincter (one of the muscles that controls bowel movements) just below the rectum. The anal canal is 3-4 centimeters long.
- The anus (or anal verge)- The transition point between the digestive tract and the skin on the outside of the body.
Muscles within the anal canal and anus control the passage of stool from the rectum to outside the body.
What is anal cancer?
Anal cancer occurs when cells in the lining of the anal canal or anal verge grow uncontrollably and form tumors that can invade normal tissues and spread to other parts of the body.
In the United States, 80% of anal cancers are squamous cell cancers, resembling the cells found in the anal canal. However, this is not true in other parts of the world. In Japan, 80% of anal cancers are adenocarcinomas, resembling the glandular cells seen in the rectum. Cancers of the anal verge may be referred to as "perianal skin cancers," because they usually behave more like skin cancers than like anal cancers. Perianal skin cancers represent about 25% of all anal cancers. Other types of cancer, such as melanoma, Kaposi's sarcoma, and lymphoma, may also develop in the anus.
Anal cancers often begin as anal dysplasia. Anal dysplasia is sometimes referred to as anal intraepithelial neoplasia (AIN), or a "pre-cancer." Anal dysplasia occurs when cells of the anus have abnormal changes but do not show evidence of spreading into the surrounding tissue. The most severe form of anal dysplasia is called carcinoma in situ. This occurs when cells have become cancerous, but have not yet begun to invade normal tissue. Over time, anal dysplasia changes to the point that cells become invasive and are able metastasize (spread to other parts of the body). When anal cancer does spread, it most commonly spreads through direct invasion into nearby tissue or through the lymphatic system. Spread of anal cancer through the blood is less common, but can occur.
What causes anal cancer and am I at risk?
Every year in the United States, there will be about 8,590 cases of anal cancer diagnosed. The incidence of anal cancers has been increasing over the past 30 years. The vast majority (85%) of cases are in Caucasians. The incidence of anal cancer increases with age: patients with anal cancer have an average (median) age of 62 years. Anal cancers are more common white women and black men.
Several factors have been linked to anal cancer. Infection with the human papilloma virus (HPV) has been shown to be related to anal cancers. HPV has also been associated with several other cancers, including cervical cancer and cancers of the head and neck. HPV can be transmitted from person to person through sexual contact. Individuals with a history of multiple sexual partners, anal receptive intercourse, and genital warts are at an increased risk for HPV infection. It is possible that due to the association between HPV and anal cancer, women with history of cervical cancer are at increased risk of developing anal cancer.
Several other factors have been linked to anal cancer. Patients who smoke are three times more likely to develop anal cancer as those that don't smoke. The risk of anal cancer increases with the number of cigarettes smoked per day and the number of years that a person has been smoking.
Although there appears to be an increased rate of anal cancer in patients who have benign (non-cancerous) anal conditions such as an anal fistula, anal fissures, perianal abscesses, or hemorrhoids, it does not appear that these benign conditions are a cause of anal cancer. It is possible that an undiagnosed anal cancer may actually be causing these conditions, and then is later diagnosed when the benign condition is being treated.
The human immunodeficiency virus (HIV) has also been linked to anal cancers. Individuals infected with HIV are at increased risk for infection with HPV, particularly if their CD4 count is low. HIV/AIDS causes changes to the immune system and the loss of the ability to fight off certain types of infections. The incidence of anal cancer is increased in patients with HIV. This is likely related to the fact that patients with HIV are at an increased risk for infection with HPV as well.
How can I prevent anal cancer?
Anal cancer is an uncommon cancer. The overall risk of developing anal cancer is quite low. Avoiding risk factors for anal cancer will reduce the risk of anal cancer even further. The most important factor in preventing anal cancer is preventing infection with HPV. Vaccinations to prevent HPV are available. HPV vaccination is recommended for all boys and girls and is usually given between the ages of 11-12. Recently the FDA expanded its HPV recommendation guidelines to include all adults ages 27-45. Vaccination against HPV could reduce the incidences of anal cancer in both men and women. It is important to talk with your healthcare provider about receiving the HPV vaccine.
Avoiding smoking and unsafe sexual practices can reduce the risk of anal cancer. This is because the immune system in people who smoke is less able to clear the HPV virus than those who do not smoke. In patients who are known to have anal dysplasia, careful monitoring can lead to early detection of anal cancer, and a higher rate of cure with treatment. Removal of areas of anal dysplasia is usually unsuccessful. The rate of recurrence of anal dysplasia after surgical or laser removal is very high. This is likely due to the fact that even if areas of dysplasia are removed, the patient remains infected with HPV, which can cause the development of additional areas of anal dysplasia.
What are the signs of anal cancer?
The most common initial symptom of anal cancer is rectal bleeding. This occurs in about half of patients with new anal cancers. Pain or sensation of an anal mass is seen in about 30% of patients with new anal cancers. Other symptoms include:
- Anal itching.
- Anal discharge.
- Change in bowel patterns.
- Tenderness with palpation.
In some patients, these symptoms may be associated with the presence of warts in the anal region. In general, these symptoms are vague and non-specific. As a result, in one-half to two-thirds of patients with anal cancer, a delay of up to 6 months occurs between the time when symptoms start and when a diagnosis is made.
Rarely, in advanced cases, anal cancers can disrupt the function of the anal muscles. This can result in the loss of control of bowel movements.
How is anal cancer diagnosed?
When anal cancer is suspected, the provider should perform a thorough history and physical examination. The physical exam should consist of a digital rectal examination (DRE) as well as looking at the anal canal using an anoscope (a long, thin instrument that is inserted into the anus to allow the provider to see the inside of the anus and rectum). Anal cancer can only be diagnosed with a biopsy. To perform a biopsy, the provider 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. This bleeding can last for a few days after the procedure. The tissue is then sent to a pathologist who looks at the tissue under 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 starting treatment for anal cancer.
How is anal cancer staged?
Once a diagnosis of anal cancer is made, additional tests will be ordered to determine the extent of the disease. A CT (CAT) scan or MRI scan of the abdomen (belly) and pelvis should be performed to look for enlarged lymph nodes, which can result from spread of the cancer. The CT/MRI can also look at the liver for metastatic disease (cancer that has spread). A PET/CT may also be done. This test can check the extent of disease, including the lymph nodes, and can find any distant metastases. In some cases, an ultrasound of the tumor may be done. The ultrasound uses a probe inserted into the anus to determine the amount of invasion of the tumor into the surrounding tissues. Women with advanced tumors should also have a pelvic exam to see if the tumor has invaded into the vagina.
Anal cancer is most commonly staged using the “TNM system.” The TNM system is used to describe many types of cancers. It has three components: T-describing the extent of the "primary" tumor (the tumor in the anus itself); N-describing if there is cancer in the lymph nodes; M-describing the spread to other organs (metastases). The staging system is very complex. The entire staging system is outlined at the end of this article. Though complicated, the staging system helps healthcare providers determine the extent of the cancer, and in turn, make treatment decisions for a patient's cancer. The stage of cancer, or extent of disease, is based on information gathered through the various tests done as the diagnosis and work-up of the cancer is being performed.
How is anal cancer treated?
Radiation therapy has become the primary treatment of anal squamous cell cancer. The radiation comes in the form of high energy x-rays that are delivered to the patient only in specific areas where the cancer is present. These x-rays are similar to those used for diagnostic x-rays, but they are of a much higher energy. The high energy of x-rays in radiation therapy causes damage to the DNA of cells. Cancer cells divide faster than healthy cells, thus their DNA is more likely to be damaged than that of normal cells. Also, cancer cells are generally less able to repair damaged DNA than normal cells. Cancer cells are killed more easily by radiation than normal cells are. Radiation therapy uses this difference in cells to treat cancers by killing cancer cells, while killing fewer cells in normal, healthy tissue.
Typically, radiation for anal cancer is given 5 days a week, 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. It only affects 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.
Radiation treatment for anal cancer can cause irritation to the skin. This reaction can be quite severe. The skin may become red and dry or may break down. Many patients 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. Increasingly, a technique of radiation delivery called IMRT is being used in an attempt to decrease skin and gastrointestinal effects, as well as decrease the need for treatment breaks.
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."
The most common chemotherapies used are fluorouracil (5FU)/capecitabine and mitomycin C. Sometimes, mitomycin C may be replaced with cisplatin in order to reduce toxic effects from chemotherapy. Two immune targeted therapies are also approved for anal cancer treatment: nivolumab and pembrolizumab. Exactly which chemotherapeutic medications are given for anal cancer varies according to the provider’s preference as well as the patient’s health status and potential side effects. It is important to discuss the risk of each of these medications with your medical oncologist.
If the cancer has spread to distant parts of the body, chemotherapy drugs such as cisplatin, carboplatin, oxaliplatin, leucovorin, paclitaxel 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 chemotherapy are used with radiation, 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.
In the past, surgery was often used to treat anal cancer. The most common surgery done is an abdominal perineal resection (APR). An APR consists of a wide excision (cut) of the anus, including the anal muscles, with placement of a permanent colostomy. A colostomy is done 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 for squamous cell carcinoma results 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, and avoiding the need for permanent colostomy. In contrast, for adenocarcinomas of the anus, surgery is still recommended after chemoradiation.
There are several situations in which surgery should be considered first 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 good while giving the patient the opportunity to 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 for 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.
Clinical trials are extremely important in furthering our knowledge of this disease. It is though clinical trials that we know what we do today, and many exciting new therapies are currently being tested. Talk to your healthcare provider about participating in clinical trials in your area. You can also explore currently open clinical trials using the OncoLink Clinical Trials Matching Service.
Follow-Up Care and Survivorship
After treatment for anal cancer, patients are usually followed every 3-6 months for five years with digital rectal exam and lymph node palpation. They should have an anoscopic examination every 6-12 months for 3 years. It is recommended patients who had locally advanced or node positive disease at diagnosis also have annual chest, abdominal and pelvic CT scans for 3 years.
Anal cancers can take some time to respond to treatment and often continue to shrink months after chemotherapy and radiation have ended. Therefore, it is not unusual to have a residual mass immediately after treatment. The presence of a residual mass does not mean that the treatment did not work. Overall, the chance of long-term cure of anal cancer depends on the extent of the disease at the time it was first diagnosed. Patients with smaller disease without lymph node involvement or distant metastases have a better chance at long-term tumor control than those with larger disease or with lymph node involvement or distant metastases. If anal cancers do recur, they usually do so within the first 2 years after treatment, although recurrences after 2 years can occur. In general, the further out from treatment a patient is without evidence of a recurrence, the better the chances that the cancer will never come back.
The treatment of anal cancer should be a cooperative effort among the patient, the radiation oncologist, the medical oncologist, and the surgeon. It is important that all patients with anal cancer know about their disease so that they can make an informed decision about their treatment.
Fear of recurrence, relationships and sexual health, financial impact of cancer treatment, employment issues, and coping strategies are common emotional and practical issues experienced by anal cancer survivors. Your healthcare team can identify resources for support and management of these challenges faced during and after cancer.
Cancer survivorship is a relatively new focus of oncology care. With almost 17 million cancer survivors in the US alone, there is a need to help patients transition from active treatment to survivorship. What happens next, how do you get back to normal, what should you know and do to live healthy going forward? A survivorship care plan can be a first step in educating yourself about navigating life after cancer and helping you communicate knowledgeably with your healthcare providers. Create a survivorship care plan today on OncoLink.
Resources for More Information
Facts about HPV – McGill University
Appendix: Complete AJCC TNM Staging (2017)
Primary tumor not assessed
No evidence of primary tumor
Carcinoma in situ (Bowen’s disease, high-grade squamous intraepithelial lesion (HSIL), anal intraepithelial neoplasia II–III (AIN II–III)
Tumor 2 cm or less in greatest dimension
Tumor more than 2 cm but not more than 5 cm in greatest dimension
Tumor more than 5 cm in greatest dimension
Tumor of any size invading adjacent organ(s), such as vagina, urethra, or bladder
Regional lymph nodes cannot be assessed
No regional lymph node metastasis
Metastasis to the inguinal (groin), perirectal (around the rectum), internal iliac (pelvic) or external iliac nodes.
Metastasis to the inguinal (groin), perirectal (around the rectum), or internal iliac (pelvic) lymph nodes on the same side of the body.
Metastasis to external iliac (pelvic) lymph nodes
Metastasis to the inguinal (groin), perirectal (around the rectum), or internal iliac (pelvic) lymph nodes, and to the external iliac nodes
M (Distant Metastasis)
Distant metastasis cannot be evaluated.
No distant metastasis.
Distant metastasis, microscopically confirmed
N2 or N3
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