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Anal Cancer

Anal Cancer

The National Cancer Institute predicts that in 2013 7,060 people will be diagnosed with anal cancer in the United States. This is a significant increase from the 5,820 people (3,680 women and 2,140 men) diagnosed in 2011. In the United Kingdom, about 1,100 people are diagnosed with anal cancer each year. Anal cancer is increasing in its incidence and is affecting more people across the world every year. Yet, for many people, anal cancer is difficult to discuss. The social stigma that anal cancer carries with it prevents fair and equitable conversation, awareness, and funding that could support research and care for people with the disease.

95% of anal cancers are caused by the human papillomavirus (HPV). There are many types of HPV. Some HPV types cause benign warts, but some cause lesions (also called dysplasia) that can progress to invasive cancer. HPV-16 and HPV-18 are the high-risk strains responsible for the majority of HPV-associated cancers. Nearly 80% of sexually active people in the United States will have a genital HPV infection at some point in their lives.

HPV causes cervical, anal, vulvar, vaginal, penile and head and neck cancers, as well as recurrent respiratory papillomatosis. Most people fight off HPV infections with the body’s natural defenses. Yet over 30,000 people will be diagnosed with an HPV-related cancer this year in the United States. Researchers do not know why some people get cancer from HPV and others do not. However, some people are at higher risk for developing anal cancer than others.

Intercourse is not necessary to transmit the HPVs that ultimately can cause anal cancer or cervical, vulvar, oral or penile cancers, although it is a common route of transmission. HPV can also be transmitted from person to person by deep kissing, manual stimulation of the genitalia, rubbing, sex toys or multi-site use of any fomite use (i.e. an inanimate object with the potential of being contaminated with a pathogen such as HPV). A person can also spread an HPV infection from one site on his/her own body to another site (e.g. hand-to-genitalia).

The average anal cancer patient in the United States is a woman in her early 60’s with a remote history of atypical Pap smears likely attributed to HPV. Women with a history of high-grade (advanced) cervical or vulvar pre-cancererous lesions (dysplasia) are at an increased risk for anal cancer. After treatment for cervical or vulvar precancerous or cancerous dysplasia, women often return to having normal pap smears. While many women resolve the virus through treatment or naturally through the body’s immune system, for others this same HPV infection may remain undetected for years while it slowly develops into cancer in another site.

According to the University of Hawaii HPV Cohort Study, a cervical HPV infection increases the risk of anal HPV infection by over 20 times. Anal HPV infections also increase the likelihood of cervical HPV infections, but by less (8.5 times). In a presentation of this study at the HPV2010 conference in Montreal, the researchers noted that the majority of cervix-to-anus transmission events happened in the absence of anal intercourse. Women with advanced cervical or vulvar pre-cancer or cancer therefore have an increased risk of anal cancer.

HIV-positive women and men are at a higher risk of developing anal cancer, as HIV weakens the body’s immune system and prevents the healthy resolution of HPV infection. Organ transplant recipients, and people taking medications for autoimmune disorders, often are immunocompromised and also are at higher risk for developing anal cancer.

HIV-positive men with a history of anal intercourse are at the greatest risk for developing anal cancer, although HIV-negative men with a history of receptive anal intercourse are also at high risk compared with the general population. Men who have sex with men (MSM) who do not have HIV are 17 times more likely to develop anal cancer than the general population. The incidence rate doubles for HIV-positive MSM compared with HIV-negative MSM.

Whether male or female, having multiple sexual partners increases the chances of contracting HPV, although having just one sex partner who is infected with HPV can result in an infection that can lead to cancer. While anal intercourse is a well-recognized risk factor for anal HPV infections and anal precancerous dysplasia, shedding (transmission) from elsewhere in the genital tract, other forms of contact (such as touching or multiple-site fomite contact) can be responsible for the transmission of the virus to the anus. In short, anal intercourse is not a pre-requisite for getting anal cancer.

The social stigma associated with anal cancer, however, is in part a direct consequence of this common misconception.While less common, anal HPV infections are also present in healthy, heterosexual men. For example, a 2008 University of Arizona study showed that 16.6% of asymptomatic heterosexual men tested positive for anal HPV on their anus, a third of which were cancer-causing. This highlights that HPV is nearly an unavoidable infection in sexual active people and can easily infect the entire anogenital region.

Every year people who do not have any of the above risk factors also are diagnosed with anal precancer and cancer. This is a simple consequence of the fact that the HPVs that cause this cancer are so ubiquitous in the human population.

While cervical cancer rates have fallen dramatically in the past three decades, HPV-associated cancers in other sites remain on the rise. Cervical cancer has decreased significantly in the United States primarily due to improved early detection of, and treatment for, precancerous lesions (dysplasia). The incidence of anal and oral cancers, however, continues to increase across the U.S. population. One reason is that the medical community has yet to agree to routinely perform optimal early screening and treatment protocols for these sites. While there is no easy procedure to check for HPV-associated oral precancer and cancer, there are numerous tools to check for precancer and cancer in the anus. Widespread practice of effective protocols for early detection and early intervention of HPV-caused anal disease could prevent many individuals from ever developing this cancer, just like it has for cervical cancer.

Anal cancer is often missed or misdiagnosed, many times as hemorrhoids. According to University of California San Francisco’s anal cancer website, the possibility of cancer is often overlooked and symptomatic patients are told that they are suffering from hemorrhoids and are not examined with a simple digital anorectal exam (DARE).

A DARE is when a health professional manually examines one’s anus and rectum. If you are experiencing symptoms such as lumps near the anus, anal bleeding, anal discharges, or changes in bowel movements, you should inform your health care provider, especially if you are at higher risk for anal cancer. Sometimes patients are embarrassed and do not let their providers know they are having symptoms. In patients with anal cancer but with no symptoms, something abnormal may still be felt with a DRE/DAE. If a mass, a thickening, an area of hardness, a lump, an area of localized tenderness or an ulcer is found, then the patient must be referred to clinicians experienced in managing anorectal problems who can evaluate and biopsy the suspicious areas.

If you are diagnosed with what is believed to be a hemorrhoid and it has not resolved for several weeks despite all recommended treatments, please discuss it with your physician and have it formally reevaluated again. Ask whether a DRE/DAE is appropriate. If you have anal cancer, this may help to prevent misdiagnosis as a hemorrhoid and obtain appropriate treatment faster.

For people who are at-risk for anal cancer, in addition to regular DREs/DAEs, it is recommended to have an anal pap smear (also called anal cytology) or high-resolution anoscopy (HRA), where available. An anal pap smear is identical to the technology used for cervical pap smears. HRA is a procedure using a high- resolution magnifying instrument called an anoscope to identify abnormal cells. A list of providers can be found here. Patients can also check with their local gastroenterologist to get information about HRA providers in their area.

In the United States, about 80% of anal cancers are squamous cell carcinomas. Squamous cell carcinoma of the anus is the development of cancer in the squamous, or skin layers. Invasive squamous cell carcimonas of the anus have spread beyond the skin surface to deeper layers of the lining in the anal margin or anal canal. Squamous cell carcinomas of the anus are often treated similarly to squamous cell carcinomas in other parts of the body.

Adenocarcinoma of the anus is the second most common type of anal cancer and develops in glands located under the anal mucosa, which secrete fluids into the anal canal. It often arises from the rectum and is frequently treated as a rectal carcinoma.

Other more rare types of anal cancer include basal cell carcinomas, malignant melanoma, gastrointenstinal stromal tumors, and neuroendocrine tumors. These cancer types are generally not associated with HPV infections are often treated differently.

When detected early, anal cancer is usually curable. The standard of care to treat anal cancer is combined chemoradiation therapy. Doctors reserve surgery for use only if the chemoradiation is not completed or if it is ineffective and leaves residual disease.

Even in early diagnoses, treatment can often have serious and difficult side effects. There are both short term and long term toxicities associated with therapy despite the benefits of cure. Patients who receive local radiation to their pelvis and anus, for example, may suffer from long-term fatigue and gastrointestinal and sexual health dysfunction. For women, this may result in vaginal stenosis, which means narrowing of the vagina due to scar tissue formation, and anal stenosis, often rendering sexual activity extremely painful. For men, it could mean erectile dysfunction and anal stenosis, also rendering sexual activity painful.

Chemotherapy may cause nausea, appetite loss, thinning of the hair, diarrhea, mouth sores, and low blood counts. Sometimes patients require a colostomy (where the colon is diverted and attached to an opening in the abdominal wall) for cure if chemoradiation therapy is ineffective or not feasible. Like many other cancers, mortality rates increase once the disease has spread beyond the origin to other organs (called metastasis). But unlike some other cancers where progress has been made, therapeutic options for those suffering from advanced anal cancer have not improved substantially since the 1980s.

If you are diagnosed with anal cancer, it is important that members of your medical team are familiar with the treatment of anal cancer and have had significant experience. Even if an expert is not available in your area, be sure to ask your physicians many questions, research your disease and get second opinions whenever possible.

Having a team of physicians (medical oncologist, radiation oncologist, and a surgeon) familiar with treatment of cancer of the anal canal/margin is imperative for an optimal treatment response. If your doctor is not experienced with treating this cancer regularly, it may jeopardize your outcome.

The FDA currently recommends the HPV vaccines, Gardasil and Cervarix, for women aged 9-26 to protect against most cases of cervical cancer. Gardasil is also approved for the prevention of HPV-related vulvar and vaginal cancers. The vaccines prevent precancerous lesions caused by HPV types 16 and 18, which are the most common HPV types that cause cancers.  On December 22, 2010, the FDA approved Gardasil for the prevention of anal cancer and precancer in men and women aged 9-26. On October 25, 2011 the CDC recommended the Gardasil vaccine for routine use in males.  In addition to protecting against anal cancer and precancer, Gardasil also prevents most types of genital warts in men and women.

To be most effective, the vaccines should be administered prior to the onset of sexual activity. However, the vaccines still have efficacy after the onset of sexual activity against the HPV types indicated above, although they will not prevent the development of precancerous lesions associated with HPV infections already present at the time of vaccination.

The FDA approved Gardasil’s anal cancer indication based on data that shows that it is safe and effective in preventing anal pre-cancer caused by HPV types 16 and 18. By protecting against an HPV infection, the vaccine prevents the abnormal cells that will eventually develop into cancer.  The FDA expanded Gardasil’s label to protect against anal pre-cancer based on a randomized, controlled trial of men who self-identified as having sex with men. The study is available here.

The HPV and Anal Cancer Foundation testified on November 17, 2010 before the FDA’s Vaccines and Related Biological Products Advisory Committee in support of expanding Gardasil’s indication to include anal cancer. Expanding the cancer indication to men and women for anal cancer is an important step in increasing protection against anal cancer across the population. The Foundation has and will continue to make efforts at the national level to promote increased access to and use of the HPV vaccine to reduce the risk of anal cancer in future generations.

Increasing vaccine inoculation rates is also an essential step in preventing all HPV-caused cancers. Unfortunately, vaccine coverage is currently very poor in the United States compared with several other developed countries. In the United Kingdom, for example, over 88% of adolescent girls have received at least one dose of the vaccine and in Canada, over 60% have. In the United States, just 44% of adolescent girls have received one dose of the vaccine and less than 30% have received all three doses. The benefits of vaccinating adolescent women and men won’t reduce the incidence of anal cancer for years. That, in addition to low vaccination rates in many countries, means that HPV-associated cancer will continue to be a major cause of illness and mortality in the United States and other countries, in the coming years.

To learn more about anal cancer, go to:

American Cancer Society: www.cancer.org/cancer/analcancer/index

Cancer Research UK: http://www.cancerresearchuk.org/cancer-help/type/anal-cancer/

University of California, San Francisco, Department of Medicine: http://id.medicine.ucsf.edu/analcancerinfo/

as well as the resources in Patient Support and Medical Resources.