Anal cancer

Anal cancer is a cancer (malignant tumor) which arises from the anus, the distal opening of the gastrointestinal tract. It is a distinct entity from the more common colorectal cancer.

Anal cancer is typically an anal squamous cell carcinoma that arises near the squamocolumnar junction, often linked to human papillomavirus (HPV) infection. It may be keratinizing (basaloid) or non-keratinizing (cloacogenic). Other types of anal cancer are adenocarcinoma, lymphoma, sarcoma or melanoma. From data collected 2004-2010, the relative five year survival rate in the United States is 65.5%, though individual rates may vary depending upon the stage of cancer at diagnosis and the response to treatment.^[1]

Signs and symptoms

Symptoms of anal cancer can include pain or pressure in the anus or rectum, a change in bowel habits, a lump near the anus, rectal bleeding, itching or discharge. Bleeding may be severe.^[2][3]

Risk factors

• Human papillomavirus: Examination of squamous cell carcinoma tumor tissues from patients in Denmark and Sweden showed a high proportion of anal cancers to be positive for the types of HPV that are also associated with high risk of cervical cancer.^[4] In another study done, high-risk types of HPV, notably HPV-16, were detected in 84 percent of anal cancer specimens examined.^[5] Based on the study in Denmark and Sweden, Parkin estimated that 90% of anal cancers are attributable to HPV.^[6]
• Sexual activity: Having multiple sex partners due to the increased risk of exposure to HPV.^[7][8] Receptive anal intercourse, whether male or female, increases the chances of anal cancer sevenfold due to HPV.^[8] Those who engage in anal intercourse with multiple partners are 17 times more likely to develop anal cancer than those who do not.^[9]
• Smoking: Current smokers are several times more likely to develop anal cancer compared with nonsmokers.^[7] Epidemiologist Janet Daling, Ph.D., a member of Fred Hutchinson's Public Health Sciences Division, and her team found that smoking appears to play a significant role in anal-cancer development that is independent of other behavioral risk factors, such as sexual activity. More than half of the anal-cancer patients studied were current smokers at the time of diagnosis, as compared to a smoking rate of about 23 percent among the controls. "Current smoking is a very important promoter of the disease," said Daling. "There's a fourfold increase in risk if you're a current smoker, regardless of whether you're male or female." They explained that the mechanism behind smoking and anal-cancer development is unknown, but researchers speculate that smoking interferes with a process called apoptosis, or programmed cell death, which helps rid the body of abnormal cells that could turn cancerous. Another possibility is that smoking suppresses the immune system, which can decrease the body's ability to clear persistent infection or abnormal cells.^[8]
• Immunosuppression, which is often associated with HIV infection.^[7]
• Benign anal lesions.^[10][11]
• A history of cervical, vaginal or vulval cancers^[12]
• Cloacogenic. Cloacogenic carcinoma is a rare tumor of the anorectal region originating from a persistent remnant of the cloacal membrane of the embryo. The tumor accounts for 2-3% of anorectal carcinomas and occurs more than twice as often in women.^[13]

Pathology

Most anal cancers are squamous cell carcinomas (epidermoid carcinomas), that arises near the squamocolumnar junction. It may be keratinizing (basaloid) or non-keratinizing (cloacogenic).

Other types of anal cancer are adenocarcinoma, lymphoma, sarcoma or melanoma.

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  Stage 1 anal cancer

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  Stage 2 anal cancer

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  Stage 3 anal cancer

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  Stage 4 anal cancer

• Squamous cell carcinoma of anal rim 01.jpg

  A squamous cell carcinoma of the anus visible grossly

Prevention

Since many, if not most, anal cancers derive from HPV infections, and since the HPV vaccine before exposure to HPV prevents infection by some strains of the virus and has been shown to reduce the incidence of potentially precancerous lesions,^[14] scientists surmise that HPV vaccination may reduce the incidence of anal cancer.^[15]

On 22 December 2010, the U.S. Food and Drug Administration approved Gardasil vaccine to prevent anal cancer and pre-cancerous lesions in males and females aged 9 to 26 years. The vaccine has been used before to help prevent cervical, vulvar, and vaginal cancer, and associated lesions caused by HPV types 6, 11, 16, and 18 in women.^[16]

Screening

Anal Pap smears similar to those used in cervical cancer screening have been studied for early detection of anal cancer in high-risk individuals.^[17] In 2011, the HIV clinic at Jackson Memorial Hospital implemented a program to enhance access to anal cancer screening for HIV-positive men. Nurse practitioners perform anal Papanicolaou screening, and men with abnormal results receive further evaluation with high-resolution anoscopy. The program has helped identify many precancerous growths, allowing them to be safely removed.^[18]

Treatment

Localised disease

Localised disease (carcinoma-in-situ) and the precursor condition, anal intraepithelial neoplasia (anal dysplasia or AIN) can be ablated with minimally invasive methods such as Infrared Photocoagulation.^[19]

Previously, anal cancer was treated with surgery, and in early stage disease (i.e., localised cancer of the anus without metastasis to the inguinal lymph nodes), surgery is often curative. The difficulty with surgery has been the necessity of removing the internal and external anal sphincter, with concomitant fecal incontinence. For this reason, many patients with anal cancer have required permanent colostomies.

Current gold-standard therapy is chemotherapy and radiation treatment to reduce the necessity of debilitating surgery.^[20] This "combined modality" approach has led to the increased preservation of an intact anal sphincter, and therefore improved quality of life after definitive treatment. Survival and cure rates are excellent, and many patients are left with a functional sphincter. Some patients have fecal incontinence after combined chemotherapy and radiation. Biopsies to document disease regression after chemotherapy and radiation were commonly advised, but are not as frequent any longer. Current chemotherapy consists of continuous infusion 5-FU over four days with bolus mitomycin given concurrently with radiation. 5-FU and cisplatin are recommended for metastatic anal cancer.^[21]

Metastatic or recurrent disease

10 to 20% of patients treated for anal cancer will develop distant metastatic disease following treatment.^[22] Metastatic or recurrent anal cancer is difficult to treat, and usually requires chemotherapy. Radiation is also employed to palliate specific locations of disease that may be causing symptoms. Chemotherapy commonly used is similar to other squamous cell epithelial neoplasms, such as platinum analogues, anthracyclines such as doxorubicin, and antimetabolites such as 5-FU and capecitabine. J.D. Hainsworth developed a protocol that includes Taxol and Carboplatinum along with 5-FU. Median survival rates for patients with distant metastases ranges from 8 to 34 months.^[22]

Epidemiology

US

The American Cancer Society estimated that in 2014 about 7,060 new cases of anal cancer would be diagnosed in the United States (4,430 in women and 2,630 in men) .^[23] It is typically found in adults, average age early 60s.^[23]

In the United States, an estimated 800 to 900 people die of anal cancer annually.^[23]

UK

Anal cancer accounts for less than 1% of all cancer cases and deaths in the UK. Around 1,200 people were diagnosed with the disease in 2011, and around 310 people died in 2012.^[24]

Worldwide

Worldwide in 2002 there were an estimated 30,400 new cases of anal cancer.^[6] With approximately equal fractions in the developing (15,900) and developed (14,500) countries.^[6] An estimated 90% (27,400) were attributable to Human papillomavirus (HPV).^[6]

See also

• Genital warts

References

External links

• American Cancer Society – Detailed Guide: Anal Cancer
• Anal Warts, Anal Cancer, and Anal Pap Smears
• Anal Cancer and HPV in Men Who Have Sex With Men
• Clinically reviewed anal cancer information for patients, from Cancer Research UK
• National Cancer Institute (U.S.): Anal Cancer: Information for Health Professionals
• Cancer.Net: Anal Cancer
• The HPV and Anal Cancer Foundation