Anal cancer

Anal cancer is a type of cancer which arises from the anus, the distal orifice of the gastrointestinal tract. It is a distinct entity from the more common colorectal cancer. The etiology, risk factors, clinical progression, staging, and treatment are all different. Anal cancer is typically a squamous cell carcinoma that arises near the squamocolumnar junction.

Epidemiology
The American Cancer Society estimates that in 2009 about 5,290 new cases of anal cancer will be diagnosed in the United States (about 3,000 in women and 2,000 in men). It is typically found in adults, average age early 60s.

In the United States, an estimated 710 people died of anal cancer in 2009.

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

Symptoms
Symptoms of anal cancer include bloating and change in bowel habits, a lump near the anus, rectal bleeding, itching or discharge. Women may experience lower back pain due to pressure the tumor exerts on the vagina, and vaginal dryness.

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. In another study done, high-risk types of HPV, notably HPV-16, were detected in 84 percent of anal cancer specimens examined. Based on the study in Denmark and Sweden, Parkin estimated that 90% of Anal cancers are attributable to HPV.
 * Sexual activity: Having multiple sex partners due to the increased risk of exposure to the HPV virus. Receptive anal intercourse, whether male or female, increases the chances of anal cancer sevenfold due to Human papillomavirus. Those who engage in anal intercourse with multiple partners are 17 times more likely to develop anal cancer than those who don't, if their insertive partners are infected with the HPV virus.
 * Smoking: Current smokers are several times more likely to develop anal cancer compared with nonsmokers. 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's 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.


 * Immunosuppression, which is often associated with HIV infection.
 * Benign anal lesions (inflammatory bowel disease (IBD), hemorrhoids, fistulae or cicatrices). Inflammation resulting from benign anal lesions, such as hemorrhoids and anal fistulas, has been considered to cause a predisposition to anal cancer.

Prevention
Since many, if not most, anal cancers derive from human papillomavirus 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, scientists surmise that HPV vaccination may reduce the incidence of anal cancer.

At 22 December 2010, FDA has 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.

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.

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. (Goldstone, SE, Kawalek, AZ, Huyett, JW "Infrared Photocoagulator: A useful tool for treating anal squamous intraepithelial lesions".  2005.  Diseases of the Colon & Rectum 58(5), 1042-1053.

Anal cancer is most effectively 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 anal sphincter, with concomitant fecal incontinence. For this reason, many patients with anal cancer have required permanent colostomies.

In more recent years, physicians have employed a combination strategy including chemotherapy and radiation treatments to reduce the necessity of debilitating surgery. 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 active in anal cancer includes cisplatin and 5-FU. Mitomycin has also been used, but is associated with increased toxicity.

Metastatic or recurrent disease
Up to 10% of patients treated for anal cancer will develop distant metastatic disease. 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.

Prognosis
Based on series of 270 patients, the five year survival by stage was:
 * T1 – 86 percent
 * T2 – 86 percent
 * T3 – 60 percent
 * T4 – 45 percent
 * N0 – 76 percent
 * Node-positive – 54 percent