Anal cancer accounts for about 2 percent of gastrointestinal cancers reported annually in the United States. It is estimated that approximately 3,400 new cases will be diagnosed in 2000. Recent epidemiologic and virologic studies have determined that most cases of anal carcinoma are caused by human papillomavirus (HPV) infection. There is little evidence to suggest an association with hemorrhoids, fissures, fistulae or inflammatory bowel disease. Ryan and colleagues recently reviewed the clinical and epidemiologic features of this malignancy along with current management strategies.
Most of the anal canal is lined by squamous mucosa. Tumors that arise distally below the dentate line are typically keratinizing squamous cell cancers. These are viewed as skin cancers and treated by local excision. Cancers above the dentate line are of squamous mucosal origin and may consist of large-cell or small-cell tumors. Lymphatic drainage of anal cancers above the dentate line is by the perirectal and paravertebral nodes; the inguinal and femoral nodes drain those occurring below. Patients with unexplained inguinal adenopathy should always undergo close examination of the rectal area and the anal canal.
Tumor size is the most important prognostic factor. Lesions that are less than 2 cm in diameter have an 80 percent cure rate, but this rate drops to less than 50 percent for cancers that are 5 cm or greater.
The most common initial symptom is rectal bleeding, which occurs in about one half of patients with anal cancer. This may be erroneously attributed to hemorrhoids. About 30 percent of patients have pain or the feeling of a rectal mass. Twenty percent are asymptomatic. Anorectal warts are found in 50 percent of homosexual men with anal cancer.
The known association of cervical cancer with HPV infection and the relationship of cervical and anal cancers to sexual activity resulted in the theory that anal cancer may also be caused by HPV. A subsequent study of 388 patients with anal cancer found HPV DNA in 88 percent of cases. Similar to the case with cervical cancer, HPV type 16 was the subtype most frequently identified. Other factors associated with anal carcinomas that have been identified include cigarette smoking, immunosupression and human immunodeficiency virus infection.
The standard of care for treating tumors of the anal canal has historically been abdominoperineal resection. The anorectum was surgically removed, and the patient was given a permanent colostomy. The reported five-year survival rate following surgery is 40 to 70 percent. The preferred method of treatment has become radiation therapy, given as external-beam or brachytherapy. This modality has a 70 to 90 percent cure rate in selected patients. However, for tumors larger than 5 cm or if lymph nodes are involved, the cure rate is about 50 percent. Complications of radiation therapy include anal ulcers, anal stenosis and necrosis. Approximately 10 percent of such patients ultimately require a colostomy.
Ongoing studies are examining the role of combination therapy that includes radiation and systemic chemotherapy. Several randomized trials to date that have used mitomycin plus radiation have shown a reduction in local failures, a lower likelihood of recurrence, and a lower probability of the need for a colostomy because of disease recurrence. However, a difference in overall survival at five years was not seen. A current multicenter, randomized trial is comparing therapy using a combination of cisplatin and fluorouracil with therapy using mitomycin and fluorouracil.
A key issue that remains to be clarified is the role of cytologic screening for HPV and anal carcinoma in high-risk populations. Early detection, as with other cancers, should ultimately reduce morbidity and mortality from anal carcinoma. Further prospective studies are needed to define the risks and benefits of screening for HPV.