Medical condition
Anal cancer is a cancer which arises from the anus, the distal opening of the gastrointestinal tract. Symptoms may include bleeding from the anus or a lump near the anus. Other symptoms may include pain, itchiness, or discharge from the anus. A change in bowel movements may also occur.
Risk factors include human papillomavirus (HPV), HIV/AIDS, receptive anal sex, smoking, and many sexual partners. Anal cancer is typically a squamous cell carcinoma. Other types include adenocarcinoma, small cell carcinoma, and melanoma. Diagnosis is suspected based on physical examination and confirmed by tissue biopsy.
Prevention includes avoiding risk factors and HPV vaccination. Standard treatment may include radiation therapy, chemotherapy, and surgery. About 8,300 people are diagnosed a year in the United States, representing about 0.5% of new cancers. Onset is typically after the age of 45. Women are affected more often than men. The number of cases has increased since the 1990s. The five-year survival rate in the United States is 68%.
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.
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.
Staging.
Pathologic TNM staging of anal carcinomas:
Primary tumor (pT)
Regional lymph nodes (pN)
Distant metastasis (pM)
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, scientists surmise that HPV vaccination may reduce the incidence of anal cancer.
The efficacy of the vaccine against HPV types 16 and 18 in naive women ≤26 years old has been shown to be between 91-100% but is lower when individuals are vaccinated irrespective of baseline HPV infection at 76%.
In 2010, Gardasil was approved in the US 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.
As the incidence of anal cancer has increased in recent years, screening and early detection of anal intraepithelial neoplasia (AIN) has become a necessity in patients at risk. This screening detects premalignant lesions, which are highly prevalents, and improves the staging of lesions after treatment.
Anal Pap smears similar to those used in cervical cancer screening have been studied for early detection of anal cancer in high-risk individuals. In 2011, an HIV clinic 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. A similar study was performed in women with a history of cervical cancer or high-grade cervical intraepithelial neoplasia. More than 30% had abnormal anal Pap smears and one third of those already had anal intraepithelial neoplasia.
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.
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 the combination of chemotherapy and radiation treatment 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 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. For stages I to III anal squamous cell carcinoma, using cisplatin instead of mitomycin C (MMC) in chemoradiation therapy doesn't improve overall survival or slow down the cancer compared to the standard treatment of 5-FU plus MMC. Although cisplatin might cause fewer blood-related side effects, 5-FU combined with MMC is still the preferred treatment for nonmetastatic anal cancer. A 2024 systematic review found that chemoradiation therapy (CRT) with 5-FU and Mitomycin C improves locoregional control and colostomy-free survival compared to radiation alone, though with increased acute hematologic toxicity.
Metastatic or recurrent disease.
10 to 20% of patients treated for anal cancer will develop distant metastatic disease following treatment. 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. JD Hainsworth developed a protocol that includes Taxol and Carboplatinum along with 5-FU.
Prognosis.
Median survival rates for people with distant metastases range from 8 to 34 months. Surgical resection with permanent colostomies was the standard treatment until the 1970s, yielding 5-year overall survival of approximately 50%. The best overall survival rates are seen after combined radiation therapy combined with chemotherapy (5-FU + Mitomycin) in people with T2N0 and T3N0 categories of disease (5-y overall survival: 82%). The 5-year overall survival rates of patients with T4 with no involved lymph nodes, T3 with involved lymph nodes, and T4 with involved lymph nodes disease after the combined treatment is 57%, 57%, and 42%, respectively.
Radiation therapy side effects (and occurrence rates) include acute (27%) and late (17%) dermatological toxicities, acute (14%) and late (27%) gastrointestinal toxicities, and chronic pelvic radiation disease (1-10%), e.g., irreversible lumbosacral plexopathy.
Epidemiology.
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 human papillomavirus (HPV).
United States.
In 2014 about 7,060 new cases of anal cancer were diagnosed in the United States (4,430 in women and 2,630 in men). It is typically found in adults, average age early 60s. In 2019, an estimated 8,300 adults will be diagnosed with anal cancer.
In the United States, an estimated 800 to 900 people die of anal cancer annually.
United Kingdom.
Anal cancer accounts for less than 1% of all cancer cases and deaths in the United Kingdom. Around 1,200 people were diagnosed with the disease in 2011, and around 310 people died in 2012.
References.
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