Anal cancer

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Mohamad Alkateb, MBBCh [2]

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 and its 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. Treatment depends on the stage of the disease at the time of diagnosis.

Anal cancer may be classified according to histology into four subtypes: squamous cell carcinoma, adenocarcinoma, lymphoma, and sarcoma.

Anal cancer most commonly arises from squamous cells at the squamocolumnar junction. Other types of anal cancer are adenocarcinoma, lymphoma, and sarcoma.

In 2008-2012, the incidence of anal cancer was estimated to be 1.8 cases per 100,000 individuals in the US.

The most potent risk factor in the development of anal cancer is Human Papillomavirus (HPV). Other risk factors include receptive anal intercourse with multiple sexual partners, smoking, and immunosuppression.

Screening for anal cancer by pap smear is suggested among HIV-positive patients and homosexual men.

Squamous carcinoma of the anus may be caused by HPV infection.

Anal cancer must be differentiated from other diseases that cause anal pain, anal pressure, and hematochezia, such as, anal fissure, and neoplastic ulcers.

Depending on the extent of the tumor at the time of diagnosis, the prognosis may vary. The three major prognostic factors are site (anal canal vs. perianal skin), size (primary tumors <2 cm in size have better prognoses), and lymph nodes involvement.^[1]

The staging of Anal cancer is based on the TNM staging system ^[1]

Symptoms of anal cancer include pain or pressure in the anus or rectum, anal itching and anal discharge.

Common physical examination findings of anal cancer include a lump near the anus and rectal bleeding.

Laboratory Studies

There are no diagnostic lab findings associated with anal cancer.

MRI

Pelvic MRI may be diagnostic of anal cancer.

CT

CT may be helpful in the diagnosis and staging of anal cancer.

Ultrasound

Endoanal ultrasound may be helpful in the diagnosis, staging, determination of the depth of penetration, and to monitor the response to chemo and/or radiation therapy to anal cancer.

Other Imaging Studies

PET–CT may be helpful in anal cancer staging.^[2]

Other Diagnostic Imaging

Anoscopy, proctoscopy, and biopsy maybe helpful in the diagnosis of anal cancer.

The predominant therapy for anal cancer is chemotherapy and radiation.

Surgical resection is not recommended among patients with advanced or metastatic anal cancer.

HPV vaccine is recommended for homosexual men, bisexual men, and women who engage in receptive anal sex to prevent anal cancer. Other primary prevention strategies include smoking cessation and condom use.^[1]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Mohamad Alkateb, MBBCh [2]

Anal cancer may be classified according to histology into four subtypes: squamous cell carcinoma, adenocarcinoma, lymphoma, and sarcoma.

Anal cancer is classified to:

• Squamous cell carcinoma
• Adenocarcinoma
• Lymphoma
• Sarcoma

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Mohamad Alkateb, MBBCh [2]

Anal cancer most commonly arises from squamous cells at the squamocolumnar junction. Other types of anal cancer are adenocarcinoma, lymphoma, and sarcoma.

Common types of anal cancers are:

• Squamous cell carcinoma
• Adenocarcinoma
• Lymphoma
• Sarcoma

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Mohamad Alkateb, MBBCh [2]

Squamous carcinoma of the anus may be caused by HPV infection^[1]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Mohamad Alkateb, MBBCh [2]

Anal cancer must be differentiated from other diseases that cause anal pain, anal pressure, and hematochezia, such as, anal fissure and neoplastic ulcers.

Anal cancer must be differentiated from other diseases that cause anal discomfort and pain with defecation such as hemorrhoids, anal fissure and perianal abscess.

Disease	History	Physical exam findings	Sample image
Hemorrhoids	External hemorrhoids External hemorrhoids are painful as the skin below the punctate line is sensitive to pain.[1] Blood clots may form in external hemorrhoids. Thrombosed external hemorrhoids cause bleeding, painful swelling, or a hard lump around the anus. When the blood clot dissolves, extra skin is left behind. This skin can become irritated or itch. Excessive straining, rubbing, or cleaning around the anus may make symptoms, such as itching and irritation, worse. Internal hemorrhoids The most common symptom of internal hemorrhoids is bright red blood on stool, on toilet paper, or in the toilet bowl after a bowel movement. Internal hemorrhoids that are not prolapsed are usually not painful. Prolapsed hemorrhoids often cause pain, discomfort, and anal itching	Skin examination Inspection of the anal verge may show scratch marks and skin tags. Inspection also may reveal external hemorrhoids or prolapsed internal hemorrhoids. Digital rectal examination Digital rectal examination reveals the size and location of hemorrhoids. Thrombosed hemorrhoids are tender to palpation. Internal hemorrhoids are not palpable by digital rectal examination and the use of anoscope is mandatory.
Anal fissure	Anal fissure usually presents with tearing pain with every bowel movement.[1] Pain usually lasts for minutes to hours after every bowel movement. Patient is typically afraid of going to the bathroom to avoid the pain, which leads to a viscious cycle. The fissure worsens the constipation and the constipation (hard stool) aggravates the fissure. About two-thirds of the patients present with bright red blood streaks on toilet papers or on the surface of stools. May be accompanied by pruritis and discharge.	Most fissures occur in the posterior midline of the anal canal.[2] Skin tags in the perianal area may accompany chronic anal fissures.
Rectal prolapse	Rectal prolapse most commonly occurs in multiparous females over 40 years old.[3] Appears as a progressive mass protrusion from the anus. The protrusion first appears with straining and defecation, then progresses to the degree when it is no longer replaced back. It presents with abdominal discomfort and incomplete defecation. Fecal incontinence and anal discharge. Pain is not usually present.	Mass protruding from the anus.[4] Concentric mucosal rings are characteristic of rectal prolapse.
Perianal abscess	Perianal abscess presents with severe, continuous, dull, aching pain in the perianal area.[5] Pain is exacerbated with bowel movements, but is not exclusive to it. Constipation due to fear of bowel movements. Fever, headache, and chills may accompany the pain. If the abscess starts to drain, discharge of purulent or bloody fluid may be noticed.	Flatulent, erythematous, and tender area of skin overlying the abscess. If abscess is deep, tenderness is elicited with digital rectal examination.
Anal cancer	Rectal bleeding is the most common presentation.[6] Mass sensation in the anus. Mucoid discharge may occur. Patient may give a history of anal condyloma (especially homosexual men).[7] Fecal incontinence.	On digital rectal examination, solid hemorrhagic mass that is firmly fixed to the surrounding structures is noted. Femoral and inguinal lymph nodes may show lymphadenopathy secondary to spread of cancer.
Condylomata acuminata	Patient may give a history of unprotected anal sex with an infected partner. Having multiple sexual partners is a risk factor and should be investigated.[8] Condyloma acuminata presents with painless warts that vary in size, shape, and color. Pruritis and discharge may accompany the warts.	Anal condyloma acuminata may be accompanied by cervical, vaginal, or even ororpharyngeal warts, so the patient should be examined thoroughly.[9]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2] Associate Editor(s)-in-Chief: Mohamad Alkateb, MBBCh [3]

In 2008-2012, the incidence of anal cancer was estimated to be 1.8 cases per 100,000 individuals in the US.

Incidence^[1]

• In women and men who do not engage in anal intercourse with other men – 0.9/100,000
• In HIV negative men who engage in anal intercourse with other men – 35/100,000
• In HIV positive men who engage in anal intercourse with other men – (estimated) 60-70/100,000

• Number of New Cases and Deaths per 100,000: The number of new cases of anal cancer was 1.8 per 100,000 men and women per year. The number of deaths was 0.2 per 100,000 men and women per year. These rates are age-adjusted and based on 2008-2012 cases and deaths.

• Lifetime Risk of Developing Cancer: Approximately 0.2 percent of men and women will be diagnosed with anal cancer at some point during their lifetime, based on 2010-2012 data.^[2]
• Because it is rare and because it occurs in a body part that is rarely discussed, most people are unaware of its existence.

An 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 (90% of the tumors from women, 100% of the tumors from homosexual men, and 58% of tumors from heterosexual men).^[3]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Mohamad Alkateb, MBBCh [2]

The most potent risk factor in the development of anal cancer is Human Papillomavirus (HPV). Other risk factors include receptive anal intercourse with multiple sexual partners, smoking, and immunosuppression.

Common risk factors associated with anal cancer are:

• Human papillomavirus (HPV) infection, notably HPV-16.^[1]

• Sexual activity: Having multiple sex partners or having anal sex, due to the increased risk of exposure to the HPV virus.^[2]

• Smoking: Current smokers are several times more likely to develop anal cancer compared with nonsmokers.^[2]

• Immunosuppression, which is often associated with HIV infection.^[2]

• Being older than 50 years ^[3]

• Frequent anal redness, swelling, and soreness ^[3]

• Having anal fistulas (abnormal openings) ^[3]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Mohamad Alkateb, MBBCh [2]

Screening for anal cancer by pap smear is suggested among HIV-positive patients and homosexual men.

Anal pap smears similar to those used in cervical cancer screening have been studied experimentally for early detection of anal cancer in high-risk individuals.^[1][2]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Mohamad Alkateb, MBBCh [2]

Depending on the extent of the tumor at the time of diagnosis, the prognosis may vary. The three major prognostic factors are site (anal canal vs. perianal skin), size (primary tumors <2 cm in size have better prognoses), and lymph nodes involvement.^[1]

The prognosis of anal cancer depends on the following:^[1]

• Size of tumor
• Location of anal cancer in the anus
• Spread to the lymph nodes

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