Anal Squamous Cell Carcinoma

What anal squamous cell carcinoma is

The anal canal is the last 3 to 4 cm (about 1.5 inches) of the digestive tract, opening at the anus. Its lining changes from rectal-type cells to squamous cells (flat, skin-like cells). Most anal cancers arise from these squamous cells, often in the transformation zone, where the two cell types meet. This is similar to where cervical cancer develops, and both are driven by HPV.

Cancer usually develops slowly from precancerous changes called anal intraepithelial neoplasia (AIN) or high-grade squamous intraepithelial lesions (HSIL). Anal cancer is uncommon, but rates have been rising, especially in women over 50.

Symptoms

• Rectal bleeding: bright red blood on toilet paper or in the bowl, the most common symptom.
• Pain or pressure in the anal area.
• Itching that persists.
• A lump at the anal edge or inside the canal.
• Discharge of mucus or pus.
• Change in bowel habits or narrow stools.
• Swollen lymph nodes in the groin.

About 1 in 5 people have no symptoms at diagnosis. Because these symptoms overlap with hemorrhoids, anal fissures and warts, anal cancer is often diagnosed late.

Anal cancer vs hemorrhoids

Any anal symptom that does not improve with treatment should be examined.

Causes and risk factors

• HPV infection: high-risk types, mainly HPV-16 and HPV-18. HPV is spread through intimate skin-to-skin contact, and most infections clear on their own.
• HIV: people living with HIV, especially men who have sex with men, have a much higher risk.
• Receptive anal intercourse and multiple sexual partners.
• History of HPV-related cancer or precancer of the cervix, vulva or vagina.
• Weakened immunity: organ transplant, long-term immunosuppressive drugs.
• Smoking: increases the chance that HPV infection persists.
• Age: most common over 50.
• Genital warts indicate HPV exposure (usually low-risk types, but they often coexist with high-risk types).

Diagnosis

1. Digital rectal exam: a gloved finger feels for lumps and checks lymph nodes in the groin.
2. Anoscopy or high-resolution anoscopy: a short tube with a light, sometimes with magnification and a vinegar stain, to view the lining.
3. Biopsy: a sample of any abnormal area confirms the diagnosis.
4. Staging tests: MRI of the pelvis to measure the tumor and nodes, CT of the chest, abdomen and pelvis, and often a PET-CT scan.
5. HIV testing for anyone diagnosed with anal cancer.

Stages

Staging (TNM) considers tumor size (2 cm and 5 cm are key cutoffs), spread to lymph nodes, and spread to distant organs, usually the liver or lungs.

Treatment

Chemoradiation (main treatment)

Most anal squamous cell carcinomas are treated with radiation therapy combined with chemotherapy (commonly 5-fluorouracil or capecitabine with mitomycin), over about 5 to 6 weeks. This approach, first developed by Dr. Norman Nigro, cures most people with localized disease and preserves the anal sphincter, avoiding a permanent colostomy.

Response is checked with exams and scans over the following months. Tumors can keep shrinking for up to 6 months after treatment ends.

Surgery

• Local excision: for very small, early tumors at the anal margin.
• Abdominoperineal resection: removal of the anus and rectum with a permanent colostomy, reserved for cancer that persists or returns after chemoradiation.

Advanced disease

Chemotherapy (such as carboplatin and paclitaxel) and immunotherapy (checkpoint inhibitors) are used for cancer that has spread.

Side effects

Skin soreness in the treated area, diarrhea, tiredness, low blood counts, and later bowel urgency, sexual dysfunction, vaginal narrowing and infertility can occur. Supportive care and pelvic rehabilitation help.

Outlook

Five-year relative survival in the US is around 80% for cancer confined to the anus, about two-thirds when it has spread to nearby lymph nodes, and much lower for distant spread. Regular follow-up with exams, anoscopy and imaging for at least 5 years checks for recurrence.

Prevention and screening

• HPV vaccination: recommended at age 11 to 12 and through age 26, and for some adults up to 45 after discussion with a doctor. It prevents infection with the types that cause most anal cancers.
• Screening for high-risk groups: people living with HIV and some other high-risk groups may be offered anal cytology (an anal Pap test), HPV testing and high-resolution anoscopy. A large NCI-funded trial (ANCHOR) found that treating high-grade anal precancer in people with HIV reduced progression to cancer.
• Stop smoking.
• Condoms reduce but do not eliminate HPV transmission.

Frequently asked questions

What are the first signs of anal cancer?

The most common first sign is rectal bleeding. Others include anal itching, pain or pressure, a lump near the anus, discharge, and swollen glands in the groin. Many people assume these are hemorrhoids, so symptoms that do not improve with treatment should be examined.

Is anal cancer caused by HPV?

Most cases are. About 90% of anal squamous cell carcinomas are linked to persistent infection with high-risk HPV, especially HPV-16. HPV is very common and usually clears on its own; cancer develops only in a small fraction of people with long-term infection.

Can anal cancer be cured?

Yes. Most people with cancer limited to the anus and nearby lymph nodes are cured with chemoradiation, usually without needing a permanent colostomy. Outcomes are best when it is found early, which is why persistent anal symptoms should be checked.

How do I tell anal cancer from hemorrhoids?

Hemorrhoids are soft, often come and go, and improve within 1 to 2 weeks of treatment. Anal cancer tends to cause a firm, persistent lump, continuing pain or bleeding, and sometimes groin lymph node swelling. Only an examination and biopsy can tell them apart for certain.

Who should be screened for anal cancer?

Screening is mainly recommended for higher-risk groups, especially people living with HIV, and may be considered for organ transplant recipients and women with a history of HPV-related vulvar cancer. Ask your doctor whether anal cytology or high-resolution anoscopy is right for you.