by Catherine Forse MD FRCPC
December 20, 2025
Squamous cell carcinoma is a type of cancer that starts in the anus or anal canal, which is the opening at the end of the digestive tract. This cancer develops from squamous cells, which are flat cells that normally line the surface of the anal canal.
Anal squamous cell carcinoma usually grows slowly at first but can spread to nearby tissues and lymph nodes if not treated. With treatment, many cases can be successfully controlled or cured, especially when diagnosed at an early stage.
What causes anal squamous cell carcinoma?
The most important cause of anal squamous cell carcinoma is human papillomavirus (HPV) infection. HPV is a widespread virus that is spread through skin-to-skin and sexual contact. In most people, HPV infection clears on its own. In some cases, however, the virus persists for many years and causes abnormal changes in the cells lining the anus. Over time, these changes can lead to cancer.
About 9 out of 10 cases of anal squamous cell carcinoma are related to HPV, most commonly HPV type 16. Some tumours contain more than one HPV type.
Other factors can increase the risk of developing anal squamous cell carcinoma. These include conditions that weaken the immune system, such as HIV infection or long-term use of immunosuppressive medications. Smoking, a history of other sexually transmitted diseases, and receptive anal intercourse are also associated with a higher risk.
Although chronic inflammation around the anus, such as long-standing perianal Crohn disease, has been suggested as a risk factor, only a very small number of people with these conditions develop anal cancer.
What are the symptoms of anal squamous cell carcinoma?
Common symptoms of anal squamous cell carcinoma include discomfort or pain in the anal area, bleeding, discharge, or a feeling of fullness. Some people notice a lump, an ulcer, or an area of abnormal colour or firmness on examination.
In early disease, the abnormal area may be small and difficult to see. Special examinations, such as high-resolution anoscopy, often with acetic acid application, can help doctors identify subtle lesions.
How common is anal squamous cell carcinoma?
Anal squamous cell carcinoma is uncommon. Rates vary worldwide, with a higher incidence in North America and northern Europe compared with other regions. Most patients are diagnosed in their 60s or later. People with conditions that weaken the immune system, such as HIV infection, tend to be diagnosed at a younger age. The disease is more common in women overall. In men, the risk is strongly influenced by immune status and HPV infection.
How is the diagnosis made?
The diagnosis of anal squamous cell carcinoma is made by examining a biopsy of the abnormal area under the microscope. A biopsy is a small tissue sample taken from the tumour. Imaging studies and clinical examination are then used to determine how far the cancer has spread, but the diagnosis itself is based on the microscopic findings.
When examined under the microscope, anal squamous cell carcinoma shows invasive squamous cells, meaning the cancer cells have grown beyond the normal surface lining of the anal canal and into deeper tissues. These cells usually form clusters, nests, or strands that infiltrate the surrounding tissue.
The tumour cells often show keratinization, meaning they produce keratin, a protein normally made by healthy squamous cells. This finding helps confirm that the tumour started from squamous cells. Pathologists may also see intercellular bridges, which are tiny connections between neighbouring squamous cells and are another feature that supports the diagnosis.
Some anal squamous cell carcinomas show a basaloid growth pattern. In this pattern, the tumour cells are smaller and darker, and they grow in compact nests or cords. Although this appearance looks different from typical squamous cell carcinoma, it represents the same disease and is treated the same way.
A rare form called verrucous squamous cell carcinoma exhibits a thickened surface and a pushing growth pattern, meaning the tumour expands into nearby tissue rather than aggressively infiltrating it. These tumours show very little atypia, which means the cells look relatively close to normal. Verrucous squamous cell carcinoma does not usually spread to lymph nodes or distant organs. However, areas of conventional squamous cell carcinoma can sometimes develop within a verrucous tumour, and for this reason, careful sampling is important.
A special test called immunohistochemistry may be performed in some cases. Many anal squamous cell carcinomas show strong staining for p16, a protein that acts as a marker of HPV-related cancer. These stains can help confirm the diagnosis and exclude other conditions that can look similar under the microscope.
What does tumour grade mean?
Tumour grade describes how abnormal the cancer cells look under the microscope compared with normal squamous cells. In anal squamous cell carcinoma, grade is based on the degree of differentiation, which means how closely the tumour cells resemble normal squamous cells.
Pathologists divide anal squamous cell carcinoma into three grades:
- Well differentiated: A well-differentiated tumour is composed of cancer cells that still resemble normal squamous cells. These tumours usually show clear keratinization and recognizable squamous features.
- Moderately differentiated: A moderately differentiated tumour contains cancer cells that look more abnormal but can still be identified as squamous cells. Keratinization may be present but is often less obvious.
- Poorly differentiated: A poorly differentiated tumour is composed of very abnormal-looking cells that resemble normal squamous cells only minimally or not at all. These tumours may show little or no keratinization, and additional tests such as immunohistochemistry are sometimes needed to confirm the diagnosis.
In general, less differentiated tumours (moderately and poorly differentiated) tend to behave more aggressively and are more likely to spread to lymph nodes or other parts of the body. However, for anal squamous cell carcinoma, tumour stage is usually a more important predictor of outcome than grade, especially because many biopsies sample only part of the tumour and squamous cell carcinomas can show mixed features.
Tumor size
Tumour size is measured after the tumour is removed and examined by a pathologist. The largest measurement is recorded in the pathology report. Tumour size is important because it is used to determine the pathologic tumour stage (pT). Larger tumours are more likely to involve nearby tissues and have a higher risk of recurrence or spread.
Tumor extension
Tumour extension describes how deeply the cancer has grown into the wall of the anal canal and surrounding tissues. Anal squamous cell carcinoma starts in the mucosa, the thin inner lining of the anal canal. As the tumour grows, it can extend into deeper layers, including the submucosa, muscle layer, and perianal soft tissue. In more advanced cases, the tumour can grow through the wall of the anal canal and directly invade nearby organs.
Tumours that extend more deeply are associated with a higher risk of recurrence and spread, including spread to distant organs such as the lungs. Tumour extension can only be accurately assessed by microscopic examination of the tissue.
Perineural invasion
Perineural invasion means that cancer cells were seen growing along or around a nerve. Nerves are responsible for transmitting sensations such as pain, pressure, and temperature. When tumour cells involve a nerve, they can use it as a pathway to spread into surrounding tissues. The presence of perineural invasion is important because it is associated with a higher risk of the cancer returning after treatment.
Lymphovascular invasion
Lymphovascular invasion means that cancer cells were found inside a blood vessel or a lymphatic vessel. Blood vessels carry blood throughout the body, while lymphatic vessels carry lymph fluid to lymph nodes. Cancer cells can use these vessels as pathways to spread to lymph nodes or distant organs. When lymphovascular invasion is present, the risk of lymph node involvement and metastasis increases.
Lymph nodes
Lymph nodes are small structures that help filter lymph fluid and play a role in the immune system. Cancer cells can spread from the primary tumour to lymph nodes through lymphatic vessels. This process is called metastasis.
If lymph nodes were removed during surgery, each one is examined under the microscope.
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Lymph nodes with cancer cells are called positive.
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Lymph nodes without cancer cells are called negative.
Pathology reports usually include:
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The total number of lymph nodes examined.
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The number of lymph nodes that contain cancer cells.
This information is used to determine the pathologic nodal stage (pN).
Margins
A margin is the edge of the tissue that the surgeon cuts to remove the tumour.
Margins are examined to determine whether the tumour was removed entirely.
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A negative margin means no cancer cells are seen at the edge of the tissue.
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A positive margin means cancer cells are present at the cut edge.
A positive margin is associated with a higher risk of the cancer growing back in the same area.
The type of margins examined depends on the procedure performed.
For abdominoperineal resection (APR) specimens, margins include:
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Proximal margin – toward the rectum or sigmoid colon.
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Distal margin – usually in the perianal region.
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Radial margin – tissue surrounding the outside of the anal canal.
For local excisions or endoscopic procedures, margins include:
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Mucosal margin – the inner surface lining.
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Deep margin – tissue beneath the tumour within the anal canal wall.
Treatment effects
If chemotherapy or radiation therapy was given before surgery, your pathologist will assess how much of the tumour remains alive.
Treatment effect is often reported on a scale from 0 to 3:
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0 – No viable cancer cells (complete response).
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1–2 – Partial response with some remaining cancer.
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3 – Extensive residual cancer with little or no response.
Treatment effect helps doctors understand how well the tumour responded to therapy and can influence further management.
How is the pathologic stage (pTNM) determined?
The pathologic stage (pTNM) is determined using the TNM system, which evaluates:
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T (tumour) – size and extent of the primary tumour.
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N (nodes) – spread to lymph nodes.
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M (metastasis) – spread to distant organs (usually based on imaging rather than pathology).
Higher stage numbers generally indicate more advanced disease.
Tumour stage (pT)
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T1 – Tumour 2 cm or smaller.
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T2 – Tumour larger than 2 cm but 5 cm or smaller.
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T3 – Tumour larger than 5 cm.
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T4 – Tumour of any size that has invaded nearby organs such as the bladder, urethra, or vagina (in women).
Nodal stage (pN)
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N0 – No cancer found in lymph nodes.
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N1a – Cancer in inguinal, mesorectal, or internal iliac lymph nodes.
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N1b – Cancer in external iliac lymph nodes.
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N1c – Cancer in both groups above.
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NX – No lymph nodes were examined.
What happens after the diagnosis?
After the diagnosis of anal squamous cell carcinoma is confirmed, additional tests are performed to determine the stage of the cancer and to guide treatment planning. This usually includes imaging studies to evaluate the tumour and nearby lymph nodes.
Most patients are treated with combined chemotherapy and radiation therapy, which is highly effective for anal squamous cell carcinoma and often allows the anus to be preserved without surgery. Surgery is usually reserved for cancers that do not respond completely to treatment or that recur.
During and after treatment, follow-up visits and imaging are used to monitor response. Tumours may continue to shrink for several months after therapy ends, so assessment is often delayed to allow time for a complete response.
In selected cases, newer treatments, such as immunotherapy, may be considered, particularly if the cancer recurs or spreads.
What is the prognosis for a person with anal squamous cell carcinoma?
The most important factor affecting prognosis is the stage of the cancer at diagnosis. Cancers confined to the anal canal have a better outcome than those that have spread to lymph nodes or distant organs.
How well the tumour responds to treatment is also strongly linked to outcome. Many people with anal squamous cell carcinoma are cured with standard therapy.
HIV infection does not worsen cancer-specific survival, although it can increase the risk of treatment-related side effects. Ongoing follow-up is important for monitoring recurrence and managing the long-term effects of treatment.
Questions to ask your doctor
- Is my cancer related to HPV?
- What stage is my anal squamous cell carcinoma?
- Have my lymph nodes been evaluated?
- What treatment is recommended for me?
- How will we know if the treatment is working?
- What follow-up tests will I need after treatment?
- Are there newer treatment options if the cancer comes back?
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