Anal Cancer

Original Author: Chuk Anibueze
Last Updated: December 22, 2017
Revisions: 16

Anal cancer is relatively rare. It accounts for ~4% of colorectal cancers and has a UK incidence of approximately 1 in 100,000.

In this article, we shall look at the risk factors, clinical features and management of anal cancer.


The majority (~80%) of anal cancers are squamous cell carcinomas, which arise from below the dentate line (pectinate line).

Most of the remainder (~10%) are adenocarcinomas arising from the upper anal canal epithelium and the crypt glands. Rarer anal tumours include melanomas and anal skin cancers.

Anal Intraepithelial Neoplasia

Anal intraepithelial neoplasia (AIN) may precede the development of invasive squamous anal carcinoma, and can affect either the perianal skin or anal canal. AIN is strongly linked to infection with human papilloma virus (HPV).

The grading of AIN is dependent on the degree of cytological atypia, and the depth of that atypia in the epidermis. High-grade AIN (grade 2 or 3) is premalignant and may progress to invasive cancer.

Fig. 1 - The anal columns, anal valves and pectinate line.

Figure 1 – The anal columns, anal valves, and pectinate line

Risk Factors

The risk factors for developing anal cancer include:

  • HPV infection (accounts for 80-90% of cases)
    • Especially HPV-16 and HPV-18
  • HIV infection
  • Increasing age
  • Smoking
  • Immunosuppressant medication
  • Crohn’s disease

Clinical Features

The main symptoms of anal cancer are:

  • Pain and rectal bleeding
    • These are the most common symptoms & occur in ~50% of patients.
  • Anal discharge
  • Pruritus
  • Palpable mass

Perianal infection and fistula-in-ano can be seen in locally invasive disease. If the anal sphincters are invaded, faecal incontinence and tenesmus can also occur.

On examination, the perineum and perianal region should be screened for any ulceration or the presence of wart-like lesions. In women, a vaginal examination is important to assess for the presence of additional vulval or vaginal lesions.

A Digital Rectal Examination (DRE) should be attempted, although may not be feasible due to pain. If a mass is palpable, remember to document the distance from the anal verge where it is felt and the fraction of the anal circumference which it occupies. The inguinal lymph nodes should be examined for lymphadenopathy*.

*Lymph from the area below the dentate line drains to the superficial inguinal nodes, whereas the anal canal and rectum above the dentate line drain into the mesorectal, para-aortic, and paravertebral nodes.

Differential Diagnosis

The differential diagnoses for any anal pathology can be divided into benign causes and malignant causes:

Benign Malignant

Anal fissure


Anal warts

Low rectal cancer

Skin cancer




Initial Investigations

Following initial examination, proctoscopy should be performed to obtain a better initial assessment of the anal canal.

All patients with suspected anal cancer should then undergo examination under anaesthetic. This allows for much better assessment for tumour size and invasion of local structures and allows a biopsy to be taken for histological confirmation. If one suspects immunosuppression on a background of high risk behaviour, an HIV test should be considered.

In women, a smear test can be performed to exclude any cervical intraepithelial neoplasia (CIN) and any further biopsies if signs of vulval intraepithelial neoplasia (VIN) are present.


Once a biopsy has been taken and anal cancer has been confirmed, further staging investigations are required:

  • USS-guided Fine Needle Aspiration (FNA) of any palpable inguinal lymph nodes
  • CT thorax-abdomen-pelvis for distant metastases
  • MRI Pelvis to assess the extent of local invasion (T stage)
Fig. 2 - Diagram showing the (1) Stage 1 and (2) Stage 4 anal cancer metastasis

Figure 2 – Diagram showing the (1) Stage 1 and (2) Stage 4 anal cancer metastasis


A multidisciplinary approach must be used in the management of anal cancer, including oncologists, general surgeons, radiologists, and specialist nurses.

Chemotherapy and Radiotherapy

In recent years, there has been a shift in the management of anal cancers. Chemo-radiotherapy is the first choice treatment for most anal tumours, over surgical treatment*.

Treatment is usually external beam radiotherapy to the anal canal and inguinal lymph nodes, combined with dual-chemotherapy agents, such as mitomycin C and 5-fluorouracil.

*One exception is in early T1N0 carcinomas, where wide local excision may be the preferred treatment to avoid the increased morbidity associated with chemoradiotherapy.  

Surgical Management

Surgical excision may be considered but this is usually reserved for management of advanced disease, after failure of chemoradiotherapy, or in early T1N0 carcinomas.

The majority of patients requiring surgical intervention for anal cancer will receive an abdominoperineal resection (APR), yet for some a posterior or total pelvic exenteration is required (this is often only done at specialist centres)

Most recurrences occur in the first 3 years. After remission, patients should be reviewed every 3–6 months for a period of 2 years, and 6–12 monthly until 5 years. Patients tend to relapse locally and regionally rather than metastasise.

Fig 3 - Abdominoperineal resection.

Fig 3 – Abdominoperineal resection.


Chemoradiation-related pelvic toxicity is the most common short term complication, including dermatitis, diarrhoea, proctitis and cystitis, leucopenia, and thrombocytopenia. Longer term, some patients may develop fertility issues, faecal incontinence, vaginal dryness, erectile dysfunction, and rectovaginal fistula.

Prognosis is related to the initial staging of the tumour and lymph node spread; the table below shows the predicted 5-year survival based on tumour staging.

Tumour Stage 5 Year Survival (%)
I 69.5
II 61.8
IIIa 45.6
IIIb 39.6
IV 15.3


Key Points

  • Pain and bleeding are the most common symptoms in anal cancer
  • All patients with suspected anal cancer should undergo examination under anaesthetic
  • Chemo-radiotherapy is first line curative treatment for the majority of patient


Question 1 / 5
What is the most common type of anal cancer?


Question 2 / 5
Which virus is anal intraepithelial neoplasia strongly linked with?


Question 3 / 5
Which lymph nodes are most likely to be enlarged in anal squamous cell carcinoma?


Question 4 / 5
What is the definitive diagnostic investigation in anal cancer?


Question 5 / 5
What is the most common surgical treatment of anal cancer?


Medico Digital

Further Reading

Anal cancer: ESMO-ESSO-ESTRO Clinical Practice Guidelines for diagnosis, treatment and follow-up
R. Glynne-Jones et al., Annals of Oncology

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