History and exam

Key diagnostic factors

common

presence of risk factors

Key risk factors include human papillomavirus, HIV, immunosuppression, receptive anal intercourse, multiple sexual partners, autoimmune disease, and smoking.

rectal bleeding

The most common presenting symptom, occurring in 45% of patients.[3]

rectal pain

Occurs in 30% of patients.[3]

rectal mass

Occurs in 30% of patients.[3]

Other diagnostic factors

uncommon

anal discharge

May be a presenting symptom of anal cancer.[4] 

anal itching

May be a presenting symptom of anal cancer.[4]

faecal incontinence

May be a presenting symptom of anal cancer.[4]

anal fistula

May be a presenting symptom of anal cancer.[4]

non-healing ulcer

May be a presenting symptom of anal cancer.[4]

inguinal node mass

At the time of presentation, 33% of anal cancers have spread to regional lymph nodes.[17]

Lymph from tumours distal to the dentate line drains mainly to the superficial inguinal nodes, which are more readily palpated on physical examination.[8] Lymph from tumours at and proximal to the dentate (or pectinate) line drains to the anorectal, perirectal, paravertebral, and internal iliac nodes; node enlargement in these regions may only be detectable with imaging.

Most inguinal lymph node metastases are unilateral. Enlarged inguinal lymph nodes are usually <0.5 to 1.0 cm in diameter and non-tender.

features of distant metastasis

Twelve percent of patients have distant metastases at the time of diagnosis.[17]

The para-aortic nodes and the liver are the most common sites of metastatic spread. Lungs, bones, skin, and peritoneum are less frequently affected.[4]

Symptoms of extrapelvic metastatic disease are related to the involved organ.

Risk factors

strong

HPV

Human papillomavirus (HPV) is detectable in 95% of squamous cell carcinoma of the anus.[11] More than 200 types of HPV exist, with differing oncogenic potential. HPV 16 and HPV 18 are high-risk types. HPV 16 accounts for 89% of the positive samples.[11]

Incidence of anal cancer is higher in women with HPV-related gynaecological cancers (cervical, vulvar, and vaginal) or precursor lesions, compared with the general population.[13]

The quadrivalent HPV vaccine has been found to reduce the rate of anal intraepithelial neoplasia in men who have sex with men, and may therefore help to reduce the risk of anal cancer in these patients.[19]

HIV

There is a clear association between HIV and anal canal cancer.

People living with HIV have a significantly increased incidence of anal cancer, compared with people without HIV.[12][13] Incidence increases with age, and is highest in men who have sex with men and people with AIDS.[12][13]

immunosuppression

Solid organ transplant recipients have a 6.8-fold increased incidence of anal cancer, compared with the general population.[14] Patients with haematological malignancies also have a higher risk of squamous cell carcinoma of the anus, compared with the general population.[15]

receptive anal intercourse

The odds of anal cancer are increased in men and women who practice receptive anal intercourse.[20]

multiple sexual partners

The odds of anal cancer are increased in men and women who have had ≥15 sexual partners during their lifetime.[20]

autoimmune disease

Patients with some autoimmune diseases (Crohn's disease, ulcerative colitis, systemic lupus erythematosus, psoriasis, polyarteritis nodosa, and granulomatosis with polyangiitis) have a higher risk of squamous cell carcinoma of the anus compared with the general population.[13][15]

smoking

The odds of anal cancer are increased in men and women who currently smoke, independent of age and other risk factors.[20]

weak

anal intraepithelial neoplasia

Anal intraepithelial neoplasia (AIN) is a precursor lesion of squamous cell carcinoma of the anus which is also associated with HPV infection. Risk of progression to invasive anal cancer after treatment of AIN is low.[21][22][23]​​

The quadrivalent HPV vaccine has been found to reduce the rate of AIN in men who have sex with men, and may therefore help to reduce the risk of anal cancer in these patients.[19]

anal fistula

About a quarter of patients with anal cancer have a fistula at the time of diagnosis.[4] There is an association between benign anorectal disease and cancer, but causation has not been established.[24][25]

In one study, 41% of anal canal carcinomas were preceded by benign anorectal disease for at least 5 years. In another study, men who reported a history of anal fissure or fistula and who have sex with other men had an elevated risk of anorectal squamous cell carcinoma (RR 9.1).[26] It is postulated that chronic inflammation and repeated epithelial regeneration may increase the risk of anal cancer.[26]

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