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Anal cancer

Background

Overview

Definition
Anal squamous cell cancer is a neoplastic disease arising from malignant transformation of squamous cells found in the mucosa of the anal canal and anal margin.
1
Pathophysiology
The majority of anal squamous cell cancers are caused by infection with oncogenic strains of HPV, particularly types 16 and 18. These strains of HPV encode tumor suppressor proteins E6 and E7, and their interactions with intracellular proteins p53 and retinoblastoma lead to changes in cell growth and regulation, apoptosis, and immortalization, leading to malignant disease.
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Epidemiology
The incidence of anal squamous cell cancer in the US is estimated at 1.3 cases per 100,000 person-years.
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Disease course
Initially, anal squamous cell cancer undergoes locoregional spread, with early involvement of the anal musculature, which is very close to the underlying sphincters. Anal canal cancer grows circumferentially, which may result in stenosis of the anal sphincter. When the sphincter is invaded, the tumor spreads into the ischiorectal fossae, the prostatic urethra and bladder in men, and the vagina in women. Anal cancer may spread via the lymphatic vessels to the perirectal nodes or to nodes at the bifurcation of the superior rectal artery. Hematogenous spread occurs in < 10% of cases, and liver metastasis is more common than lung or bone metastasis. Metastasis to distant organs such as the brain and iris has also been reported.
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Prognosis and risk of recurrence
The 5-year survival rate of patients with T1-T2 anal squamous cell cancer is estimated at 80-90%, while it is estimated at 50% for patients with T4 disease.
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Guidelines

Key sources

The following summarized guidelines for the evaluation and management of anal cancer are prepared by our editorial team based on guidelines from the American Academy of Family Physicians (AAFP 2024), the Society for Immunotherapy of Cancer (SITC 2023), the European Society of Medical Oncology (ESMO 2021), the American Society of Colon and Rectal Surgeons (ASCRS 2018), and the British HIV ...
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Screening and diagnosis

Indications for screening
As per AAFP 2024 guidelines:
Consider performing digital anal rectal examination every 2-5 years in MSM aged ≥ 50 years.
C
Consider performing digital anal rectal examination each year in HIV-positive MSM aged ≥ 35 years.
C
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Diagnostic investigations

History and physical examination
As per ESMO 2021 guidelines:
Perform digital anorectal examination for the detection of lesions in the anal area.
A
Perform clinical examination, including DRE (and vaginal examination in female patients) and palpation of the inguinal lymph nodes, for the assessment of tumor extenet.
B

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  • Diagnostic imaging

  • HPV testing

  • HIV testing

  • Screening for other intraepithelial neoplasia

Diagnostic procedures

Endoscopy: as per ASCRS 2018 guidelines, perform endoscopic evaluation to determine tumor extension and assess for metastatic disease.
B

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  • FNA

  • Biopsy and pathology

Medical management

General principles: as per ESMO 2021 guidelines, refer and discuss all patients with anal tumors in a multidisciplinary team meeting with a pre-specified interest in anal cancer.
B

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  • Management of in-situ lesions

  • Management of local/locoregional disease (indications)

  • Management of local/locoregional disease (radiotherapy techniques and doses)

  • Management of anal margin involvement

  • Management of advanced/metastatic disease (chemotherapy)

  • Management of advanced/metastatic disease (immunotherapy/targeted therapy)

  • Management of advanced/metastatic disease (surgery and local therapies)

Therapeutic procedures

Endoscopic ablation: as per ASCRS 2018 guidelines, consider performing ablative therapy with conventional anoscopy or high-resolution anoscopy in patients with high-grade squamous intraepithelial lesions.
C

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  • Colostomy

Surgical interventions

Wide-local excision: as per ESMO 2021 guidelines, consider performing local excision for definite treament of patients with early anal margin cancer (cT1N0M0) aiming to achieve histological clearance of > 1 mm without damaging the anal sphincter muscle.
C

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  • Abdominoperineal resection

Specific circumstances

Patients with HIV/AIDS: as per ASCRS 2018 guidelines, treat patients with HIV infection who present with anal cancer as the first manifestation of their immunosuppression according to the same regimens as immunocompetent patients, provided they are not medically deconditionned.
B

Patient education

Counseling on treatment adherence: as per ASCRS 2018 guidelines, counsel patients on avoiding missed treatments, because they are strongly associated with poor disease control.
B

Preventative measures

HPV vaccination
As per ASCRS 2018 guidelines:
Offer HPV immunization in < 26 years old males and females in order to prevent anal squamous cell cancer.
B
Do not offer immunization in individuals with anal dysplasia for the secondary prevention of dysplasia and cancer.
D

Follow-up and surveillance

Assessment of treatment response: as per ESMO 2021 guidelines, assess tumor response after chemoradiotherapy in 26 weeks as an optimum time point.
B
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  • Surveillance for toxicity

  • Follow-up

  • Patients with locally recurrent or residual disease