II. Epidemiology

  1. Rare malignancy (0.5% of all cancers in U.S., 2% of gastrointestinal cancers)
    1. Incidence: 9760 (in U.S. 2023, accounted for 0.5% of all new cancers)
    2. Deaths: 1870 (in U.S. 2023, accounted 0.3% of all cancer deaths)
  2. Gender
    1. Higher Incidence in women by Factor X2-3
  3. Age
    1. Overall peak age: 35 to 49 years
    2. Women age >50 to 64 years (esp. >65 years)

III. Risk Factors

  1. HPV Infection (>80% of cases, esp. HPV16)
    1. Coincides with increased Anal Cancer risk in women with CIN 3 or Cervical Cancer
    2. Genital Wart history also associated
  2. Sexually Transmitted Infection and Related Risks
    1. HIV Infection (aside from HPV, highest risk for Anal Cancer, esp. in MSM)
    2. Anal Intercourse
    3. Increased number of sexual partners
    4. Men who have Sex with Men (MSM)
  3. Immunocompromised States
    1. Solid Organ Transplant recipient
    2. Autoimmune disorders (e.g. SLE, Inflammatory Bowel Disease)
  4. Other risks
    1. Tobacco Abuse

IV. Types

  1. Anal Squamous Cell Carcinoma (ASCC, 80% of Anal Cancers)
    1. ASCC develops at the squamous to columnar epithelial junction
    2. Associated with several specific genetic mutations
  2. Anal adenocarcinoma (5-10% of Anal Cancers)
    1. Staged as ASCC, but treated as Colorectal Cancer (e.g. chemoradiation followed by resection)
  3. Other uncommon to rare Anal Cancers
    1. Lymphoma
    2. Gastrointestinal Stroma tumors
    3. Melanoma
    4. Neuroendocrine tumors

V. Precautions

  1. Delayed presentation is common >6 months (e.g. social stigma)
  2. Initial misdiagnosis is common (e.g. Hemorrhoids)

VI. Symptoms

  1. Often asymptomatic
  2. Rectal Bleeding
  3. Fecal Incontinence (or anal leakage)
  4. Pruritus Ani
  5. Anorectal Pain
  6. Anal or rectal mass Sensation
  7. Anal canal tissue prolapse

VII. Signs

  1. Rectal lesion (may be palpable)
  2. Fecal Occult Blood (may be positive)
  3. Inguinal Lymph Nodes (may be palpable)
  4. Anoscopy may be performed (or deferred to surgeon)

IX. Labs

  1. Complete Blood Count (CBC)
  2. Comprehensive metabolic panel
  3. HIV Test
  4. HPV Testing (anal)
  5. Pap Smear and HIV Testing (women)

X. Diagnostics

  1. Anal mass biopsy or fine needle aspirate
    1. Tissue diagnosis
  2. Advanced Imaging
    1. Evaluate for local and metastatic disease
    2. Imaging per surgery and oncology recommendations
      1. Staging CT/PET
      2. Phased-array pelvic MRI

XI. Staging: TNM

  1. Tumor (T)
    1. T0: No tumor evidence
    2. Tis: HGSIL or carcinoma in situ
    3. T1: Tumor <= 2 cm
    4. T2: Tumor >2 to 5 cm
    5. T3: Tumor >5 cm
    6. T4: Any tumor size invading adjacent organs (e.g. vagina, Urethra or Bladder)
  2. Lymph Node (N)
    1. Nx: Lymph Nodes not assessed
    2. N0: No regional Lymph Node involvement
    3. N1: Node involvement (node metastases)
      1. N1a: Inguinal, mesorectal, or internal iliac node involvement
      2. N1b: External iliac node involvement
      3. N1c: External iliac node AND any N1a node involvement
  3. Metastases (M)
    1. M0: No distant metastases
    2. M1: Distant Metastases
  4. Overall Staging
    1. High Grade Intraepithelial Lesion (Carcinoma In-situ, Bowen's Disease)
      1. Stage 0: TisN0M0
    2. Localized Anal Cancer
      1. Stage 1: T1N0M0
      2. Stage 2a: T2N0M0
      3. Stage 2b: T2N0M0
    3. Advanced Anal Cancer
      1. Stage 3a: T1-2N1M0
      2. Stage 3b: T4N0M0
      3. Stage 3c: T3-4N1M0
    4. Metastatic Anal Cancer
      1. Stage 4: M1, with any T and any N

XII. Management: Anal Cancer

  1. Chemoradiation Therapy (CRT)
    1. CRT is the mainstay of treatment for Anal Cancer (Chemotherapy combined with external beam radiation)
    2. Specific regimens are per oncology, but common regimens are listed here as of 2024
      1. Localized and Advanced Cancer: Fluorouracil (5FU) and Mitomycin C (MMC)
      2. Metastatic Anal Cancer: Carboplatin and Paclitaxel
  2. Surgery
    1. Chemotherapy and radiation have largerly replaced surgical management since the 1970s
    2. However, local excision may be considered in Stage 1 Anal Cancer
    3. Salvage abdominal perineal resection may also be considered for recurrent disease
  3. Immunotherapy
    1. Immune Checkpoint Inhibitor (e.g. PD-1 Monoclonal Antibody, PDL-1 Monoclonal Antibody)
      1. Used in some cases of advanced Anal Cancer and metastatic Anal Cancer

XIII. Management: High Grade Intraepithelial Lesion (HGSIL, Carcinoma In-situ, Bowen's Disease)

  1. Surveillance without treatment has historically been an option, but is no longer recommended
    1. Outcomes are significantly better with local treatment of HGSIL
    2. Palefsky (2022) N Engl J Med 386(24):2273-82 +PMID: 35704479 [PubMed]
  2. Treatment protocols
    1. Lesion ablation (e.g. Infrared Coagulation, electrocautery, laser) with or without excision
    2. Topical treatments (Imiquimod and Fluorouracil)

XV. Resources

Images: Related links to external sites (from Bing)

Related Studies

Ontology: Malignant neoplasm of anal canal (C0153445)

Concepts Neoplastic Process (T191)
ICD9 154.2
ICD10 C21.1
SnomedCT 93669004, 187762000, 363352004
English Malignant neoplasm of anal canal, Anal canal, Malig neop of anal canal, malignant neoplasm of anal canal, cancer of anal canal, malignant neoplasm of anal canal (diagnosis), Anal canal cancer, Anal canal cancer NOS, Malig neopl anal canal, Anal canal neoplasms malignant, Cancer of anal canal, Malignant tumor of anal canal, Malignant tumour of anal canal, Malignant tumor of anal canal (disorder)
Italian Tumori maligni del canale anale, Cancro del canale anale, Tumore maligno del canale anale, Cancro del canale anale, NAS
Dutch anaalkanaalkanker NAO, anaalkanaalkanker, maligne neoplasma van het anaalkanaal, Maligne neoplasma van anaal kanaal, anaalkanaalneoplasmata maligne
French Cancer du canal anal SAI, Tumeur maligne du canal anal, Cancer du canal anal, Tumeurs malignes du canal anal
German Karzinom des Analkanals NNB, boesartige Neubildung des Analkanals, Krebs des Analkanals, Boesartige Neubildung: Analkanal, Anale und kolorektale Neubildungen boesartig
Portuguese Cancro do canal anal, Neoplasia maligna do canal anal, Cancro do canal anal NE, Neoplasias malignas do canal anal
Spanish Cáncer del conducto anal NEOM, Cáncer del conducto anal, Neoplasia maligna del canal anal, neoplasia maligna del conducto anal (trastorno), neoplasia maligna del conducto anal, tumor maligno del conducto anal (trastorno), tumor maligno del conducto anal, Neoplasias malignas del conducto anal, tumor maligno del canal anal
Japanese 悪性肛門管新生物, 肛門管癌, 肛門管の悪性新生物, 肛門管癌NOS, コウモンカンガン, コウモンカンノアクセイシンセイブツ, アクセイコウモンカンシンセイブツ, コウモンカンガンNOS
Czech Novotvary análního kanálu maligní, Maligní nádorové onemocnění análního kanálu, Maligní novotvar análního kanálu, Maligní nádorové onemocnění análního kanálu NOS
Korean 항문관의 악성신생물
Hungarian Anális csatorna neoplasiái, rosszindulatú, Végbélrák k.m.n., Analis csatorna rákja, Analis csatorna malignus neoplasiája

Ontology: Malignant anorectal neoplasm (C0854175)

Concepts Neoplastic Process (T191)
Italian Tumore maligno dell'ano-retto, Tumori maligni dell'anoretto, Tumore maligno dell'ano-retto NAS
Dutch anorectaal neoplasma maligne NAO, anorectaal neoplasma maligne, anorectale neoplasmata maligne
French Tumeur maligne anorectale SAI, Tumeur maligne anorectale, Tumeurs anorectales malignes
German boesartige anorektale Neubildung NNB, Boesartige anorektale Neubildungen, boesartige anorektale Neubildung
Portuguese Neoplasia anorrectal maligna NE, Neoplasias anorrectais malignas, Neoplasia anorrectal maligna
Spanish Neoplasia anorrectal maligna NEOM, Neoplasias anorrectales malignas, Neoplasia anorrectal maligna
Japanese 肛門直腸の悪性新生物NOS, 悪性肛門直腸新生物, 肛門直腸の悪性新生物, アクセイコウモンチョクチョウシンセイブツ, コウモンチョクチョウノアクセイシンセイブツ, コウモンチョクチョウノアクセイシンセイブツNOS
Czech Maligní novotvary řiti a konečníku, Novotvar anorektální oblasti maligní, Maligní anorektální novotvar NOS
English Malignant anorectal neoplasm NOS, Malignant anorectal neoplasms, Malignant anorectal neoplasm
Hungarian Rosszindulatú anorectalis neoplasmák, Anorectalis malignus neoplasiák k.m.n., Anorectalis malignus neoplasiák