Anal Cancer

Filed as a single comprehensive page mirroring the source chapter's own organization — anal squamous cell carcinoma (SCC) is the dominant entity (~85% of anal cancers) and gets the most detailed treatment, but the chapter (and this page) also covers the other, much rarer malignancies that arise at the same anatomic site (adenocarcinoma, verrucous carcinoma, melanoma, Paget disease, basal cell carcinoma, GIST) since they share one staging/evaluation framework and one anatomic location, matching the pattern already used for Anorectal Sexually Transmitted Infections and Pruritus Ani (many distinct entities, one clinical/organizational framework).

Epidemiology and risk factors

SCC accounts for ~85% of anal cancers; incidence is rising at roughly 2.7%/year. WHO histologic classification distinguishes squamous, adenocarcinoma, melanoma, and other rare types. Major risk factors: HIV infection, other causes of immunosuppression (transplant recipients), HPV infection (especially oncogenic subtypes — see Anal Intraepithelial Neoplasia for the fuller HPV/dysplasia biology), smoking, multiple sexual partners, anoreceptive intercourse, and a prior history of cervical/vulvar/vaginal intraepithelial neoplasia (CIN) or AIN. This risk-factor profile overlaps heavily with Anal Intraepithelial Neoplasia's (AIN is anal cancer's histologically confirmed precursor lesion) and with Anorectal Sexually Transmitted Infections's HPV/HIV content.

Anatomy relevant to staging

The anal canal (proximal to the dentate line, extending to the anorectal ring) is distinguished from the perianal skin (distal to the anal verge) — this distinction drives both histogenesis (see Perianal SCC below) and lymphatic drainage, and by extension nodal staging. Proximal to the dentate line, lymphatic drainage follows the superior rectal vessels to the inferior mesenteric and internal iliac nodal basins. Distal to the dentate line (anal canal below the dentate line, and perianal skin), drainage is to the inguinal and femoral nodes. See Colorectal Anatomy & Embryology for the foundational dentate-line/anal-transition-zone anatomy this staging logic builds on.

Evaluation and staging

History and physical exam include digital rectal exam, anoscopy, inguinal lymph node palpation, and (in women) gynecologic exam given the shared HPV risk with cervical/vulvar/vaginal disease. Radiologic evaluation: CT chest/abdomen/pelvis for metastatic workup, PET for nodal/metastatic assessment, and pelvic MRI for local tumor/nodal detail.

Staging uses the AJCC 8th edition TNM system, specific to anal canal cancer — a different T/N/M schema from Colorectal Cancer Staging (TNM) (which is colon/rectal-cancer-specific; that page is built from a different source, Sabiston Ch52 - Colorectal Neoplasia & Colon Cancer Surgery). T-category is based on greatest tumor dimension (T1 ≤2cm, T2 2–5cm, T3 >5cm, T4 invading adjacent organ(s)); N-category reflects regional (perirectal, internal iliac, inguinal) node involvement; M reflects distant metastasis. Full stage groupings combine T/N/M into Stage I–IV per the source chapter's Table 20.4 (not reproduced digit-for-digit here; treat this page as a summary, not a replacement for the current AJCC manual, for an actual staging determination — same caveat already noted on Colorectal Cancer Staging (TNM)).

Perianal squamous cell carcinoma

Distinct histogenetic origin from anal canal SCC — perianal SCC arises from keratinizing squamous epithelium (cytokeratin markers CK5/6 and CK13) rather than the anal transition zone epithelium (CK7/18/19) that anal canal SCC arises from — and carries a better prognosis. Treated more like a skin cancer: wide local excision is the mainstay, with chemoradiation reserved for advanced or margin-positive disease.

Anal canal squamous cell carcinoma

Chemoradiotherapy, not surgery, is the primary treatment for anal canal SCC — a major departure from most other GI malignancies. This traces to the Nigro protocol (combined mitomycin/5-fluorouracil plus radiation, developed as neoadjuvant therapy before an planned APR, but found to produce complete responses without surgery in most patients — establishing chemoradiation as definitive treatment). Subsequent trials refined the regimen:

• ACT I and RTOG 98-11 both compared mitomycin-based to cisplatin-based chemoradiation regimens; mitomycin-based regimens are generally preferred based on these comparisons.
• Capecitabine has been investigated as an oral alternative to infusional 5-FU.
• Cetuximab and other EGFR-inhibitor-based intensification strategies have shown unacceptable toxicity and are not recommended.

Radiation therapy: the RTOG 98-11 multifield protocol is a commonly referenced technique; minimum 45 Gy to the primary tumor is standard, with IMRT (intensity-modulated radiation therapy) preferred over older techniques for its improved toxicity profile.

Inguinal lymph node metastases

Present in ~13% of patients at diagnosis. Fine-needle aspiration (FNA) is used to confirm suspicious nodes. Surgical excision of involved inguinal nodes is not required before chemoradiation — radiation is the primary treatment for nodal disease as well as the primary tumor.

Surgery

Surgery's role in anal canal SCC is now limited: local excision is reserved for superficially invasive T1N0 disease, and abdominoperineal resection (APR) is reserved as salvage therapy for persistent or recurrent disease after chemoradiation, not as primary treatment. Large perineal wounds after salvage APR often require flap reconstruction, most often a VRAM (vertical rectus abdominis myocutaneous) flap.

Anal cancer and HIV

NCCN guidelines recommend treating people living with HIV per the same guidelines as HIV-negative patients — no treatment modification is recommended based on HIV status alone, though HIV-positive patients have historically been noted (elsewhere in the anal-disease literature, e.g. Anorectal Sexually Transmitted Infections) to tolerate chemoradiation toxicity less well and to have higher recurrence rates in some series; the chapter does not resolve this tension and simply states the guideline position.

Surveillance

Initial follow-up is typically 8–12 weeks after completion of chemoradiation. The ACT II trial demonstrated that response can be meaningfully delayed: up to 72% of patients who had not achieved a complete response by 11 weeks went on to achieve complete response by 26 weeks — supporting a watch-and-wait approach to a partial response before concluding treatment has failed, rather than proceeding immediately to salvage surgery.

Anal adenocarcinoma

Accounts for ~20% of anal cancers. Staged and treated similarly to Rectal Cancer (rather than to anal SCC) given its glandular origin, but carries worse survival than either rectal adenocarcinoma or anal SCC, per a National Cancer Database analysis cited in the chapter.

Verrucous carcinoma (Buschke-Löwenstein tumor)

This is the same entity already covered from a different angle in Anorectal Sexually Transmitted Infections's "Giant condyloma (Buschke-Löwenstein tumor)" section (ASCRS Ch18) — that page frames it primarily as an HPV-driven condyloma-spectrum lesion (treatment: wide local excision with 1cm margins, malignant transformation risk reported up to 56%, 65% recurrence). This chapter (Ch20) frames the same lesion from the oncology side: a large, exophytic, cauliflower-like lesion associated with HPV types 6 and 11, with an explicit and unresolved classification controversy — some authors consider it a benign lesion with invasive potential, others a slow-growing, well-differentiated variant of SCC — and reports a malignant transformation rate of 40–60% (broadly consistent with, though not identical to, Ch18's "up to 56%" figure; the two chapters' numbers are not reconciled against each other, reported as each source states). Treated the same way regardless of classification stance: wide local excision, as detailed on the Anorectal Sexually Transmitted Infections page.

Melanoma

Rare and aggressive. No dedicated anal-melanoma TNM staging system exists; the chapter instead references the Falch staging classification (Table 20.5 in the source). Molecular testing for BRAF and c-KIT mutations is relevant to treatment selection — imatinib is used for c-KIT-positive tumors (the same drug class used for Gastrointestinal Stromal Tumors (GIST), though via a different mutation).

Perianal Paget disease (perianal intraepithelial adenocarcinoma)

Closes a forward reference from Pruritus Ani (ASCRS Ch17/Ch19), where Paget disease was already named as a refractory-pruritus differential (typically seventh decade of life; slowly expanding, sharply demarcated erythematous plaque — eczematous, crusting, or ulcerated). This chapter adds the fuller oncologic management content: classification and management is summarized in the source chapter's Table 20.6; mapping biopsies (multiple biopsies around the lesion) are used to define disease extent before surgery, since Paget cells can extend microscopically well beyond the visible lesion margin; wide local excision is the central treatment, with frozen-section margin control preferred given the propensity for subclinical spread. As on the Pruritus Ani page, underlying colonic/GI malignancy should be excluded, since perianal Paget disease can be associated with an underlying adenocarcinoma.

Basal cell carcinoma

Rare in the anal region; not HPV-associated (unlike anal SCC and verrucous carcinoma). Treated with local excision.

Gastrointestinal stromal tumor (GIST)

Rare in the anus — anal GISTs make up only a small fraction (the chapter states ~5%) of all GISTs. See Gastrointestinal Stromal Tumors (GIST) for the full disease biology (interstitial-cell-of- Cajal origin, KIT/CD117 immunohistochemistry, mitotic-index risk stratification, imatinib-based treatment algorithm) — that page's content, from a different textbook source (Sabiston Ch50 - Infectious Enteritis & Small Bowel Neoplasms), is not anus-specific but applies directly. This chapter adds only the anus-specific summary: c-KIT/CD117 positivity, imatinib for larger or ulcerated tumors, surgical excision as the mainstay for resectable disease.

Related pages

• Anal Intraepithelial Neoplasia — the histologically confirmed precursor lesion to anal canal SCC; this page's epidemiology/risk-factor content builds directly on that page's HPV biology.
• Anorectal Sexually Transmitted Infections — HPV/HIV background; and see the Verrucous carcinoma section above for the direct content overlap with that page's Giant condyloma section (Ch18).
• Colorectal Anatomy & Embryology — dentate-line/anal-transition-zone anatomy this page's staging/lymphatic-drainage content builds on; closes that page's Ch20 forward reference.
• Pruritus Ani — Paget disease, Bowen's disease (cutaneous SCC in situ), and cloacogenic carcinoma were named there as refractory-pruritus differentials (Ch17/19); closes that page's Ch20 forward reference.
• Rectal Cancer — anal adenocarcinoma is staged/treated similarly to rectal adenocarcinoma.
• Gastrointestinal Stromal Tumors (GIST) — fuller GIST biology; anal GIST is rare and largely inherits that page's content.
• Anal Stenosis — already named wide local excision of Paget's/Bowen's disease as a stenosis cause; this page provides the fuller oncologic-management content for that excision.
• Presacral Tumors — shares the VRAM-flap reconstruction technique for large pelvic/perineal defects after salvage APR; that chapter also reasons by analogy to anal SCC's chemoradiotherapy efficacy when discussing malignant presacral cysts.

Open items / gaps

• Textbook chapter, not primary literature; the trial data cited (ACT I, RTOG 98-11, ACT II) are the chapter authors' synthesis, not independently re-verified against the primary trial publications.
• The AJCC 8th-edition TNM staging table (T/N/M criteria and full stage groupings, source Table 20.4) is summarized at a high level here, not reproduced in full digit-for-digit detail — treat this page as a summary, not a replacement for the current AJCC Cancer Staging Manual, for an actual staging determination (same caveat as Colorectal Cancer Staging (TNM)).
• The verrucous carcinoma / Buschke-Löwenstein classification controversy (benign-with-invasion- potential vs. SCC variant) is reported as unresolved by the chapter itself — flagged here rather than resolved.
• HIV-status treatment-tolerance/recurrence questions (noted under "Anal cancer and HIV" above) are not resolved by this chapter; NCCN's "treat the same" guideline position and the historically-noted tolerability/recurrence concerns are both reported as-is, not reconciled.
• This chapter's opening pages incidentally overlapped with the start of ASCRS Ch21, "Presacral Tumors" (Kelley & Dozois) — that chapter's content is not yet ingested; a forward reference will be added if any page here should point to it once Ch21 is written.