Case senerio
Completion requirements
A 49-year-old woman presents with a 6-month history of severe anal pain, rectal bleeding during defecation, tenesmus, and mucoid discharge. Her symptoms were initially attributed to hemorrhoids, resulting in delayed diagnosis.
Viral Status and Biomarkers
- HIV-1 positive and receiving antiretroviral therapy (ART) with virologic suppression.
- CD4 count: 420 cells/µL.
- High-risk human papillomavirus (HPV) type 16 positive.
- Strongly positive for p16 on immunohistochemistry (IHC).
Histopathology
Biopsy confirms infiltrating, non-keratinizing squamous cell carcinoma (SCC) of the anal canal.
Staging Work-up
Pelvic imaging demonstrates:
- Primary tumour measuring 4.2 cm, consistent with T2 disease.
- Extension into the internal sphincter.
- Bilateral inguinal and mesorectal lymph node involvement.
- No distant metastases on chest and abdominal computed tomography (CT).
Clinical stage: Stage IIIB (T2 N1b M0).
Fellow Discussion Questions
1. HPV, Biomarkers, and HIV
- How do high-risk HPV E6 and E7 oncoproteins promote carcinogenesis and p16 overexpression?
- What is the clinical significance of HPV-16 and p16 positivity in anal SCC?
- How does well-controlled HIV infection affect chemoradiotherapy tolerance, treatment delivery, and outcomes?
2. Definitive Chemoradiotherapy
- Why is definitive chemoradiotherapy preferred for most non-metastatic anal SCC, rather than surgery as the initial treatment?
- Compare 5-fluorouracil (5-FU) plus mitomycin C (MMC) with cisplatin-based regimens.
- What is the role of intensity-modulated radiation therapy (IMRT) in reducing treatment-related toxicity?
3. Response Assessment and Salvage Surgery
- How should tumour response be assessed after definitive chemoradiotherapy?
- What constitutes a clinical complete response (cCR), and when should response be reassessed?
- When is salvage abdominoperineal resection (APR) indicated for persistent or recurrent disease?
4. Resource-Constrained Setting
- How can treatment be adapted when there is limited access to linear accelerators, treatment interruptions, or mitomycin C shortages?
- What evidence supports alternative systemic regimens such as capecitabine-based treatment?
- How can treatment planning reduce financial and logistical barriers for patients paying out of pocket?
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