Cervical cancer Study Guide

📖 Core Concepts Cervical cancer: Malignant growth arising from the cervix (lower uterus) that can invade locally and metastasize. High‑risk HPV: Types 16, 18, 31, 45 (together ≈ 85 % of cases). Viral proteins E6 → degrades p53, E7 → degrades pRb → loss of cell‑cycle control and angiogenesis. Cervical intraepithelial neoplasia (CIN): Precancerous lesion graded CIN 1 (mild), CIN 2 (moderate), CIN 3 (severe/carcinoma‑in‑situ). Staging (FIGO 2018): Clinical & imaging‑based from stage 1A (microscopic) to stage 4B (distant metastasis). Sub‑categories (e.g., 1B3) add tumor size/detail. Treatment pillars: Surgery (cone biopsy, trachelectomy, hysterectomy) – primary for early disease, fertility‑preserving when possible. Radiation (external beam + brachytherapy) – radiosensitive tumor; used when surgery infeasible or for larger disease. Chemoradiotherapy – cisplatin‑based chemo + radiation improves survival in locally advanced disease. Systemic therapy (platinum + paclitaxel ± bevacizumab; pembrolizumab for PD‑L1+). --- 📌 Must Remember Global burden (2022): > 660 k new cases, ≈ 350 k deaths; 8 % of female cancers; 90 % occur in low‑/middle‑income countries. HPV 16/18 cause 75 % of cases; HPV 31/45 add another 10 %. Vaccine efficacy: 92‑100 % against HPV 16/18; Gardasil/Gardasil 9 reduce precancer by 93 % and cancer by 62 %. Screening start ages: WHO ≥ 30 y (≥ 25 y if HIV+); U.S. ≥ 21 y. Screening intervals: HPV test every 5 y; Pap test every 3 y (HIV+ → 3‑5 y HPV). 5‑year survival: Stage 1 ≈ 91 %; Stage 2 ≈ 65 %; Stage 3 ≈ 35 %; Stage 4 ≈ 7 %. Risk multipliers: Current/former smokers with HPV → 2‑3 × invasive cancer risk. ≥ 7 full‑term pregnancies → 4 × risk. Long‑term oral contraceptives ↑ risk in HPV‑positive women. --- 🔄 Key Processes HPV‑driven oncogenesis HPV infects basal cervical epithelium → integration → E6 degrades p53, E7 degrades pRb → unchecked proliferation & VEGF‑driven angiogenesis → CIN → invasive carcinoma. Screening algorithm (high‑resource setting) Primary test: HPV DNA test → if positive, reflex colposcopy (apply acetic acid → visualize lesions). If HPV unavailable, Pap test → LSIL → likely CIN 1 (observe); HSIL → colposcopy/biopsy. Stage‑based treatment decision Stage IA1: cone biopsy ± repeat; fertility‑preserving. Stage IA2–IB1 (<4 cm): radical hysterectomy or chemoradiation; add lymphadenectomy. Stage IB3–IVA: concurrent chemoradiotherapy (cisplatin ± carboplatin). Recurrent/metastatic: platinum + paclitaxel ± bevacizumab; add pembrolizumab if PD‑L1+. --- 🔍 Key Comparisons Vaccine types Bivalent: protects against HPV 16/18. Quadrivalent: protects against HPV 16/18 + 6/11 (genital warts). Nonavalent: adds protection for 5 additional oncogenic types (31, 33, 45, 52, 58). Screening tests HPV test: higher sensitivity, longer interval (5 y). Pap test: cytology, lower sensitivity, shorter interval (3 y). VIA: low‑resource, visual inspection with acetic acid; less accurate than HPV test. Early‑stage vs Locally advanced treatment Early (IA‑IIA): surgery (cone, trachelectomy, hysterectomy) ± adjuvant radiation. Locally advanced (IB3‑IVA): chemoradiotherapy ± immunotherapy; surgery rarely primary. CIN grading CIN 1 (mild) → often regresses; observation. CIN 2/3 (moderate‑severe) → high‑grade lesion; requires excision or ablation. --- ⚠️ Common Misunderstandings HPV vaccine treats existing infection – False: it is prophylactic only. Any abnormal vaginal bleeding = cancer – False: most bleeding is benign; consider timing, intercourse, menopause. Screening starts at 30 for everyone – False: U.S. guidelines start at 21; HIV+ at 25 (WHO). Smoking only harms lungs – False: smoking impairs immune clearance of HPV, markedly increasing cervical cancer risk. --- 🧠 Mental Models / Intuition “Virus → tumor‑suppressor loss → unchecked growth” – Remember E6 → p53 loss, E7 → pRb loss → cells escape checkpoints. Stage = Size + Spread – Visualize a circle (tumor size) with arrows (local extension, nodal involvement, distant metastasis). Screening = Early‑stage “CIN” catch‑all – Think of screening as a net that pulls out precancer before it becomes invasive. --- 🚩 Exceptions & Edge Cases HIV‑positive: start screening at 25 y; screen every 3‑5 y with HPV test. Immunosuppressed (e.g., transplant, IBD meds): may need extra vaccine doses & closer follow‑up. Fertility preservation: consider radical trachelectomy for IA2–IB1 when childbearing desired. High‑grade lesions (CIN 2/3) in pregnant women: may defer definitive treatment until postpartum if disease not rapidly progressive. --- 📍 When to Use Which Screening test: Use HPV DNA when available (higher sensitivity); reserve Pap where HPV testing is limited. Surgical vs Radiation: Choose surgery for early stage with desire for fertility or when tumor ≤ 4 cm and resources allow; choose chemoradiation for tumors > 4 cm, nodal disease, or when surgery not feasible. Chemotherapy agent: Cisplatin → first‑line unless contraindicated (renal dysfunction, neuropathy) → then carboplatin. Immunotherapy: Add pembrolizumab only if tumor expresses PD‑L1 or for high‑risk locally advanced disease after standard chemoradiotherapy. --- 👀 Patterns to Recognize Bleeding after intercourse + HPV risk factors → think early cervical pathology. Pap HSIL → likely CIN 2/3 → immediate colposcopy/biopsy. Tumor > 4 cm on imaging → shift from surgery to chemoradiation. Weight loss, bone pain, leg swelling in a known cervical cancer patient → suspect metastatic spread (bone, lung, abdomen). --- 🗂️ Exam Traps “HPV vaccination eliminates need for screening.” – Wrong; vaccinated women still require screening because vaccines do not cover all oncogenic HPV types. “All stage IA2 cancers are managed with hysterectomy.” – Incorrect; fertility‑preserving trachelectomy or chemoradiation may be chosen. “Smoking doubles risk regardless of HPV status.” – Misleading; risk amplification is most pronounced among HPV‑positive women. “A negative Pap test rules out cervical cancer.” – False; Pap has lower sensitivity; HPV testing is more reliable, especially in high‑risk populations. “CIN 1 never progresses to cancer.” – Over‑simplification; while most regress, a small fraction can progress, so appropriate follow‑up is needed.