Overview
Cervical Cancer
1. Overview
Cervical cancer is a malignancy of the cervix (neck of the womb). It is largely preventable thanks to screening and vaccination. Historically a leading killer of women, incidence has dropped dramatically in developed countries but remains high globally.
It is almost exclusively caused by persistent infection with High-Risk Human Papillomavirus (HPV).
Epidemiology
- Age: Bimodal peak (25-29 and 50-59).
- Cause: HPV DNA is found in >99.7% of cases.
2. Pathophysiology
┌─────────────────────────────────────────────────────────────────────────────┐
│ THE HPV PATHWAY TO CANCER │
├─────────────────────────────────────────────────────────────────────────────┤
│ │
│ ┌─────────────────────────────────────────────────────────────────────┐ │
│ │ HPV INFECTION (Types 16 & 18) │ │
│ │ • Sexually transmitted. 80% of women infected in lifetime. │ │
│ │ • Usually cleared by immune system in 18-24 months. │ │
│ └─────────────────────────────────────────────────────────────────────┘ │
│ ↓ │
│ ┌─────────────────────────────────────────────────────────────────────┐ │
│ │ PERSISTENCE & INTEGRATION │ │
│ │ • Viral DNA integrates into host cell DNA. │ │
│ │ • Oncoproteins E6 and E7 produced. │ │
│ │ • E6 disables p53 (The guardian of the genome). │ │
│ │ • E7 disables Rb (Retinoblastoma protein). │ │
│ │ • Result: Uncontrolled cell division. │ │
│ └─────────────────────────────────────────────────────────────────────┘ │
│ ↓ │
│ ┌─────────────────────────────────────────────────────────────────────┐ │
│ │ CIN (Cervical Intraepithelial Neoplasia) │ │
│ │ • Pre-cancerous changes in the Transformation Zone. │ │
│ │ • CIN 1 -> CIN 2 -> CIN 3 (Carcinoma in situ). │ │
│ │ CIN (Cervical Intraepithelial Neoplasia) │
│ • Pre-cancerous changes in the Transformation Zone. │
│ • CIN 1 -> CIN 2 -> CIN 3 (Carcinoma in situ). │
└─────────────────────────────────────────────────────────────────────┘
### Image: HPV Screening Pathway
### Image: Transformation Zone Anatomy
### The Role of Cofactors
│ │
└─────────────────────────────────────────────────────────────────────────────┘
3. Clinical Features
Early Stage
- Asymptomatic: Detected on screening.
- Post-Coital Bleeding (PCB): Bleeding after sex. The cardinal symptom.
- Intermenstrual Bleeding (IMB).
Late Stage
- Pain: Pelvic/Back pain (invasion of sacral plexus).
- Fistulae: Vesicovaginal (urine leaks) or Rectovaginal.
- Renal Failure: Ureteric obstruction (Hydronephrosis) - common cause of death (Uremia).
4. Diagnosis & Staging (FIGO 2018)
Diagnosis: Colposcopy + Biopsy (LLETZ or Punch). Staging: Clinical Staging (exam under anesthetic) + MRI Pelvis.
Staging: FIGO 2018 (Revised). Key Change: Lymph node involvement (micrometastases or macrometastases) automatically assigns Stage IIIC. Key Change: Size cut-off for IB is now 2cm and 4cm.
| Stage | Definition | Treatment Principle |
|---|---|---|
| Stage IA | Microscopic disease. | |
| IA1 | <3mm depth. | LLETZ or Simple Hysterectomy. |
| IA2 | 3-5mm depth. | Radical Hysterectomy (or Trachelectomy). |
| Stage IB | Visible lesion confined to cervix. | |
| IB1 | <2cm size. | Radical Hysterectomy + Nodes. |
| IB2 | 2-4cm size. | Radical Hysterectomy + Nodes. |
| IB3 | >4cm size. | Chemoradiotherapy (Bulky disease). |
| Stage II | Invades beyond uterus but NOT pelvic wall/lower 1/3 vagina. | |
| IIA | Upper 2/3 Vagina. (IIA1 <4cm, IIA2 >4cm). | Chemoradiotherapy (Preferable). |
| IIB | Parametrial Invasion. | CHEMORADIOTHERAPY (Surgery contra-indicated). |
| Stage III | Pelvic wall / Lower 1/3 vagina / Hydronephrosis / Nodes. | |
| IIIA | Lower 1/3 Vagina. | Chemoradiotherapy. |
| IIIB | Pelvic Wall or Hydronephrosis (Kidney failure). | Chemoradiotherapy. |
| IIIC | Lymph Nodes (Pelvic IIIC1 / Para-aortic IIIC2). | Chemoradiotherapy + Boost to nodes. |
| Stage IV | Bladder/Rectum mucosa or Distant Mets. | |
| IVA | Adjacent organs (Bladder/Bowel). | Exenteration (rare) or Chemorad. |
| IVB | Distant Mets (Lung, Liver, Bone). | Palliative Chemo (Carboplatin/Paclitaxel) + Bevacizumab. |
Crucial Point: Once it spreads beyond the cervix (Stage 2B+), surgery provides no benefit over Chemoradiotherapy and causes more morbidity. We switch to Chemo-Rad.
5. Screening & Prevention
Primary Prevention: Vaccination
- Gardasil 9: Protects against 9 strains (16, 18, 31, 33, 45, 52, 58 + 6, 11).
- Given to boys and girls aged 12-13.
- Effectiveness: Has virtually eliminated cervical cancer in vaccinated cohorts (e.g., Scotland study).
Secondary Prevention: Screening (NHS Model)
- Ages 25-64.
- Frequency: Every 3 years (25-49), Every 5 years (50-64).
- Method: High-Risk HPV testing first ("HPV Primary").
- If HPV Negative -> Routine recall.
- If HPV Positive -> Check Cytology (Smear).
- If Cytology Abnormal (Dyskaryosis) -> Colposcopy.
Colposcopy
- Microscope to view cervix.
- Stains: Acetic Acid (turns CIN white - Acetowhite) and Iodine (Schiller's test - CIN stays yellow, normal stains brown).
- Abnormal Features: Acetowhite epithelium, Mosaicism (chicken wire blood vessels), Punctation (dots), Atypical Vessels.
Image: Colposcopy View
6. Management Algorithm
┌─────────────────────────────────────────────────────────────────────────────┐
│ CERVICAL CANCER MANAGEMENT │
├─────────────────────────────────────────────────────────────────────────────┤
│ │
│ FERTILITY SPARING? (For young women, Stage IA2 - IB1 <2cm) │
│ • **Radical Trachelectomy**: │
│ - Removal of Cervix + Upper Vagina + Parametrium + Nodes. │
│ - Uterus is preserved and stitched to the vagina (Neocervix). │
│ - A permanent suture (Cerclage) is placed to hold the pregnancy. │
│ • **Outcomes**: │
│ - Pregnancy rate ~50%. │
│ - High risk of preterm delivery / miscarriage. │
│ - Delivery MUST be by C-Section (No cervix to dilate). │
│ └─────────────────────────────────────────────────────────────────────┘ │
│ ↓ │
│ ┌─────────────────────────────────────────────────────────────────────┐ │
│ │ SURGERY (Stage 1B - 2A) │ │
│ │ • Radical Hysterectomy (Wertheim's). │ │
│ │ • Removes: Uterus, Cervix, Upper Vagina, Parametrium, Lymph Nodes. │ │
│ │ • Note: Unlike simple hysterectomy, ureters must be dissected out. │ │
│ └─────────────────────────────────────────────────────────────────────┘ │
│ ↓ │
│ ┌─────────────────────────────────────────────────────────────────────┐ │
│ │ CHEMORADIOTHERAPY (Stage 2B - 4A) │ │
│ │ • The "Gold Standard" for locally advanced disease. │ │
│ │ • External Beam Radiotherapy (EBRT). │ │
│ │ • Concurrent Cisplatin (Chemo sensitizes cells to radiation). │ │
│ │ • Brachytherapy: Radioactive source placed INSIDE cervix. │ │
│ └─────────────────────────────────────────────────────────────────────┘ │
│ │
└─────────────────────────────────────────────────────────────────────────────┘
7. Prognosis
- Stage 1: >95% 5-year survival.
- Stage 4: <15% 5-year survival.
8. Complications
Of Treatment
- Lymphedema: Leg swelling from node removal.
- Menopause: If ovaries removed or irradiated.
- Vaginal Stenosis: Shortening/narrowing (affects sexual function).
- Bladder Atony: Nerve damage during Radical Hysterectomy.
9. Key Clinical Pearls
Exam-Focused Points
- HPV 16 & 18: Cause 70% of cancers.
- HPV 6 & 11: Cause Genital Warts (not cancer).
- Risk Factors: COCP (slight risk), Smoking (Squamous risk), HIV, Early sexual debut.
- Hydronephrosis: Automatically upstages to Stage 3B.
- Trachelectomy: The buzzword for fertility-sparing surgery.
- Vaccine: Does NOT treat existing cancer/infection. Preventative only.
Common Exam Scenarios
- 32yo woman with Post-Coital Bleeding. Cervix looks normal. Next step? (Urgent Colposcopy/Smear triggers referral). "A normal looking cervix does not rule out cancer".
- Stage 2B (Parametrial invasion). Treatment? (Chemoradiotherapy - NOT surgery).
- 25yo with CIN3 on biopsy. Treatment? (LLETZ / Loop excision).
10. Patient Explanation
What causes it?
"Almost all cases are caused by a common virus called HPV, which is passed on through sexual contact. Most people get HPV and clear it naturally. In some women, it stays in the cervix and slowly changes the cells over many years from normal, to pre-cancer, to cancer."
Will I need a hysterectomy?
"If we catch it early, yes, removing the womb is often the cure. If it has started to spread into the tissues around the cervix, surgery won't reach it all, so we use a combination of chemotherapy and radiotherapy which is very effective."
11. Evidence & Guidelines
Key Guidelines
| Guideline | Organization | Year | Key Points |
|---|---|---|---|
| Cervical Cancer | ESGO / ESTRO | 2018 | Detailed staging/treatment. |
| Screening | NHS / PHE | 2020 | HPV Primary screening protocol. |
Landmark Trials
LACC Trial (2018):
- compared Open vs Minimally Invasive (Laparoscopic/Robot) Radical Hysterectomy.
- Result: Open surgery had BETTER survival.
- Impact: Minimally invasive surgery is now generally NOT recommended for cervical cancer (practice changing).
Evidence-Based Recommendations
| Recommendation | Evidence Level |
|---|---|
| HPV Vaccination | High |
| Chemo-Rad for Stage 2B+ | High |
| Open Surgery > Laparoscopic | High (LACC Trial) |
13. References
- Ramirez PT, et al. Minimally Invasive versus Abdominal Radical Hysterectomy for Cervical Cancer (LACC). N Engl J Med. 2018.
- Cibula D, et al. The European Society of Gynaecological Oncology/European Society for Radiotherapy and Oncology/European Society of Pathology Guidelines for the Management of Patients with Cervical Cancer. Int J Gynecol Cancer. 2018.