Key Facts

This entry covers cervical cancer from the oncology treatment perspective. Cervical cancer is highly preventable through vaccination and screening. Treatment is stage-dependent, with concurrent chemoradiotherapy being standard for locally advanced disease.

Epidemiology

• UK incidence: approximately 3,200 cases per year
• Mortality: approximately 850 deaths per year
• Peak incidence: 30-34 years
• Declining incidence due to screening and expected to decline further with HPV vaccination

Aetiology

• Persistent high-risk HPV infection (types 16, 18 most important)
• Risk factors: early sexual debut, multiple partners, immunosuppression, smoking, long-term COC

Pathophysiology

• Squamous cell carcinoma (70-80%): arises from transformation zone
• Adenocarcinoma (20-25%): arises from endocervical glandular cells
• HPV E6/E7 oncoproteins inactivate p53/Rb
• CIN progression over 10-20 years: CIN1 → CIN3 → invasive cancer
• Spread: direct invasion (parametria, vagina, bladder, rectum) → lymphatic (pelvic, para-aortic) → haematogenous (lung, liver, bone)

Early Disease

• Postcoital bleeding, intermenstrual bleeding
• Vaginal discharge (blood-stained/watery)
• Often asymptomatic (detected on screening)

Advanced Disease

• Pelvic pain, leg oedema, renal failure (ureteric obstruction)
• Haematuria, rectal bleeding (local invasion)
• Fistulae (vesicovaginal, rectovaginal) in very advanced/recurrent disease

Red Flags

• Visible cervical lesion on speculum
• Postcoital bleeding in any age group
• Unexplained renal failure in a woman

Bedside

• Speculum and bimanual/rectal examination

Bloods

• FBC, U&Es (renal function), LFTs
• SCC antigen (squamous marker)

Imaging

• MRI pelvis: local staging
• CT CAP: distant staging
• PET-CT: increasingly used for staging and response assessment

Special Tests

• Cervical biopsy: histological confirmation
• EUA: clinical staging
• Cystoscopy/sigmoidoscopy if bladder/rectal involvement suspected

Non-pharmacological

• MDT discussion
• Fertility counselling for young women
• Psychological support

Pharmacological

• Early-stage (IA-IB1): surgery ± adjuvant RT if high-risk features (positive margins, LVI, deep invasion)
• Locally advanced (IB2-IVA): concurrent chemoradiotherapy:
  • Cisplatin 40mg/m² IV weekly × 5-6 cycles
  • EBRT 45-50 Gy in 25 fractions
  • Intracavitary brachytherapy (total equivalent dose >80 Gy to point A)
  • Treatment completed within 56 days (prolongation worsens outcomes)
• Metastatic/recurrent:
  • Pembrolizumab + cisplatin/carboplatin + paclitaxel ± bevacizumab (KEYNOTE-826)
  • Tisotumab vedotin (antibody-drug conjugate targeting tissue factor; innovaTV 204)
• Adjuvant RT ± concurrent cisplatin: after radical hysterectomy with high-risk features (Sedlis criteria, Peters criteria)

Surgical/Interventional

• Cone biopsy / simple hysterectomy: Stage IA1 without LVI
• Radical hysterectomy (Wertheim) + pelvic lymphadenectomy: Stage IA2-IB1 (open approach preferred after LACC trial)
• Radical trachelectomy: fertility-sparing for Stage IA2-IB1 (tumour <2cm)
• Pelvic exenteration: central recurrence after RT (anterior, posterior, or total)
• Sentinel lymph node mapping: emerging for early-stage

Referral Criteria

• Visible cervical lesion: urgent 2-week wait
• Confirmed cervical cancer: specialist gynaecological oncology centre
• All women: HPV vaccination recommended for prevention

• Overall 5-year survival: 60-65%
• Stage IA: 95%
• Stage IB: 80-85%
• Stage II: 60-70%
• Stage III: 30-40%
• Stage IV: 15-20%
• Concurrent chemoradiotherapy reduces risk of death by 30-40% compared to RT alone
• HPV vaccination expected to make cervical cancer a rare disease in coming decades

Treatment by FIGO Stage

Key Trials