Key Facts

Cervical cancer is a largely preventable malignancy through HPV vaccination and screening. The majority of cases are caused by persistent high-risk HPV infection. Early detection through screening dramatically improves outcomes.

Epidemiology

• UK incidence: approximately 3,200 new cases per year (14th most common cancer in women)
• Mortality: approximately 850 deaths per year in the UK
• Peak incidence: 30-34 years
• Incidence declining due to screening; expected to decline further with HPV vaccination
• 99.7% of cervical cancers are HPV-related

Aetiology

• Persistent high-risk HPV infection: types 16 (60%), 18 (10-15%), 31, 33, 45, 52, 58
• Risk factors: early sexual debut, multiple sexual partners, immunosuppression (HIV), smoking (doubles risk), long-term COC use (>5 years), high parity, co-infection with other STIs
• Protective: HPV vaccination, condom use, cervical screening

Pathophysiology

• HPV E6 and E7 oncoproteins inactivate tumour suppressors p53 and Rb respectively
• Persistent infection leads to CIN (cervical intraepithelial neoplasia): CIN1 → CIN2 → CIN3 → invasive carcinoma over 10-20 years
• Squamous cell carcinoma arises from the transformation zone
• Adenocarcinoma arises from endocervical glandular cells

Early Disease

• Often asymptomatic (detected on screening)
• Postcoital bleeding
• Intermenstrual bleeding
• Offensive vaginal discharge (blood-stained or watery)

Advanced Disease

• Pelvic pain
• Leg oedema (lymphatic obstruction)
• Haematuria (bladder invasion)
• Rectal bleeding (rectal invasion)
• Renal failure (ureteric obstruction)
• Lower limb DVT

Red Flags

• Postcoital bleeding in any age group
• Visible cervical lesion on speculum examination
• Persistent intermenstrual bleeding not responding to treatment
• Postmenopausal bleeding with abnormal cervix
• Unexplained renal failure in a woman (bilateral ureteric obstruction)

Bedside

• Speculum examination: visible lesion (exophytic/ulcerative), bleeding, discharge
• Bimanual and rectal examination: assess parametrial involvement, tumour size

Bloods

• FBC, U&Es, LFTs (baseline and assess renal function)
• SCC antigen (squamous cell marker)

Imaging

• MRI pelvis: first-line for local staging (tumour size, parametrial invasion, lymph node involvement)
• CT chest/abdomen/pelvis: for distant metastases
• PET-CT: increasingly used for staging and treatment response assessment

Special Tests

• Cervical biopsy: punch biopsy under colposcopy for visible lesions; LLETZ for CIN
• EUA (examination under anaesthesia): for clinical staging and biopsy if needed
• Cystoscopy/sigmoidoscopy: if bladder or rectal involvement suspected (Stage IVA)

Non-pharmacological

• MDT discussion (gynaecological oncology, clinical oncology, radiology, pathology, CNS)
• Patient education and psychological support
• Fertility counselling for young women

Pharmacological

• Concurrent chemoradiotherapy for locally advanced disease (IB2 and above):
  • Cisplatin 40mg/m² IV weekly (for 5 cycles) concurrent with radiotherapy
  • External beam radiotherapy (45-50 Gy in 25 fractions) + intracavitary brachytherapy
• Pembrolizumab (anti-PD-1): approved for recurrent/metastatic cervical cancer with PD-L1 expression (KEYNOTE-826 trial)
• Bevacizumab: added to chemotherapy for recurrent/metastatic disease

Surgical/Interventional

• Stage IA1: cone biopsy or simple hysterectomy (fertility-sparing: cone biopsy)
• Stage IA2-IB1: radical hysterectomy (Wertheim) with bilateral pelvic lymphadenectomy; or radical trachelectomy if fertility desired
• Stage IB2-IVA: primary chemoradiotherapy (surgery not recommended for bulky disease)
• Pelvic exenteration: for central recurrence after radiotherapy (anterior, posterior, or total)

Referral Criteria

• Visible cervical lesion: urgent 2-week wait referral to gynaecological oncology
• Persistent unexplained postcoital or intermenstrual bleeding: 2-week wait
• Abnormal cervical screening result: refer for colposcopy

• Overall 5-year survival: 60-65%
• Stage IA: 95% 5-year survival
• Stage IB: 80-85%
• Stage II: 60-70%
• Stage III: 30-40%
• Stage IV: 15-20%
• With HPV vaccination, cervical cancer could potentially be eliminated in coming decades
• Recurrence: 10-20% for early stage; 50-70% for advanced stage

FIGO Staging (2018 Revision)

UK HPV Vaccination Programme