Cervical Cancer
Cervical cancer is the fourth most common female cancer worldwide, predominantly caused by human papillomavirus (HPV), with UK screening and HPV vaccination programmes significantly reducing incidence.
Key Facts
- HPV types 16 and 18 are responsible for approximately 70% of cervical cancers
- UK incidence: approximately 3,200 new cases per year; mortality approximately 850 deaths per year
- NHS cervical screening programme: HPV primary screening from age 25 (every 3 years until 49, then every 5 years until 64)
- Gardasil 9 vaccine offered to all children aged 12-13 (since 2019); covers HPV 6, 11, 16, 18, 31, 33, 45, 52, 58
- FIGO staging is used; early-stage (IA-IB1) treated with surgery; advanced stage (IB2+) treated with chemoradiotherapy
- Squamous cell carcinoma accounts for 70-80%; adenocarcinoma 20-25%
- Referral under 2-week wait pathway for suspected cervical cancer (visible lesion, persistent contact/IMB)
- Concurrent chemoradiotherapy (cisplatin 40mg/m² weekly + external beam RT + brachytherapy) is standard for locally advanced disease
Overview
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
Clinical Presentation
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)
Differential Diagnosis
| Diagnosis | Key Features | Investigation |
|---|---|---|
| Cervical ectropion | Postcoital bleeding, smooth red area around os | Speculum, cervical smear |
| Cervical polyp | Pedunculated lesion from os, contact bleeding | Speculum, polypectomy |
| Endometrial cancer | Postmenopausal bleeding, no visible cervical lesion | TVS, endometrial biopsy |
| Vaginal cancer | Visible vaginal lesion, bleeding | Examination, biopsy |
| Cervicitis (Chlamydia/gonorrhoea) | Discharge, cervical inflammation | STI screen |
Diagnosis / Investigation
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)
Management
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
Prognosis
- 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
Other Relevant Information
FIGO Staging (2018 Revision)
| Stage | Description |
|---|---|
| IA1 | Stromal invasion ≤3mm depth |
| IA2 | Stromal invasion 3-5mm depth |
| IB1 | Tumour ≤2cm |
| IB2 | Tumour 2-4cm |
| IB3 | Tumour ≥4cm |
| IIA | Vaginal involvement (upper 2/3), no parametrial invasion |
| IIB | Parametrial invasion |
| IIIA | Lower 1/3 vagina |
| IIIB | Pelvic sidewall/hydronephrosis |
| IIIC | Lymph node involvement (IIIC1 pelvic, IIIC2 para-aortic) |
| IVA | Bladder/rectal mucosa invasion |
| IVB | Distant metastases |
UK HPV Vaccination Programme
| Feature | Detail |
|---|---|
| Vaccine | Gardasil 9 (9-valent) |
| Schedule | Single dose for age 12-13 (from 2023) |
| Coverage | HPV 6, 11, 16, 18, 31, 33, 45, 52, 58 |
| Expected impact | 90% reduction in cervical cancer |