Cervical Cancer
Summary
Cervical cancer is a malignancy arising from the uterine cervix, predominantly caused by persistent infection with high-risk human papillomavirus (HPV), particularly types 16 and 18. It is the fourth most common cancer in women worldwide and is largely preventable through HPV vaccination and cervical screening. The majority (80%) are squamous cell carcinomas, with adenocarcinomas comprising most of the remainder. Cervical screening programmes have dramatically reduced incidence and mortality in developed countries through detection and treatment of pre-invasive disease (CIN). Symptoms include postcoital bleeding, intermenstrual bleeding, and abnormal vaginal discharge. Staging uses the FIGO system, and treatment ranges from local excision (early stage) to radical hysterectomy or chemoradiotherapy (advanced stage).
Key Facts
- Prevalence: 4th most common cancer in women globally; ~3,200 cases/year in UK
- Cause: Persistent high-risk HPV infection (16, 18 account for 70%)
- Histology: Squamous cell carcinoma (80%), Adenocarcinoma (15-20%)
- Prevention: HPV vaccination (Gardasil 9) and cervical screening
- UK screening: Ages 25-64; HPV primary testing since 2019
- Pre-invasive disease: CIN (Cervical Intraepithelial Neoplasia) grades 1-3
- Classic symptom: Post-coital bleeding (PCB)
- Staging: FIGO staging (clinical + imaging from 2018)
- Cure rates: Stage IA — near 100%; Stage IVB — <20% 5-year survival
- Treatment milestone: Concurrent chemoradiotherapy (cisplatin) improved survival (Green et al. 1999)
Clinical Pearls
"PCB = Urgent 2WW": Post-coital bleeding in any woman warrants urgent investigation. While many causes are benign, cervical cancer must be excluded. Refer under 2-week wait pathway.
"HPV is Necessary, Not Sufficient": Nearly all cervical cancers are caused by HPV, but most HPV infections clear spontaneously. Persistent high-risk HPV with other risk factors leads to malignancy.
"Primary HPV Screening": UK cervical screening now tests for HPV first. Only HPV-positive samples undergo cytology. This is more sensitive than cytology-first.
"Gardasil 9 = Game Changer": The 9-valent HPV vaccine protects against types 16, 18, 6, 11, 31, 33, 45, 52, 58 — covering ~90% of cervical cancers. Vaccination before sexual debut is most effective.
"FIGO 2018 = Imaging Allowed": The 2018 FIGO staging update allows imaging (MRI, CT, PET) to inform staging. Previously staging was purely clinical. This improves accuracy for treatment planning.
Why This Matters Clinically
Cervical cancer is one of the most preventable cancers when detected and treated at the pre-invasive stage. Every clinician should understand the cervical screening programme, recognise red flag symptoms requiring urgent referral, and appreciate the role of HPV vaccination in primary prevention. In developing countries without screening, cervical cancer remains a leading cause of cancer death.[1,2]
Incidence & Prevalence
| Parameter | Data |
|---|---|
| Global incidence | ~604,000 new cases/year (2020); 4th most common cancer in women |
| Global mortality | ~342,000 deaths/year |
| UK incidence | ~3,200 new cases/year |
| UK mortality | ~850 deaths/year |
| Peak age | 30-34 years (incidence); 85-89 (mortality peak) |
Demographics
| Factor | Details |
|---|---|
| Age distribution | Bimodal: Peak 30-45, second peak >65 (often missed screening) |
| Geographic variation | Highest rates in sub-Saharan Africa, South America (limited screening) |
| UK trend | Declining due to screening and vaccination (but recent concerns about COVID-related delays) |
Risk Factors
| Factor | Relative Risk | Notes |
|---|---|---|
| Persistent high-risk HPV | Essential cause | Types 16, 18 cause 70% of cases |
| Early age first intercourse | 2x | Immature cervix more susceptible |
| Multiple sexual partners | 3x | Increased HPV exposure |
| Smoking | 2x | Carcinogens concentrate in cervical mucus |
| HIV/Immunosuppression | 5x | Impaired HPV clearance |
| COCP use >5 years | 1.5-2x | Mechanism unclear; risk falls after stopping |
| High parity | 1.5x | Cervical trauma; hormonal factors |
| Low socioeconomic status | Variable | Reduced screening uptake |
| Non-attendance for screening | High | Most cervical cancers occur in unscreened women |
Mechanism of Carcinogenesis
Step 1: HPV Infection
- Sexual transmission of HPV (usually years before cancer)
- High-risk types: 16, 18, 31, 33, 45, 52, 58
- 80% of sexually active women infected at some point
- Most infections clear within 1-2 years
Step 2: Persistence and Integration
- ~10% of infections persist
- HPV genome integrates into host DNA
- E6 and E7 oncoproteins expressed continuously
- E6 → degrades p53 tumour suppressor
- E7 → inactivates Rb tumour suppressor
Step 3: Dysplasia (CIN)
- Uncontrolled cell proliferation in epithelium
- CIN1: Mild dysplasia, lower third of epithelium
- CIN2: Moderate dysplasia, two-thirds
- CIN3: Severe dysplasia/carcinoma in situ, full thickness
- CIN1 often regresses; CIN2/3 may progress to invasive cancer
Step 4: Invasive Carcinoma
- Breach of basement membrane
- Local invasion into cervical stroma
- Spread to parametrium, vagina, bladder, rectum
- Lymphatic spread to pelvic and para-aortic nodes
- Haematogenous spread rare until late (lung, liver, bone)
Histological Types
| Type | Proportion | Features |
|---|---|---|
| Squamous cell carcinoma | 70-80% | From ectocervix; most related to HPV 16 |
| Adenocarcinoma | 15-20% | From endocervical glands; HPV 18/16; may be harder to detect on screening |
| Adenosquamous | 3-5% | Mixed; aggressive |
| Small cell/neuroendocrine | <3% | Very aggressive; poor prognosis |
FIGO Staging (2018)
| Stage | Description | Treatment Approach |
|---|---|---|
| IA | Microscopic disease only (IA1 ≤3mm depth; IA2 3-5mm) | Conisation or simple hysterectomy |
| IB | Clinically visible tumour confined to cervix (IB1 <2cm; IB2 2-4cm; IB3 ≥4cm) | Radical hysterectomy or chemoradiotherapy |
| IIA | Upper 2/3 vagina, no parametrial invasion | Chemoradiotherapy or radical surgery |
| IIB | Parametrial invasion | Chemoradiotherapy |
| IIIA | Lower 1/3 vagina | Chemoradiotherapy |
| IIIB | Pelvic sidewall; hydronephrosis | Chemoradiotherapy |
| IIIC | Pelvic (IIIC1) or para-aortic (IIIC2) lymph node involvement | Chemoradiotherapy |
| IVA | Bladder or rectal mucosa invasion | Chemoradiotherapy ± pelvic exenteration |
| IVB | Distant metastases | Palliative chemotherapy |
Symptoms
| Symptom | Notes |
|---|---|
| Post-coital bleeding (PCB) | Most common presenting symptom; always investigate |
| Intermenstrual bleeding (IMB) | Vaginal bleeding between periods |
| Post-menopausal bleeding (PMB) | Any vaginal bleeding after menopause |
| Abnormal vaginal discharge | Watery, blood-stained, or offensive |
| Pelvic pain | Suggests advanced disease |
| Leg oedema | Lymphatic obstruction |
| Dysuria/haematuria | Bladder invasion |
| Rectal bleeding/tenesmus | Rectal invasion |
Signs
| Finding | Significance |
|---|---|
| Abnormal cervix on speculum | Visible tumour, ulceration, friable lesion |
| Contact bleeding | Tumour bleeds on touch |
| Fixed pelvis on examination | Parametrial invasion |
| Leg lymphoedema | Advanced pelvic disease |
| Renal mass | Hydronephrosis from ureteric obstruction |
Red Flags
[!CAUTION] Red Flags — Urgent 2WW Referral:
- Post-coital bleeding at any age
- Unexplained intermenstrual bleeding (>40 years or persistent)
- Visible cervical abnormality on examination
- Post-menopausal bleeding
- Offensive vaginal discharge with bleeding
Speculum Examination
Key Findings:
- Abnormal appearance: Ulceration, mass, friability
- Contact bleeding (bleeds on touch)
- Cervical distortion or barrel-shaped cervix
- Extension to vaginal fornices
When to Refer:
- Any visible abnormality on cervix → Urgent 2WW
- Abnormal screening result → Colposcopy referral
- Symptoms but normal-appearing cervix → Still refer if persistent
Bimanual Examination
Assessment:
- Cervical size and consistency
- Uterine size and mobility
- Parametrial involvement (induration, nodularity)
- Pelvic masses
- Fixation to pelvic sidewall (advanced disease)
Rectal Examination
- Assess parametrial spread posteriorly
- Rectovaginal involvement
- Complete staging examination (EUA)
First-Line Investigations
| Investigation | Purpose | Expected Findings |
|---|---|---|
| Cervical smear + HPV test | Screening pathway | HPV positive + High-grade dyskaryosis |
| Colposcopy + Biopsy | Diagnostic | Histological confirmation of CIN or invasive carcinoma |
| FBC, U&E, LFTs | Baseline | Anaemia (bleeding); renal function (hydronephrosis) |
Staging Investigations
| Investigation | Purpose |
|---|---|
| MRI Pelvis | Gold standard for local staging; parametrial invasion, tumour size |
| CT Chest/Abdomen/Pelvis | Distant metastases; lymph node assessment |
| PET-CT | Nodal disease; occult metastases; treatment planning |
| Cystoscopy/Sigmoidoscopy | If bladder or rectal involvement suspected |
| Examination Under Anaesthesia (EUA) | Full clinical staging before treatment decision |
Colposcopy Findings
| Finding | Interpretation |
|---|---|
| Acetowhite changes | Abnormal cells turn white with acetic acid |
| Punctation | Abnormal vessel pattern (stippled) |
| Mosaicism | Tile-like vascular pattern |
| Atypical vessels | Irregular, branching — suggests invasion |
| Lugol's negative | Non-glycogen containing (abnormal) cells don't stain brown |
Management Algorithm
CERVICAL CANCER MANAGEMENT
↓
┌────────────────────────────────────────────────────────────────┐
│ STAGING (FIGO 2018) │
├────────────────────────────────────────────────────────────────┤
│ ➤ Clinical examination (EUA) │
│ ➤ MRI pelvis (local staging) │
│ ➤ CT CAP or PET-CT (nodal and distant staging) │
│ ➤ Multidisciplinary Team (MDT) discussion │
└────────────────────────────────────────────────────────────────┘
↓
┌────────────────────────────────────────────────────────────────┐
│ TREATMENT BY STAGE │
├────────────────────────────────────────────────────────────────┤
│ STAGE IA1 (microscopic, <3mm, no LVSI): │
│ ➤ LLETZ or cone biopsy (fertility preserving) │
│ ➤ Simple hysterectomy if family complete │
├────────────────────────────────────────────────────────────────┤
│ STAGE IA2, IB1 (<2cm): │
│ ➤ Radical trachelectomy (fertility preserving) OR │
│ ➤ Radical hysterectomy + pelvic lymphadenectomy │
├────────────────────────────────────────────────────────────────┤
│ STAGE IB2-IIA (2-4cm, upper vagina): │
│ ➤ Radical hysterectomy + pelvic lymphadenectomy OR │
│ ➤ Concurrent chemoradiotherapy (CCRT) │
│ ➤ (Either option — similar outcomes) │
├────────────────────────────────────────────────────────────────┤
│ STAGE IIB-IVA (parametrium, pelvic wall, bladder/rectum): │
│ ➤ Concurrent chemoradiotherapy (CCRT) │
│ ➤ Cisplatin weekly + external beam RT + brachytherapy │
│ ➤ No role for primary surgery │
├────────────────────────────────────────────────────────────────┤
│ STAGE IVB (distant metastases): │
│ ➤ Palliative chemotherapy │
│ ➤ Platinum-based ± bevacizumab │
│ ➤ Immunotherapy (pembrolizumab) for PD-L1 positive │
│ ➤ Supportive/palliative care │
└────────────────────────────────────────────────────────────────┘
Surgical Options
| Procedure | Indication | Description |
|---|---|---|
| LLETZ (Loop Excision) | CIN; IA1 without LVSI | Loop electrosurgical excision of transformation zone |
| Cone Biopsy | IA1; fertility preservation | Conical excision of cervix |
| Radical Trachelectomy | IA2-IB1 (<2cm), fertility desired | Removal of cervix + parametrium; uterus preserved |
| Radical Hysterectomy (Wertheim's) | IB-IIA | Uterus + cervix + parametrium + upper vagina + pelvic lymph nodes |
| Pelvic Exenteration | Central recurrence; IVA select | Removal of bladder/rectum ± reproductive organs |
Chemoradiotherapy
| Component | Details |
|---|---|
| Chemotherapy | Cisplatin 40 mg/m² weekly during radiotherapy (radiosensitiser) |
| External Beam Radiotherapy | 45-50 Gy in 25 fractions to pelvis (± para-aortic nodes) |
| Brachytherapy | High-dose rate intracavitary brachytherapy (boost to tumour) |
| Duration | Total treatment 5-8 weeks; avoid prolongation (decreases efficacy) |
Treatment Complications
| Treatment | Complications |
|---|---|
| Surgery | Bladder/ureteric injury, lymphocyst, VTE, sexual dysfunction, lymphoedema |
| Radiotherapy | Acute: Diarrhoea, cystitis, skin reaction. Late: Vaginal stenosis, bowel/bladder fistula, rectal/bladder bleeding |
| Chemotherapy | Nausea, nephrotoxicity (cisplatin), myelosuppression |
Disease Complications
| Complication | Management |
|---|---|
| Ureteric obstruction/hydronephrosis | Nephrostomy or ureteric stent |
| Fistulae (vesicovaginal, rectovaginal) | Surgical repair; palliative management |
| Recurrent disease | Exenteration if central recurrence; chemo/immunotherapy if disseminated |
| Lymphoedema | Compression; physiotherapy; management of infections |
| Psychological | Counselling; support groups |
Survival by Stage
| FIGO Stage | 5-Year Survival |
|---|---|
| IA | 95-100% |
| IB | 80-90% |
| IIA | 70-80% |
| IIB | 60-70% |
| IIIA-IIIB | 30-50% |
| IVA | 15-25% |
| IVB | <20% |
Prognostic Factors
| Good Prognosis | Poor Prognosis |
|---|---|
| Early stage (IA-IB) | Advanced stage (IIIB-IV) |
| Squamous histology | Adenocarcinoma (slightly worse); neuroendocrine (very poor) |
| Node negative | Lymph node involvement |
| Small tumour | Large tumour (>4cm) |
| No lymphovascular invasion | LVSI present |
Key Guidelines
| Guideline | Organisation | Year | Key Points |
|---|---|---|---|
| Cervical Cancer Management | NICE | 2022 | Referral pathways, staging, treatment |
| FIGO Staging | FIGO | 2018 | Allows imaging for staging |
| Cervical Screening Programme | NHS CSP | Ongoing | HPV primary testing; intervals; colposcopy criteria |
Landmark Studies
Green et al. GOG 120 (1999) — Concurrent Chemoradiotherapy
- Showed cisplatin-based chemoradiotherapy improved survival vs RT alone
- Established CCRT as standard for locally advanced cervical cancer
- PMID: 10379956
LACC Trial (Ramirez et al. 2018)
- Compared minimally invasive surgery (MIS) vs open radical hysterectomy
- MIS associated with worse disease-free survival and overall survival
- Changed practice: Open surgery now preferred
- PMID: 30380365
HPV Vaccination Efficacy (Arbyn et al. 2018 Cochrane)
- Vaccine highly effective against HPV 16/18-related precancerous lesions
- Near elimination of CIN2+ in vaccinated populations
- PMID: 29740819
Evidence Strength
| Intervention | Level | Evidence |
|---|---|---|
| Concurrent chemoradiotherapy | 1a | RCTs, meta-analyses |
| HPV vaccination | 1a | RCTs, real-world data |
| Open radical hysterectomy | 1b | LACC trial |
| Primary HPV screening | 1b | RCTs |
What is Cervical Cancer?
Cervical cancer is a cancer that develops in the cervix — the lower part of the womb that opens into the vagina. It is one of the few cancers that can be largely prevented through vaccination and regular screening.
What causes it?
Most cervical cancers are caused by persistent infection with human papillomavirus (HPV) — a very common virus. HPV is spread through sexual contact, and most people clear the infection naturally. In some cases, the virus persists and causes changes to cervical cells that can become cancer over many years.
How can I protect myself?
- HPV vaccination: Offered to all children aged 12-13 in the UK; protects against the HPV types that cause most cervical cancers
- Cervical screening (smear test): Detects cell changes early, before cancer develops
- Attend your screening appointments: The programme invites women aged 25-64
What are the symptoms?
Early cervical cancer often has no symptoms. Symptoms to look out for include:
- Bleeding after sex
- Bleeding between periods or after menopause
- Unusual vaginal discharge
- Pain during sex
How is it treated?
Treatment depends on the stage:
- Very early: A small procedure to remove abnormal cells (LLETZ)
- Early cancer: Surgery to remove the cervix or womb
- Advanced: Chemotherapy and radiotherapy combined
When caught early, cervical cancer has an excellent cure rate.
When to seek help
See your GP if you have any symptoms listed above, even if you're up to date with screening. Don't wait for your next screening appointment — symptoms should always be checked.
Guidelines
-
National Institute for Health and Care Excellence (NICE). Cervical cancer: recognition and referral (NG12). 2015 (updated 2022). nice.org.uk
-
FIGO Committee on Gynecologic Oncology. FIGO staging for carcinoma of the vulva, cervix, and corpus uteri. Int J Gynaecol Obstet. 2019;145(1):129-135. PMID: 30656645
Key Trials
-
Green JA, Kirwan JM, Tierney JF, et al. Survival and recurrence after concomitant chemotherapy and radiotherapy for cancer of the uterine cervix: a systematic review and meta-analysis. Lancet. 2001;358(9284):781-786. PMID: 11564482
-
Ramirez PT, Frumovitz M, Pareja R, et al. Minimally Invasive versus Abdominal Radical Hysterectomy for Cervical Cancer. N Engl J Med. 2018;379(20):1895-1904. PMID: 30380365
-
Arbyn M, Xu L, Simoens C, Martin-Hirsch PP. Prophylactic vaccination against human papillomaviruses to prevent cervical cancer and its precursors. Cochrane Database Syst Rev. 2018;5(5):CD009069. PMID: 29740819
Reviews
-
Bhatla N, Aoki D, Sharma DN, Sankaranarayanan R. Cancer of the cervix uteri: 2021 update. Int J Gynaecol Obstet. 2021;155 Suppl 1(Suppl 1):28-44. PMID: 34669203
-
Jo's Cervical Cancer Trust. Patient information. jostrust.org.uk
High-Yield Exam Topics
| Topic | Key Points |
|---|---|
| HPV role | High-risk types (16, 18); E6/E7 oncoproteins; degrades p53 and Rb |
| Screening | HPV primary testing → cytology if positive → colposcopy if abnormal |
| CIN | Cervical Intraepithelial Neoplasia grades 1-3; CIN3 = carcinoma in situ |
| FIGO staging | 2018 update allows imaging; Stage IIIC = nodal involvement |
| Treatment | Early = surgery; IIB+ = chemoradiotherapy; no combined modality |
| LACC trial | Open surgery > minimally invasive for radical hysterectomy |
Sample Viva Questions
Q1: A 32-year-old presents with post-coital bleeding. How do you manage her?
Model Answer: Post-coital bleeding requires urgent investigation to exclude cervical cancer. I would take a history (bleeding pattern, contraception, last smear, sexual history), perform speculum examination (to visualise the cervix), take an STI screen (Chlamydia can cause cervical inflammation), and ensure her cervical screening is up to date. If the cervix looks abnormal, I would refer urgently under the 2-week wait pathway. If the cervix appears normal but symptoms persist, I would still refer for colposcopy. Common benign causes include ectropion and cervicitis, but cervical cancer must be excluded.
Q2: What is the role of concurrent chemoradiotherapy in cervical cancer?
Model Answer: Concurrent chemoradiotherapy (CCRT) using weekly cisplatin with external beam radiotherapy plus brachytherapy is the standard treatment for locally advanced cervical cancer (Stage IIB-IVA). The landmark GOG 120 and other trials showed survival benefit of adding chemotherapy to radiotherapy. Cisplatin acts as a radiosensitiser, enhancing tumour cell kill. The regimen typically includes 45-50 Gy external beam RT with cisplatin 40 mg/m² weekly for 5-6 weeks, followed by brachytherapy boost. Treatment duration should not exceed 8 weeks as prolongation reduces efficacy.
Q3: What are the key findings from the LACC trial?
Model Answer: The LACC trial (Ramirez et al. 2018, NEJM) compared minimally invasive surgery (MIS) with open radical hysterectomy for early-stage cervical cancer. Unexpectedly, it found that MIS was associated with worse disease-free survival (86% vs 96.5%) and overall survival compared to open surgery. This led to a significant change in practice — open (abdominal) radical hysterectomy is now the preferred approach for cervical cancer surgery. The trial highlighted that oncological outcomes may differ between surgical modalities even when procedural steps are similar.
Common Exam Errors
| Error | Correct Approach |
|---|---|
| Forgetting HPV role | Nearly all cervical cancer is caused by HPV (16, 18 = 70%) |
| Confusing screening with diagnostic | Screening = asymptomatic; symptomatic women need investigation regardless of screening |
| Recommending combined surgery + radiotherapy | Avoid: gives toxicity without benefit; choose one modality |
| Missing LACC trial implications | Open surgery preferred over MIS for radical hysterectomy |
| Forgetting vaccination | HPV vaccine prevents majority of cervical cancers |
Last Reviewed: 2025-12-24 | MedVellum Editorial Team
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.