Cervical cancer

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Cervical cancer develops after persistent oncogenic HPV infection, usually through a detectable and treatable intraepithelial phase. Screening samples asymptomatic people; it does not diagnose a visible cancer. A normal previous HPV or cytology result reduces but does not eliminate risk, and postcoital or unexplained bleeding must prompt examination. Squamous carcinoma remains the commonest histology, with adenocarcinoma arising higher in the canal and sometimes escaping visual screening more readily.

Colposcopic biopsy establishes diagnosis. A cone excision can fully stage microscopic disease, reporting depth, horizontal extent, margins and lymphovascular invasion. MRI defines tumour and adjacent pelvic planes. PET-CT is valuable for nodal and distant staging before radical radiotherapy, while examination under anaesthesia, cystoscopy or proctoscopy are used when anatomy or suspected invasion requires direct assessment. Renal function and hydronephrosis influence both stage and cisplatin safety.

Treatment balances tumour size, nodes, fertility and combined-modality harm. Microscopic low-risk cancer may be cured by cone excision. Selected early disease undergoes trachelectomy or radical hysterectomy with nodal assessment. Locally advanced cancer is treated by external-beam radiation and weekly cisplatin followed by or integrated with brachytherapy. Delays and omission of brachytherapy reduce cure probability; supportive care should maintain the schedule safely.

Recurrent disease requires biopsy when feasible because radiation necrosis and infection can mimic tumour. Central relapse after previous radiation may be surgically salvageable in a highly selected patient, whereas metastatic disease uses biomarker- and prior-treatment-directed systemic therapy. Bleeding, renal obstruction, fistula, pain, lymphoedema and sexual and bowel effects often dominate quality of life and need specialist care alongside anticancer treatment.

Key points

Persistent high-risk HPV causes most cervical cancer; HPV vaccination and screening prevent disease but a symptomatic cervix always enters a diagnostic, not screening, pathway.
Key symptoms are postcoital, intermenstrual or postmenopausal bleeding, watery or offensive discharge, pelvic pain and dyspareunia; advanced disease causes leg oedema, renal obstruction and fistula.
First-line assessment is speculum and bimanual examination followed by urgent colposcopy and directed biopsy of a suspicious cervix; do not rely on cytology alone to exclude invasion.
The diagnostic reference standard is histology that defines squamous, adenocarcinoma or rarer type, depth and lymphovascular invasion where a cone specimen is used.
MRI pelvis is preferred for local tumour, parametrial, vaginal and pelvic-organ staging; PET-CT or contrast CT evaluates pelvic, para-aortic and distant disease for radical planning.
Very small stage IA1 squamous cancer without lymphovascular invasion may be treated by complete cone biopsy or simple hysterectomy, depending fertility and margin status.
Fertility-preserving radical trachelectomy with nodal staging is limited to carefully selected small early tumours and requires obstetric and recurrence counselling.
Early operable disease may undergo radical hysterectomy and nodal assessment; avoid combining radical surgery and full chemoradiation unnecessarily because morbidity accumulates.
First-line curative treatment for locally advanced cervical cancer is external-beam radiotherapy with weekly cisplatin and mandatory image-guided brachytherapy, usually completed without avoidable prolongation.
Brachytherapy is not an optional boost that external beam can routinely replace; overall treatment time and central dose are critical to local control.
Recurrent or metastatic therapy uses platinum–taxane combinations with immune, anti-VEGF or other treatment according to PD-L1, prior cisplatin, anatomy, fistula risk and current funding.
Relapse confined centrally after radiation may be considered for pelvic exenteration only after biopsy, complete staging and specialist resectability and rehabilitation review.
Offer fertility preservation, ovarian transposition, menopause and sexual-health support before treatment when time and disease anatomy allow.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Persistent high-risk HPV

Longstanding infection with oncogenic HPV, particularly types 16 and 18, is the necessary driver of most squamous and adenocarcinomas.

Impaired viral clearance

HIV, transplant immune suppression, smoking and other immune compromise increase persistence, high-grade intraepithelial disease and invasive-cancer risk.

Screening under-access

Non-attendance, inequitable access, trauma, disability and loss to follow-up after abnormal testing allow treatable precursor disease to progress.

Rare non-HPV pathways

Gastric-type adenocarcinoma, clear-cell disease associated historically with in-utero diethylstilbestrol and other rare histologies follow distinct biology.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Viral oncogenes disable checkpoints
HPV E6 and E7 proteins promote p53 and retinoblastoma pathway loss, permitting accumulation of genomic damage in transformation-zone cells.
2
Precursor disease breaches stroma
Persistent high-grade squamous or glandular intraepithelial neoplasia crosses the basement membrane and gains lymphovascular and stromal access.
3
Local extension threatens pelvic organs
Tumour spreads into parametrium, vagina, ureters, bladder, rectum and pelvic sidewall, causing bleeding, fistula, pain and renal obstruction.
4
Nodes follow pelvic chains
Spread proceeds through parametrial, obturator, internal and external iliac and para-aortic nodes before more distant lung, liver, bone and supraclavicular disease.
5
Radiation requires intracavitary dose
External-beam treatment controls pelvis and nodes, while image-guided brachytherapy delivers the curative high central dose without intolerable exposure to bladder and rectum.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Early symptomatic disease

Postcoital or intermenstrual bleeding, watery discharge and a friable irregular cervix can occur before pain or palpable parametrial disease.

Glandular or endocervical disease

Adenocarcinoma may sit higher in the canal with a barrel cervix or bleeding despite limited visible ectocervical abnormality.

Locally advanced disease

Parametrial fixation, lower-vaginal involvement, pelvic sidewall pain, hydronephrosis, haematuria or rectal symptoms indicates extension beyond an early surgical field.

Nodal or metastatic disease

Unilateral leg oedema, supraclavicular node, cough, bone pain or liver symptoms can reflect pelvic, para-aortic or distant spread.

Haemorrhage or sepsisRed flag

Brisk bleeding, shock, fever with necrotic discharge or obstructed infected uterus requires immediate resuscitation and specialist source control.

Post-treatment recurrence

New bleeding, pelvic pain, leg oedema, renal dysfunction or fistula after treatment requires prompt examination, imaging and planned biopsy.

Red flags requiring action

Persistent postcoital, intermenstrual or postmenopausal bleeding needs direct cervical examination even when the last screening test was negative.
A visible irregular, ulcerated or friable cervix requires urgent colposcopy and biopsy rather than a screening sample alone.
Heavy bleeding with syncope, tachycardia, hypotension or falling haemoglobin requires immediate haemostatic and transfusion support.
Flank pain, oliguria, rising creatinine or bilateral hydronephrosis suggests ureteric obstruction from parametrial or nodal disease.
Malodorous discharge, fever, pelvic pain and systemic illness can indicate infected tumour, pyometra or fistula with sepsis.
Leg oedema, sciatic pain, haematuria, rectal bleeding or pelvic sidewall fixation suggests advanced local or nodal involvement.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
First-line speculum and bimanual examinationFirst stepFirst line
Why
Identify a visible cervical lesion, bleeding source, vaginal extension, uterine and parametrial abnormality and infection.
Interpretation and limitations
A suspicious cervix needs urgent colposcopy and biopsy regardless of screening history; do not perform forceful examination during uncontrolled haemorrhage.
02
Reference colposcopic biopsy or diagnostic cone
Why
Confirm invasive histology and, for microscopic disease, define depth, width, margins and lymphovascular invasion.
Interpretation and limitations
Ablative treatment is inappropriate without histology, and an inadequate superficial biopsy must be repeated when invasion remains suspected.
03
Preferred MRI pelvisPreferred
Why
Stage tumour size, stromal and parametrial invasion, vagina, bladder, rectum and pelvic nodes and plan surgery or brachytherapy.
Interpretation and limitations
Correlate with clinical examination; post-biopsy inflammation can alter appearances and microscopic nodal disease may be radiologically occult.
04
PET-CT or contrast CT staging
Why
Assess pelvic and para-aortic nodes and lung, liver, bone and other distant sites before radical or recurrent treatment.
Interpretation and limitations
PET-avid nodes can be inflammatory, but confirmation is balanced against whether biopsy delay or risk would compromise a time-sensitive radical plan.
05
Renal and urinary assessment
Why
Detect hydronephrosis, infection and impaired filtration and establish fitness for cisplatin and contrast.
Interpretation and limitations
Use renal profile and ultrasound or CT; urgent stent or nephrostomy can restore function and treat sepsis before chemoradiation.
06
Predictive and inherited-risk tests
Why
Assess PD-L1 and other current biomarkers in advanced disease and HIV status where clinically appropriate.
Interpretation and limitations
Use validated scoring for a defined treatment indication and maintain screening and vaccination care for related anogenital HPV disease.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Cervical ectropion or polyp

Benign glandular eversion and polyps can bleed on contact, but suspicious, persistent or atypical tissue requires colposcopic assessment and histology.

Cervicitis and pelvic infection

Chlamydia, gonorrhoea and other infection cause discharge and contact bleeding; infection testing does not replace biopsy of an abnormal cervix.

Endometrial or vaginal cancer

Bleeding may arise above or below cervix, so speculum, bimanual and endometrial assessment are combined when the source remains uncertain.

Pregnancy-related change

Ectropion and decidual change can look vascular or irregular, but suspected cancer requires specialist colposcopy and pregnancy-adapted biopsy and imaging.

Radiation change or recurrence

After treatment, friability, stenosis and necrosis may mimic recurrent cancer; examination, imaging and carefully planned biopsy distinguish them.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01Abnormal bleedingExamine and biopsy the cervixFirst stepPostcoital, intermenstrual or postmenopausal bleeding or abnormal discharge persists.

1Take pregnancy, contraception, screening, infection and bleeding history and perform speculum and bimanual examination, stabilising major haemorrhage first.
2Refer a suspicious cervix directly for urgent colposcopy and biopsy rather than repeating screening cytology as the sole response.
3Once invasion is confirmed, obtain MRI and nodal or distant staging and refer to the specialist gynaecological oncology MDT with renal, fertility and anaesthetic assessment.

02Early stageSelect fertility-preserving or radical surgeryCone histology or imaging shows small disease confined to cervix without nodal or parametrial spread.

1Review exact depth, size, histology, lymphovascular invasion, margins, nodes and fertility goals with expert pathology and imaging.
2Use complete cone or simple hysterectomy for qualifying microscopic disease and trachelectomy or radical hysterectomy with sentinel or nodal staging for selected larger early disease.
3Review final margins, nodes and parametria before adjuvant treatment and avoid unnecessary full radiation after radical surgery when risk does not justify combined toxicity.

03Locally advancedComplete chemoradiation with brachytherapyDefinitiveTumour extends beyond an early surgical field or nodal and margin risk favours definitive radiation.

1Obtain PET-CT or CT, MRI and renal assessment, drain an obstructed infected system and plan external-beam pelvic and nodal fields and image-guided brachytherapy together.
2Give weekly cisplatin during external-beam radiation when renal and functional status permit, managing marrow, nausea, diarrhoea, urinary and skin toxicity proactively.
3Deliver brachytherapy and complete the total course within the recommended overall time, adapting intracavitary and interstitial technique to residual anatomy.

04Recurrent or metastaticBiopsy, biomarker test and control pelvic morbidityCancer persists, recurs after radical treatment or presents with distant metastasis.

1Confirm viable tumour when feasible, restage fully and assess prior radiation, fistula, renal function, PD-L1, symptoms, performance and treatment-free interval.
2Consider exenteration or focused radiation for highly selected local disease and choose funded platinum–taxane, immune or anti-VEGF systemic treatment for unresectable or metastatic disease.
3Treat bleeding, obstruction, fistula, infection, pain and lymphoedema concurrently and define response, stopping and emergency plans with early palliative care.

Key medicines and prescribing safety3 treatments · regimens, roles and cautions

Radiosensitises locally advanced cervical squamous and adenocarcinoma and improves cure when delivered with definitive pelvic radiation and brachytherapy.

Cisplatin radiosensitisation

Give cisplatin 40 mg/m² intravenously once weekly during external-beam radiotherapy, commonly for five or six doses and often capped at 70 mg per dose, using the exact local hydration and eligibility protocol.

Check creatinine clearance, magnesium, hearing, neuropathy, marrow and hydration before each dose; use an alternative plan for significant renal dysfunction and do not delay brachytherapy merely to complete chemotherapy.

Provides PD-1 blockade for selected persistent, recurrent or metastatic cervical cancer and may prolong control when the predictive criteria are met.

Pembrolizumab for eligible advanced disease

Give pembrolizumab 200 mg intravenously every 3 weeks or 400 mg every 6 weeks, with protocol chemotherapy or alone only within the licensed PD-L1, line and current NICE-funded cervical-cancer indication.

Assess autoimmune and transplant context and monitor for immune lung, bowel, liver, endocrine, renal, cardiac, skin and neurological toxicity; evaluate infection and progression simultaneously.

Inhibits VEGF-mediated angiogenesis and can improve disease control with systemic chemotherapy in suitable advanced disease.

Bevacizumab with selected systemic therapy

Give bevacizumab 15 mg/kg intravenously every 3 weeks with the licensed chemotherapy combination in eligible recurrent or metastatic cervical cancer under current funding criteria.

Avoid or use extreme caution with active major bleeding, uncontrolled hypertension, recent surgery, poor wound healing, perforation or fistula risk; monitor urine protein, thrombosis and blood pressure.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Haemorrhage and anaemia

Friable vascular tumour causes chronic iron loss or catastrophic bleeding requiring packing, embolisation, radiotherapy, transfusion and anticipatory crisis planning.

Ureteric obstruction and renal failure

Parametrial or nodal compression produces hydronephrosis, infection and impaired kidney function that can prevent cisplatin treatment unless decompressed.

Fistula and pelvic sepsis

Tumour or treatment can connect vagina with bladder or rectum, causing continuous leakage, infection, skin injury and profound social distress.

Nodal and distant metastasis

Pelvic and para-aortic nodes, lung, liver, bone and distant lymphatic spread cause oedema, pain, respiratory symptoms and organ failure.

Treatment-related pelvic dysfunction

Infertility, premature menopause, vaginal stenosis, bowel and bladder injury, lymphoedema, neuropathy and sexual dysfunction require long-term rehabilitation.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

During chemoradiation, review blood count, renal function, magnesium, weight, hydration, nausea, diarrhoea, urinary symptoms, pain and skin at least weekly.
Track total radiation and brachytherapy dates and intervene early on toxicity because avoidable prolongation can reduce local control.
After radical treatment, use structured clinical examination and symptom review, obtaining MRI or PET-CT for suspicious findings rather than routine screening cytology alone.
Monitor renal function and hydronephrosis, stent or nephrostomy infection and exchange needs during advanced pelvic disease.
Assess lower-limb lymphoedema, bowel and bladder function, pelvic pain, menopause, bone, vaginal stenosis and sexual health and offer pelvic-floor and dilator support.
During immune or anti-VEGF treatment, monitor organ toxicity, blood pressure, urine protein, bleeding, wound and fistula symptoms at each cycle.
Maintain cervical-screening and HPV-vaccination advice for eligible relatives and related lower-genital-tract surveillance for the patient according to anatomy and treatment.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Symptoms beat screening history

Screening reduces population risk but does not clear a friable cervix or persistent bleeding; diagnosis requires examination and tissue.

A cone can diagnose and cure

For truly microscopic low-risk disease, an intact adequately oriented excision provides depth and margins and may be definitive.

Hydronephrosis changes more than stage

Renal obstruction can prevent cisplatin and cause sepsis, so decompression may restore both safety and oncological options.

Brachytherapy supplies the central dose

External beam cannot routinely reproduce the steep conformal dose around cervix without unacceptable bladder and rectal exposure.

Combined radical modalities add harm

Planning surgery without regard to likely postoperative radiation can expose bladder, bowel, lymphatics and sexual function to both treatments.

Fistula risk influences systemic choice

Tumour invasion, previous radiation and anti-VEGF treatment interact, making careful anatomical review essential before bevacizumab.

11Common pitfallsFrequent interpretation and management errors.

01
Using a normal screening result to dismiss postcoital or postmenopausal bleeding.
02
Sending a cervical smear instead of urgent biopsy for a visibly suspicious cervix.
03
Ablating a lesion before invasive disease has been excluded histologically.
04
Selecting fertility-preserving surgery without exact size, histology, lymphovascular and nodal review.
05
Planning radical hysterectomy when postoperative chemoradiation is already highly likely and avoidable combined morbidity is substantial.
06
Replacing brachytherapy routinely with more external-beam dose.
07
Allowing manageable toxicity to cause prolonged gaps in a curative radiation course.
08
Giving cisplatin without renal, magnesium, hearing and hydration assessment.
09
Using bevacizumab without reviewing bleeding, wound, perforation and fistula risk.
10
Calling radiation necrosis recurrent cancer without planned imaging and tissue when feasible.