Cervical cancer and HPV
Exam Tips
- In OSCEs, persistent postcoital/intermenstrual bleeding with a friable cervix is a red-flag pattern needing urgent suspected-cancer referral.
- Most HPV infections clear spontaneously; persistence (same HPV type on repeat testing) is the key biological step toward CIN2/3 and cancer.
- Know the transformation zone as the main site of malignant change and screening sampling target.
- State that HPV vaccination is preventive, not a treatment for established cervical cancer.
- For prognosis questions, anchor your answer to FIGO stage and nodal status, then cite markedly better outcomes in stage I than stage IV.
Definition
Cervical cancer is a malignant tumour arising from cervical epithelium, most often in the transformation zone between squamous and columnar mucosa. In UK practice it is strongly linked to persistent high-risk HPV infection and is frequently preceded by cervical intraepithelial neoplasia (especially CIN2/3), with progression to invasive disease after breach of the basement membrane.
Pathophysiology
High-risk HPV (especially types 16 and 18, with 31/33/45/52/58 also important) infects basal cervical epithelial cells at the transformation zone. Most infections clear within 2 years, but persistent type-specific infection (detectable again at 6-12 months) drives viral oncoprotein effects (classically E6/E7-mediated disruption of tumour suppressor pathways), causing progression from CIN1 to CIN2/3 and eventually invasive carcinoma over years to decades. Squamous cell carcinoma is most common, with adenocarcinoma the next major subtype. See Figure: transformation zone and squamocolumnar junction anatomy in FIGO cervical cancer report (Bhatla, 2021).
Risk Factors
- Persistent high-risk HPV infection
- Early sexual debut
- Multiple sexual partners or partner with high-risk sexual history
- Past sexually transmitted infection
- Limited condom/barrier use
- Immunosuppression (for example HIV infection, post-transplant immunosuppression)
- Smoking
- Long-term combined oral contraceptive use (>5 years)
- High parity (>5 full-term births) and first birth at young age
- First-degree family history of cervical cancer
- Previous HPV-related vulval or vaginal dysplasia
Clinical Features
Symptoms
- Persistent intermenstrual bleeding
- Postcoital bleeding
- Postmenopausal bleeding
- Persistent unexplained vaginal discharge (may be blood-stained or offensive)
- Pelvic pain
- Dyspareunia
- Advanced disease symptoms: weight loss, fatigue, back/pelvic/loin pain, haematuria, urinary or bowel disturbance
Signs
- Cervix may appear friable, inflamed, irregular, ulcerative, necrotic, or bleed on contact
- Visible cervical mass/lesion on speculum examination
- Pelvic sidewall tenderness/fixed disease in advanced cases
- Lower-limb oedema or supraclavicular/para-aortic lymphadenopathy in metastatic spread
- Features of fistulae in advanced disease (continuous urinary or faecal leakage per vagina)
Investigations
Management
Lifestyle Modifications
- Encourage smoking cessation to reduce persistence/progression risk
- Promote attendance for cervical screening and follow-up appointments
- Offer/complete HPV vaccination where eligible (including catch-up cohorts)
- Advise condom use to reduce HPV transmission and other STI co-factors
- Address psychosexual and fertility concerns early; involve specialist support services
Pharmacological Treatment
HPV immunization (prevention)
- Human papillomavirus vaccine (Gardasil 9) 0.5 mL IM per dose; usually 2-dose schedule (0 and 6-24 months) in younger adolescents, with 3-dose schedule (0, 2, 6 months) in some older or immunocompromised groups
Prophylactic, not therapeutic for existing cervical cancer. Contraindicated in previous anaphylaxis to vaccine components (including yeast in Gardasil 9). Defer in acute severe febrile illness.
Concurrent chemoradiotherapy for locally advanced disease
- Cisplatin 40 mg/m2 IV once weekly during external beam radiotherapy (typically 5-6 cycles)
Specialist oncology regimen. Major safety issues: nephrotoxicity, ototoxicity, peripheral neuropathy, severe nausea/vomiting, myelosuppression; avoid or modify in significant renal impairment and ensure hydration/antiemetic prophylaxis.
Systemic therapy for recurrent/metastatic disease
- Paclitaxel 175 mg/m2 IV every 3 weeks plus cisplatin 50 mg/m2 IV every 3 weeks
- Paclitaxel 175 mg/m2 IV every 3 weeks plus carboplatin (AUC 5) every 3 weeks
- Bevacizumab 15 mg/kg IV every 3 weeks (selected patients, usually with platinum-taxane chemotherapy)
- Pembrolizumab 200 mg IV every 3 weeks or 400 mg every 6 weeks (selected biomarker-defined patients, usually in combination regimens)
Use only in specialist MDT pathways. Key cautions: marrow suppression/infection risk, thromboembolism and bleeding risks, hypertension/proteinuria/GI perforation with bevacizumab, immune-related toxicities with checkpoint inhibitors; strict pregnancy avoidance and fertility counselling required.
Surgical / Interventional
- Excisional treatment of high-grade pre-invasive disease (LLETZ/cone biopsy)
- Fertility-sparing radical trachelectomy in selected early-stage disease
- Radical hysterectomy with pelvic lymph node assessment/dissection for appropriate early-stage cancers
- Definitive chemoradiotherapy with brachytherapy for many locally advanced tumours
- Pelvic exenteration in carefully selected central pelvic recurrence after prior treatment
Complications
- Psychological morbidity (anxiety, depression, fear of recurrence, reduced quality of life)
- Sexual dysfunction (loss of libido, dyspareunia, vaginal dryness/stenosis/shortening)
- Infertility and premature menopause after surgery or radiotherapy
- Bladder dysfunction (urgency, frequency, pain, urge incontinence, retention, haematuria)
- Bowel dysfunction (diarrhoea, urgency, faecal incontinence)
- Hydronephrosis/hydroureter leading to renal impairment or renal failure
- Severe pelvic haemorrhage in advanced/recurrent disease
- Vesicovaginal or rectovaginal fistulae
- Lymphoedema after nodal disease, lymphadenectomy, or pelvic radiotherapy
- Distant metastatic disease (lung, liver, bone) with pain and systemic decline
Prognosis
Prognosis is stage-dependent (FIGO stage and nodal status are key). UK survival is much better in early-stage disease (about 96% 1-year survival for stage I versus about 50% for stage IV), with overall survival around 81% at 1 year, 61% at 5 years, and 51% at 10 years. Untreated high-grade dysplasia carries substantial progression risk, while recurrence (often within 3 years) is associated with poorer outcomes.
Sources & References
🏥BMJ Best Practice(1)
💊BNF Drug References(2)
- Etonogestrel[cautions]
- Ulipristal acetate[contraindications]
✅NICE Guidelines(1)
- Cervical cancer and HPV[overview]