Conditions - Cervical Cancer & Intraepithelial Neoplasia

Question 1

What are the definitions of cervical cancer and cervical intraepithelial neoplasia (CIN)?

Answer 1

Cervical cancer – cancer of the cervix

CIN – cervical intraepithelial neoplasia – the abnormal growth of cells on the surface of the cervix that could potentially lead to cervical cancer.

Question 2

What is the aetiology of cervical cancer and what are its risk factors?

Answer 2

Main cause is HPV – detected in 99% of cervical cancer – serotypes 16, 18, 33

Risk factors

• Exposure to HPV
• Impaired immune response to HPV infection (inability to clear the virus) (HIV)
• Smoking
• Early first intercourse/many sexual partners
• High parity
• Low socioeconomic status
• Combined OCP

Mechanism of cause

• HPV 16 & 18 produce oncogenes E6 and E7 respectively
• E6 inhibits p53 tumour suppressor gene
• E7 inhibits RB suppressor gene

Almost all cases originate from the ecto-endocervical mucosa in the ‘transformation zone’ (area between old and new squamocolumnar junction)

Question 3

What is the epidemiology of cervical cancer?

Answer 3

Can develop at any age but CIN1 4%, CIN 5% (in US)

50% of cases occur in women under 45, incidence highest amongst 25-29 years

• Squamous cell carcinoma 80%
• Adenocarcinoma 20%

Question 4

What are the presenting symptoms of cervical cancer?

Answer 4

• Abnormal vaginal bleeding: postcoital, intermenstrual, or postmenopausal bleeding
• Vaginal discharge (can contain dead material, can be multiple colours and foul-smelling)
• Pelvic pain
• Dyspareunia

Question 5

What are the signs of cervical cancer on physical exam?

Answer 5

Abnormal appearance of the cervix on examination with speculum

Question 6

What are the appropriate investigations for cervical cancer and what results suggest it?

Answer 6

Urgent cancer referral for colposcopy

• Ulceration
• Inflammation
• Bleeding
• Visible tumour

Question 7

What is the management plan for cervical cancer?

Answer 7

Urgent 2 week referral for colposcopy or gynaecological oncology (all women with unexplained postmenopausal bleeding should be referred this way)

Punch or excisional biopsy of suspicious lesions (LLETZ or cone biopsy) to test for malignancy

Staging – uses clinical, radiological, or pathological findings to direct specialist treatment plan (1-4)

Depends on stage

• CIN – colposcopy then if moderate/severe abnormalities excise or ablate the region with LLETZ. Test of cure 6mo later with smear test. Can offer simple hysterectomy if woman isn’t bothered about fertility.
• IA1 (microinvasive) – conservative approach (LLETZ or cone biopsy)
• IA2-IIA (early) - <4cm = radical hysterectomy + lymphadenectomy. >4 cm = add chemoradiation
• IIB-IVA (locally advanced) – chemoradiation with external beam or brachytherapy and cisplatin (improves cure rates)
• IVB (metastatic) – systemic/combination chemotherapy (alt single agent therapy palliative care)

If pregnant – MDT approach + delivery post-35w

Recurrent – surgery, palliative chemo, supportive care

Question 8

What are the complications of cervical cancer and how are they managed?

Answer 8

Complications almost all due to treatment complications

• LLETZ – increased risk of midtrimester miscarriage and preterm delivery
• Radical hysterectomy – bladder dysfunction (intermittent self-catheterisation), sexual dysfunction (reduced libido, vaginal dryness, dyspareunia) due to vaginal shortening, lymphoedema (leg elevation, skin care, massage)
• Radiotherapy – early (radiotherapy-induced) menopause and loss of fertility, lethargy, bowel and bladder urgency, skin erythema. Long-term – fibrosis, vaginal stenosis, cystitis-like symptoms, malabsorption and mucous diarrhoea

Question 9

What is the prognosis of cervical cancer?

Answer 9

Early detection vital with 5-year survival 98% at stage 1A down to 15% at stage 4.