Cervical cancer

Cancer of the uterine cervix

Cancer of the uterine cervix is a malignant disease arising from the cervical epithelium and is strongly associated with persistent infection by high-risk types of human papillomavirus (HPV). It is one of the most common cancers affecting women, particularly in low- and middle-income countries. Cervical cancer is largely preventable through HPV vaccination, regular screening, early detection, and treatment of precancerous lesions. When diagnosed at an early stage, the disease is potentially curable through surgery or radiotherapy.

Epidemiology

Cervical cancer is among the leading causes of cancer-related morbidity and mortality among women worldwide. The burden is particularly high in regions with limited access to screening and HPV vaccination programs. Human immunodeficiency virus (HIV) infection significantly increases the risk of developing cervical cancer due to impaired immune clearance of HPV infection.

Risk factors

Risk factors for cervical cancer include:

• Persistent infection with high-risk HPV types.

• Early onset of sexual activity.

• Early childbirth.

• Multiple sexual partners.

• Smoking.

• HIV infection.

• Lack of regular cervical cancer screening.

• Absence of HPV vaccination.

Pathophysiology

Cervical cancer develops following persistent infection of cervical epithelial cells by oncogenic HPV strains. Persistent viral infection results in progressive cellular dysplasia and the development of precancerous lesions. Over time, untreated precancerous changes may progress to invasive carcinoma, which can spread locally to adjacent pelvic structures and eventually metastasize to distant organs.

Clinical presentation

The clinical presentation depends on the stage of the disease. Early-stage cervical cancer is often asymptomatic and may only be detected through routine screening. As the disease progresses, patients may develop abnormal vaginal bleeding, vaginal discharge, pelvic pain, and symptoms related to local invasion or distant spread.

Symptoms

Early disease

• Often asymptomatic.

Advanced disease

• Abnormal vaginal bleeding.

  • Post-coital bleeding.

  • Inter-menstrual bleeding.

  • Postmenopausal bleeding.

• Foul-smelling vaginal discharge.

• Pelvic pain.

• Urinary incontinence due to vesicovaginal fistula (VVF).

• Fecal incontinence due to rectovaginal fistula (RVF).

Clinical signs

Clinical findings may include:

• Visible cervical lesion.

• Friable cervical mass that bleeds on contact.

• Foul-smelling vaginal discharge.

• Pelvic mass.

• Evidence of local extension to surrounding tissues.

• Signs of fistula formation in advanced disease.

• Features of metastatic disease in late stages.

Differential diagnosis

Conditions that may present similarly include:

• Cervical polyps.

• Cervicitis.

• Cervical ectropion.

• Endometrial cancer.

• Vaginal cancer.

• Endometrial hyperplasia.

• Uterine fibroids associated with abnormal uterine bleeding.

• Pelvic inflammatory disease.

• Benign causes of postmenopausal bleeding.

Diagnostic criteria

A diagnosis of cervical cancer should be suspected in women presenting with:

• Post-coital bleeding.

• Inter-menstrual bleeding.

• Postmenopausal bleeding.

• Persistent foul-smelling vaginal discharge.

• Pelvic pain.

• Symptoms suggestive of vesicovaginal or rectovaginal fistula.

Definitive diagnosis requires histological confirmation following biopsy.

Investigations

Laboratory investigations

• Full blood count (FBC).

• Liver function tests (LFTs).

• Renal function tests (RFTs).

• HIV test.

Imaging investigations

• Chest X-ray (CXR).

• Ultrasound of the abdomen and pelvis.

• Magnetic resonance imaging (MRI) of the pelvis.

• Computed tomography (CT) scan of the abdomen and pelvis.

• Positron emission tomography/computed tomography (PET/CT).

Histological confirmation

• Bimanual examination under anesthesia (EUA).

• Cervical biopsy.

Management

Management depends on the stage of disease, the patient's general condition, fertility wishes, renal function, and the presence or absence of metastatic disease.

All patients with suspected or confirmed cervical cancer should be referred to specialized cancer centers for definitive management.

Non-pharmacological treatment

Stage IA1

• Simple hysterectomy.

• If fertility preservation is desired, cervical conization may be considered.

Stage IA2–IB2

• Wertheim hysterectomy with bilateral pelvic lymph node dissection.

• Radiotherapy may be administered postoperatively or as definitive treatment.

• No benefit has been demonstrated for adjuvant chemotherapy.

Stage IB2, IIA and IIB

• External beam radiotherapy:

  • 2.0 Gy per fraction to a total dose of 50 Gy.

• High-dose-rate (HDR) brachytherapy:

  • 8.0 Gy × 3 fractions.

• Chemotherapy may be added depending on renal function.

Stage IIIA and IIIB with good renal function and no distant metastasis

• External beam radiotherapy:

  • 2.0 Gy per fraction to a total dose of 50 Gy.

• HDR brachytherapy:

  • 8.0 Gy × 3 fractions.

Stage IIIA and IIIB with poor renal function

• External beam radiotherapy:

  • 2.5 Gy per fraction to a total dose of 50 Gy.

• No HDR brachytherapy.

• No chemotherapy.

Stage IVA with good general condition and no VVF or RVF

• Curative external beam radiotherapy:

  • Total dose of 50 Gy.

• Brachytherapy may be added.

Alternatively, palliative radiotherapy may be provided:

• 20 Gy in 5 fractions; or

• 30 Gy in 10 fractions; or

• 10 Gy as a single fraction monthly for 2 fractions.

Advanced Stage IIIB or Stage IVB with poor general condition

• Palliative care.

• Supportive care.

Pharmacological treatment

Chemotherapy may be administered as a radiosensitizer during radiotherapy or for palliative treatment in recurrent, persistent, or metastatic disease.

Concurrent chemoradiotherapy

Cisplatin

• 40 mg/m² intravenously once weekly during radiation therapy.

• Maximum dose: 70 mg weekly.

For patients with HIV infection or mild renal impairment:

Cisplatin

• 30 mg/m² intravenously once weekly during radiation therapy.

• Maximum dose: 60 mg weekly.

Palliative chemotherapy options

The following agents may be used as single agents or in combination regimens for metastatic, recurrent, or persistent disease after radiotherapy:

• Cisplatin.

• Paclitaxel.

• Bevacizumab.

• Carboplatin.

• Docetaxel.

• Gemcitabine.

Monitoring during chemotherapy

Before each chemotherapy cycle:

• Full blood count (FBC).

• Urea.

• Creatinine.

Management according to underlying cause

Not applicable, as cervical cancer is a malignant disease primarily associated with persistent HPV infection and managed according to disease stage rather than underlying etiology.

Referral

Refer all patients with suspected or confirmed cervical cancer to specialized cancer treatment centers for definitive diagnosis, staging, and management.

Urgent referral is required for:

• Histologically confirmed cervical cancer.

• Advanced disease.

• Suspected fistula formation.

• Recurrent disease.

• Metastatic disease.

Complications

• Severe vaginal bleeding.

• Chronic pelvic pain.

• Urinary tract obstruction.

• Hydronephrosis.

• Vesicovaginal fistula.

• Rectovaginal fistula.

• Local recurrence.

• Distant metastasis.

• Treatment-related complications.

• Death.

Prognosis

Prognosis depends on the stage at diagnosis and access to appropriate treatment. Early-stage disease has a favorable prognosis and may be cured with surgery or radiotherapy. Advanced disease is associated with higher morbidity and mortality, although palliative treatment can improve quality of life and symptom control.

Prevention

• HPV vaccination.

• Delayed onset of sexual activity.

• Reduction in the number of sexual partners.

• Smoking cessation.

• HIV prevention and treatment.

• Regular cervical cancer screening.

All women aged 25 years and above should undergo regular cervical cancer screening using:

• Visual inspection with acetic acid (VIA).

• Visual inspection with Lugol's iodine (VILI).

• Papanicolaou (Pap) smear.

Follow-up

• First follow-up visit: 4–6 weeks after completion of treatment.

• Thereafter every 3–6 months during the first 2 years.

• Annual follow-up after the first 2 years.