Cervical Cancer

Aetiology and Pathophysiology

The majority (70%) of cervical cancers are squamous cell carcinomas. Of the remainder, 15% are adenocarcinoma and 15% are mixed in type.

Cervical cancer usually develops as a progression from cervical intraepithelial neoplasia (CIN). This occurs over the course of 10-20 years, although not all cases of CIN progress to cancer (and most spontaneously regress).

Invasive cervical cancer occurs when the basement membrane of the epithelium has been breached. The most common sites of metastasis are the lung, liver, bone and bowel.

The vast majority of cervical squamous cell cancers are caused by persistent human papillomavirus (HPV) infection. Indeed, 99.7% of cases contain HPV DNA within the cancerous cells.

National Cancer Institute

Fig 1
Cervical cancer usually develops as a progression from cervical intraepithelial neoplasia (CIN).

Risk Factors

As discussed above, infection with human papilloma virus is the greatest risk factor for cervical cancer. Other risk factors include:

• Smoking
• Other sexually transmitted infections
• Long-term (> 8 years) combined oral contraceptive pill use
• Immunodeficiency (e.g. HIV)

Clinical Features

The most common presenting symptom of cervical cancer is abnormal vaginal bleeding (e.g post-coital, intermenstrual or post-menopausal). Other clinical features include vaginal discharge (blood-stained, foul-smelling), dyspareunia, pelvic pain and weight loss.

However, it is often asymptomatic – particularly in the early stages of disease – and many cases are detected through routine screening.

In advanced disease, the patient may experience oedema, loin pain, rectal bleeding, radiculopathy and haematuria. These often occur as a result of the cancer invading into nearby structures.

A thorough clinical examination is required in cases of suspected cervical cancer and includes:

• Speculum examination – assess for evidence of bleeding, discharge and ulceration.
• Bimanual examination – assess for pelvic masses.
• GI examination – assess for hydronephrosis, hepatomegaly, rectal bleeding, mass on PR.

By Cancer Research UK [CC BY-SA 4.0], via Wikimedia Commons

Fig 2
Cervical cancer can invade other structures in the pelvis. If the urinary system is involved, this can cause loin pain, haematuria and urinary retention.

Differential Diagnoses

There are a large number of possible causes for abnormal vaginal bleeding. These include sexually transmitted infection, cervical ectropion, polyp, fibroids, and pregnancy related bleeding.

In the post-menopausal population, always exclude endometrial carcinoma.

Investigations

In a woman presenting with symptoms suggestive of cervical cancer, the initial investigation depends on age:

• Pre-menopausal – test for chlamydia trachomatis infection
  • If positive; treat for chlamydia infection. If symptoms persist after treatment, refer for colposcopy and biopsy.
  • If negative; a colposcopy and biopsy is usually performed.

• Post-menopausal – urgent colposcopy and biopsy.

A colposcopy is where a colposcope (modified microscope) is used to produce a magnified view of the cervix. Acetic acid is used to stain dysplastic areas, and a biopsy is taken.

If the diagnosis of cervical cancer is confirmed, further investigations are required:

• Basic blood tests – such as full blood count, liver function tests and urea & electrolytes
• CT Chest-Abdomen-Pelvis – looking for metastases.
• Further staging scans – e.g. MRI pelvis, PET.
• +/- examination under anaesthesia with further biopsies.

Note: The cervical cancer screening programme aims to detect pre-invasive disease (i.e CIN). Cervical smears are not used to detect cervical cancer.

2011. The Korean Society for Therapeutic Radiology and Oncology [CC-BY-NC 3.0]

Fig 3
T2-weighted sagittal magnetic resonance (MR) image obtained prior to concurrent chemoradiation therapy shows hyper intense cervical cancer (asterisk) in the cervical canal.

Management

In the management of cervical cancer, it is important to consider the stage of disease, co-morbidities and fertility issues when deciding on treatment.

As with all cancers, treatment involves multidisciplinary input. Possible options include surgery, radiotherapy, and chemotherapy.

Surgical Options

The available surgical options are dependant on the stage of the cancer:

Stage 1a

Radical trachelectomy if fertility-preservation is a priority. This involves removal of the cervix and upper vagina. Otherwise, a laparoscopic hysterectomy with pelvic lymphadenectomy is offered.

Stage 1b/2a

Radical (Wertheim’s) hysterectomy as a curative treatment modality. Involves removal of the uterus, vagina and parametrial tissues up to the pelvic sidewall, plus lymphadenectomy.

Stage 4a or Recurrent disease

Anterior/posterior/total pelvic extenteration. Removal of all pelvic adnexae plus bladder (anterior)/rectum (posterior or both (total).

Radiotherapy

Radiotherapy is often a combination of external beam therapy and intracavity brachytherapy. If offers an acceptable alternative to surgery in early-stage disease.

Stage 1b to 3

Offered in conjunction with chemotherapy over a 5-8 week course. Evidence suggests additional hysterectomy offers no benefits in terms of survival for these stages. Therefore chemoradiation therapy is the gold standard.

By Cancer Research UK [CC BY-SA 4.0], via Wikimedia Commons

Fig 4
Radiotherapy can be delivered in the form of intracavity brachytherapy.

Chemotherapy

Chemotherapy in cervical cancer is often cisplatin-based.

It can be given before treatment by surgery or radiotherapy (known as neoadjuvant chemotherapy), or after treatment (adjuvant chemotherapy).

It is also the mainstay of treatment in the palliative setting.

Follow-Up

Patients should be reviewed by a gynaecologist every 4 months after treatment has been completed for the first 2 years, and every 6-12 months for the subsequent 3 years.

All follow-ups should involve a physical examination of the vagina and cervix (if they haven’t been removed).

Note – Cervical smear testing is no longer valid after radiotherapy.