Cervical Carcinoma

Synonyms: cervical cancer, cancer of the (uterine) cervix, carcinoma of the (uterine) cervix

Incidence

The age-standardised (European) annual incidence rate of cervical cancer is 13.2 per 100,000 females.Age-standardised mortality rate for the UK was 2.9 per 100,000 in 2008.

Risk factors

• Heterosexual women.
• Infection with human papilloma virus (HPV), predominantly types 16 and 18 (infection present in around 95% of cases).
• Women with multiple sexual partners, or partners of promiscuous males.
• Smoking.
• Lower social class.
• Immunosuppression ,eg HIV, and post-transplant.
• There is a slight increase in risk with use of a combined oral contraceptive.
• Non-attendance at the cervical screening programme.

Pathogenesis

Three types of primary tumour are generally seen:

• Bulky, ectocervical tumour, which fills the upper vagina.
• Invasive, bulky tumour that can enlarge to a size where it fills the lower pelvis.
• Destructive, invasive tumour that erodes tissue, causing ulceration and excavation with infected, necrotic cavities.

Histopathology

70% are squamous carcinomas, 15% mixed pattern, and 15% adenocarcinoma, all three of which cause both pre-invasive and invasive disease.

Cervical intraepithelial neoplasia (CIN) - disease confined to the epithelium

CIN I : disease confined to the lower third of the epithelium. CIN II: disease confined to the lower and middle thirds of the epithelium. CIN III: affecting the full thickness of the epidermis.

Invasive carcinoma

This breaches the epithelial basement membrane at any point.

• If the deepest invasive element is <5 mm from the surface of the epithelium then it is defined as micro-invasive carcinoma.
• If it extends beyond 5 mm or is wider than 7 mm then it is defined as invasive carcinoma and formal staging is required.

Presentation

Many cases are detected by screening. However, symptoms require full pelvic examination including use of a speculum.

The first symptoms of established cervical carcinoma are:

• Vaginal discharge; this varies greatly in amount and can be intermittent or continuous.
• Bleeding; this can be spontaneous but may occur after sex, micturition or defecation, in the early stages. Patients may ignore this if it is scanty and ascribe it to normal menstrual dysfunction. Occasionally, severe vaginal bleeding may necessitate emergency hospital admission.
• Vaginal discomfort/urinary symptoms.

Late symptoms

• Painless haematuria.
• Chronic urinary frequency.
• Painless fresh rectal bleeding.
• Altered bowel habit.
• Leg oedema, pain and hydronephrosis leading to renal failure are ominous, late signs indicating pelvic wall involvement.
• With more advanced disease, patients develop pelvic discomfort or pain that is poorly localised and described as dull or boring in the suprapubic or sacral regions. It is similar to menstrual discomfort, can be persistent or intermittent and may be confused with arthropathy.

NB: symptoms may prompt the patient to seek a cervical smear. A smear test is useful for detecting precancerous lesions, but not carcinoma. If there is any degree of suspicion of cervical carcinoma then examine carefully and consider urgent referral for further assessment.

Signs

In early-stage cervical cancer, examination can be relatively normal.

• There may be white or red patches on the cervix. As the disease progresses, it can lead to an abnormal appearance of the cervix and vagina, due to erosion, ulcer or tumour.
• Rectal examination may reveal a mass or bleeding due to erosion.
• Bimanual palpation may reveal pelvic bulkiness/masses due to pelvic spread.
• Leg oedema may develop due to lymphatic or vascular obstruction.
• Hepatomegaly may develop in the case of liver metastases.
• Pulmonary metastases are normally only detected if they cause pleural effusion or bronchial obstruction.

Differential diagnosis

• Cervicitis.
• Dysfunctional uterine bleeding.
• Cervical erosion (ectropion).
• Pelvic inflammatory disease.
• Endometrial carcinoma.
• Side-effects of intrauterine contraceptive device (IUCD) use.
• Endometrial hyperplasia.
• Fibroids.
• Atrophic vaginitis.

Investigations

• Premenopausal women presenting with abnormal vaginal bleeding should be tested for Chlamydia trachomatis.
• Postmenopausal women should be referred urgently to gynaecology for assessment.
• Colposcopy - allows examination of the visible cervix, usually including the transformation zone:
  • The cervix is first cleaned with acetic acid.
  • The cervix can then be inspected, biopsied and treated if necessary.
• Cone biopsy.
• FBC (for anaemia) - haemoglobin level should be monitored during chemoradiotherapy and corrected if it falls below 12 g/dL.
• Renal function tests, LFTs.
• CXr (to seek metastases) and IV urogram.
• CT scanning of the pelvis and abdomen - used to stage disease, along with relevant biopsies.
• Barium enema or proctoscopy - used to assess rectal compression/invasion.
• Cystoscopy - to assess bladder invasion.
• MRI - gives a clear picture of a primary tumour, local invasion and nodal enlargement.

Staging

The staging system of the International Federation of Gynecology and Obstetrics (FIGO) is most commonly used.^[1]

• 0: carcinoma in situ (pre-invasive).
• I: cervical carcinoma confined to the cervix (disregard extension to corpus).
  • Ia: invasive carcinoma diagnosed only by microscopy (all visible lesions, even superficial ones are 1B).
    • Ia1: stromal invasion to maximum 3 mm depth and 7 mm horizontal spread.
    • Ia2: stromal invasion >3 to <5 mm with 7 mm horizontal spread.
  • Ib: clinical visible lesions confined to the cervix or lesion visible on microscopy >IA2.
    • Ib1: clinically visible lesion 4 cm in largest dimension.
    • Ib2: clinically visible lesion >4 cm in largest dimension.
• II: tumour invades beyond the uterus but not to the pelvic wall or the lower third of the vagina.
  • IIa: no parametrial invasion.
  • IIA1: clinically visible lesion ≤4.0 cm in greatest dimension.
  • IIA2:clinically visible lesion ≥4.0 cm in greatest dimension.
  • IIb: parametrial invasion (but not the pelvic sidewall).
• III: tumour extends to the pelvic wall and/or involves the lower third of the vagina and/or causes hydronephrosis or the kidney not to function.
  • IIIa: tumour involves the lower third of the vagina - no extension to the pelvic wall.
  • IIIb: tumour extends to the pelvic wall and/or causes hydronephrosis or the kidney not to work.
• IV: further spread.
• IVa: tumour invades the mucosa of the bladder or rectum and/or extends beyond the true pelvis.
• IVb: distant metastases.

Prognosis

Approximate 5-year survival depends upon the stage.

Stage	5-year survival rate (%)
Ia1 Ia2	98-99% 95-98%
Ib1 Ib2	90-95% 80%
IIa IIb	70-90% 60-70%
IIIa/b	30-50%
IVa	>20%
IVb	<20%

Prevention

• Cervical smear
• Human Papillomavirus (HPV) Vaccination.