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Cancer of the cervix (the lower end of the uterus that opens into the vagina) is one of the commonest cancers in women. Its occurrence has declined remarkably in the developing world due to an organized screening programme, early detection and improved treatment of pre-cancerous stages of the disease. The contrary is however the case in the developing world where this condition is not only the commonest genital tract cancer in women but also the leading cause of gynaecological deaths. Cervical cancer now evokes tremendous attention in the developing world where it presents significant management problems for the gynaecologist because majority of the women affected present with the advanced and incurable stages of the disease.

Anatomy of the uterus and upper vagina

Cervical cancer is a sexually-transmitted disease. Unlike most cancers, the cause is not unknown. Infection with the the oncogenic (cancer-provoking) strains of the human papillomavirus (HPV) has been established to be causative in the vast majority of cases. Up to 97% of women with cervical cancers are infected with HPV. HPV is the commonest sexually-transmitted infection. The risk factors include multiple sexual partners, early onset of sexual activity, a high-risk sexual partner (i.e. a partner with multiple sexual partners), a history of STDs and prior sexual exposure to someone with cervical cancer. Cervical cancer is not found among nuns and celibate women. Others risk factors include cigarette smoking, human immunodeficiency virus (HIV) infection, acquired immune deficiency syndrome (AIDS), other forms of immunosuppression, low socio-economic status, multiparity and long-term oral contraceptive pill use.

Pre-malignant diseases of the cervix and early stages of cervical cancer are usually not symptomatic. A woman with cervical cancer may experience watery vaginal discharge which is usually offensive and may be blood-stained. She may also experience irregular vaginal bleeding especially after (or during) sexual intercourse. Any woman with irregular vaginal bleeding should be evaluated by a gynaecologist. Also, any woman experiencing vaginal bleeding after the menopause should be evaluated. Other symptoms include poor appetite, low back, abdominal or waist pain. Weakness, weight loss, anaemia as well as the involuntary loss of urine or faeces through the vagina are manifestations of advanced disease.

Cervical cancer as seen on a saggital MRI of the pelvis

The treatment of cervical cancer varies with the stage of the disease. Radiotherapy (the use of radiation) is applicable for the treatment of all the stages. For early invasive cancer, surgery is the treatment of choice and the aim is cure. In more advanced cases, chemoradiation, that is, radiotherapy combined with chemotherapy (the use of anti-cancer medications) is the current standard of care and the aim is palliation. In patients with disseminated disease, chemotherapy or radiotherapy provides symptom palliation.

Cervical cancer is a highly preventable condition. Different levels of prevention have been described. Primary prevention involves education and lifestyle modification to prevent or reduce exposure to the risk factors earlier enumerated. Of prime importance is education of adolescents and young women on the need to delay initiation of sexual activity. Condoms are not as protective against the human papillomavirus as they are against other sexually transmitted diseases. This is because transmission can occur from mere labioscrotal or skin-to-skin contact. Where abstinence is impracticable, mutual fidelity should be strongly encouraged.

Primary prevention also involves the use of vaccines against the oncogenic strains of the HPV. This is aimed at preventing primary infection with the virus. The vaccine is to be administered before the initiation of sexual activity. Two types of vaccines are currently available. The Cervarix made by GlaxoSmithKline is an inactivated bivalent vaccine against HPV subtypes 16 and 18. Gardasil is a tetravalent vaccine made by Merck and is protective against HPV subtypes 6, 11, 16 and 18. It is equally protective against genital warts and anal cancer. Both vaccines are given as intramuscular injections of three doses at 0, 1, 6 weeks and 0, 2, 6 weeks for Cervarix and Gardasil respectively. They are licensed, safe and effective for females ages 9 through 26 years. Only Gardasil has been tested and licensed for use in males.

Secondary prevention is essentially the detection and early treatment of the pre-cancerous stages of the disease. This entails the use of cervical screening which has emerged as an extremely effective method for the prevention of cervical carcinoma. This is because unlike organs such as the ovaries, the uterine cervix is anatomically accessible and there is continuous exfoliation of cervical epithelial cells. Also, cervical carcinoma has a treatable pre-invasive stage which can be detected by studying the cellular characteristics of the exfoliated cells.

Cytological abnormalities are detected using the Pap smear, named after its inventor, George Papaniculaou. It is an office procedure in which the cervix is exposed with a speculum and cells are removed from the cervical epithelium with a cotton swab or a spatula, smeared on a slide and examined under a microscope for precancerous cellular changes and signs of malignancy.

Normal appearance of cervical epithelium

Premalignant changes on cervical epithelium

If the Pap smear reveals epithelial abnormalities, most gynaecologist will recommend that the woman undergo a colposcopy. In this procedure, which can also be performed in the office, a microscope-like instrument called a colposcope is used to provide a magnified view of the vaginal and cervical surfaces. If any abnormal or suspect tissues are noted, biopsy samples are removed using small forceps. If these samples reveal cancerous or precancerous lesions when examined under a microscope, a more extensive biopsy called a cone biopsy may be performed under general anesthesia in theatre for a definitive diagnosis. If pre-cancerous lesions are found, these are treated so that they do not progress to invasive cancer.

Histopathology image of carcinoma in-situ

HPV testing as also emerged as an adjunct to Pap smear in screening for pre-malignant lesions of the cervix. It is especially invaluable in the setting of boarderline smears or those with lesions of undetermined significance to decide on the need to refer for culposcopy. It is also used to follow up patients treated for pre-cancerous lesions.

It is recommended that women begin cervical screening with Pap smears by 21 years of age or at onset of sexual activity regardless of age. This should be done annually. After two successive negative annual smears, the interval may be lengthened to three years. For high-risk women however, screening should be carried out annually. Following removal of the uterus, vaginal smears are recommended at a minimum interval of 3–5 years. Following treatment for pre-cancerous cervical diseases, 4-6 monthly screening should be done for two years and annually thereafter if findings are normal. Following treatment for invasive cervical cancer, 3 monthly screening should be done for two years and then 6-monthly thereafter if findings are normal.

Tertiary prevention of cervical cancer involves early evaluation of symptoms and treatment of patients with suspected cervical cancer as well as complications of the disease. This is aimed at limiting the extent of the disease as well as improving the quality of life of the patient.

Currently, cervical screening using the Pap smear is the cornerstone of prevention of cervical cancer. It is targeted towards the entire population of sexually active women. This programme has been highly successful in the developed world. This is however not the case in the developing world where knowledge of cervical cancer is poor and uptake of cervical screening is low. In most centres, screening programmes are largely utilized by adult women. This is as a result of cultural barriers preventing unmarried adolescents from accessing the various entry points to reproductive health services. The result is a large population of sexually active adolescents with poor knowledge and utilization of cervical screening.