The majority of the cancers of the cervix arise from the lining covering (epithelium) of the neck of the womb and are squamous carcinomas (85-90%of all cases). A minority of cases of cancer of the cervix have adenocarcinomas that arise from the glands of the lining of the neck of the womb, and occasionally there are features of both types visible down the microscope (adenosquamous type).
Incidence of cervical cancer
Cervical cancer is the second most common female cancer on a worldwide basis and in some developing countries, it is the commonest cancer of all (e.g. India). In the UK, the incidence is approximately 1.25%.
There is a link between incidence and sexual behaviour, there being a higher incidence in those who start sexual activity in their early teens and have many sexual partners. Both low socioeconomic status and multiparity (many pregnancies) are also related, although these factors may not be unconnected to the others. Barrier contraceptive use seems to protect.
It is hoped that the immunisation programme of teenage girls with the HPV (human papiloma virus) vaccine will further decrease the incidence of cervical cancer in the years to come.
Causes of cervical cancer
The predisposing factors seem to suggest an infective (transmissible) agent to be linked to causation and the human papilloma virus (HPV) is the agent that has been most firmly implicated; the likelihood of infection is linked with the number of sexual partners. It is certainly not the case that infection with this agent is always carcinogenic, but it is a ‘trigger’ on the steps to carcinogenesis. The newly available HPV vaccination programme (aimed at teenage girls) is specifically aimed at reducing the HPV infection promotion of cervical cancer.
Other factors that have been related to a higher incidence of the disease are smoking and immunosuppression (e.g. renal transplant recipients have a higher risk).
Once the cancerous changes occur, there is a pre-invasive stage (CIN) which precedes the more dangerous invasive cancer stage (when the cancer cells have breached the basement epithelium of the cervix and hence gained access to blood vessels/potential routes of spread). This pre-invasive stage can last for years and it is for this reason that the screening programme is so effective because detection at this stage allows pre-emptive cure of the whole condition.
Symptoms of cervical cancer
The majority of patients come to the doctor because of abnormal vaginal episodes of bleeding (after sex, in between regular periods, after the menopause etc.) or just a persistent vaginal discharge which is watery or blood tinged. Pelvic pain is a later symptom in most cases.
Treatment of cervical cancer
Under direct vision, the precancerous stage cervical intraepithelial neoplasia (CIN) may be removed by several techniques, such as laser vaporisation, radical diathermy or surgical excision – cone biopsy being a surgical excision where the whole circumferential epithelium (lining layer) is removed.
This last surgical option is currently favoured for therapy, and particularly where there is microinvasion of a millimetre or so (Stage 1a (1). Where there is deeper invasion, then a complete hysterectomy (removal of the womb) is the safer option for Stage 1a, unless the patient refuses for reasons of keeping her fertility.
For the other stages of invasive cancer, more extensive surgery or radiotherapy or both are required to effect the highest cure rates and these must be followed as appropriate, because there is a low chance of ‘second time cure’, i.e. the doctors have one chance only at a good cure chance.
Extensive surgery is the treatment of choice for younger patients with early stage disease (Stage 1-2) although radiotherapy is an acceptable alternative for those unwilling to undergo the large operation.
In the operation, which is called a Wertheim’s hysterectomy (or an extended hysterectomy) the womb and all local pelvic lymph nodes are removed as well as a cuff of vagina. Sometimes, it may be safe to leave the ovaries in. An advantage over radiotherapy is that the vagina remains moist and pliable (albeit shorter), whereas it tends to become dry and can be contracted after radiotherapy. The complications of surgery are those of any major abdominal/pelvic operation but also include the possibility of some leg swelling due to the removal of some lymph nodes which are shared by the pelvis and legs; this is rarely severe. Sometimes the control of the bladder is affected by this operation and the patient has to self-catheterise post-operation, occasionally permanently.
Radiotherapy is an alternative to surgery and has comparable cure rates which are 80% for stage 1 and 60% for stage 2 disease. Radiotherapy usually starts with external beam therapy which comprises a long course of outpatient radiotherapy. The patient attends each week day and lies on a treatment couch, whereupon a beam treats from the front, the sides and often the back to concentrate the ionising radiation dose on the central pelvis where the womb lies, and encompasses the regional pelvic lymph nodes. Each day the treatment is directed at the same place and slowly (in a fashion which is better tolerated by the normal pelvic contents than a small number of large treatments) the dose builds up on the cancer and proves ultimately fatal for the growth in the majority of cases.
Recently, it has been demonstrated that the use of a chemotherapy agent (cis-platinum) during radiotherapy (usually as an intravenous injection on all the days of the first and last week of the therapy), has improved the results of radiotherapy and this is now routinely incorporated into this initial radiotherapy course. At the end of this conventionally fractionated course of external beam radiotherapy, it is usual to boost the dose to the cervix by an intravaginal application of brachytherapy (the insertion of an applicator with components either side of the cervix in the vaginal vault and an intrauterine tube source, all three components carrying sealed source radioactive sources).
The rationale of this brachytherapy is that it allows the delivery of a very high dose of ionising radiation, which is concentrated on the cervix and rapidly tails off as one goes away from the cervix. . By the inverse square law (the law that says that if you are in a ship at sea and you treble your distance from a lighthouse, then the intensity of the lighthouse beam reduces to one ninth) the intense dose of radiation is confined to the local region around the cervix. It has been found that brachytherapy alone yields less good results than the combination with the external beam therapy because the external beam course treats disease wider of the cervix (i.e. it treats the early spread e.g. to the pelvic lymph nodes).
Conversely, brachytherapy adds to the good results of external beam therapy because it boosts the dose to the highest site of risk (i.e. the cervix itself) - See the figure posted in the outcomes section of this website. The brachytherapy sources may be sited under an anaesthetic or in the conscious patient, depending on the circumstances.
Where the patient has presented with heavy vaginal bleeding, there may be a case for using brachytherapy first, but in all other instances there is a clear rationale for shrinking the disease in towards the cervix and then boosting with brachytherapy.
The side effects of radiotherapy can be divided into the early ones like diarrhoea and bladder disturbances, together with sore pelvic skin, and late ones which include a small incidence of bowel problems, occasionally severe. Ureteric problems and occasionally rectal problems have followed high dose radiotherapy and brachytherapy plays a part in the risks. Vaginal dryness and the loss of sexuality is a problem that can be partly addressed by vaginal lubricants and HRT (hormone replacement therapy).