Clinical presentation
Many early lesions and microinvasive carcinomas are asymptomatic and are detected by cervical screening.
Those with larger lesions present with postcoital bleeding, intermenstrual bleeding or postmenopausal bleeding. Some patients will complain of a profuse, offensive vaginal discharge, which may be blood- stained. Other symptoms, such as pain, are uncommon until a very late stage.
136 Malignant disease of the uterus and cervix
Figure 12.6 A hysterectomy specimen with cervical cancer.
(Courtesy of Mr KS Metcalf.)
In all patients with abnormal vaginal bleeding, the possibility of either a cervical or uterine carcinoma should be considered and only be discounted after both have been formally excluded. Sometimes cer- vical cancer presents with bleeding during pregnancy.
Cancer of the cervix may not be clinically obvious to a general practitioner until it has become very large.
It may look like a friable polyp or an ulcerated area.
It often bleeds on contact. However, it is usually eas- ier to feel a cervical cancer than to see it because the cervix becomes stony hard. The surface may be friable.
As the carcinoma grows into the surrounding tissue, the cervix becomes less and less mobile. Figure 12.6 shows a hysterectomy specimen with cervical carcin- 0ma. A combined vaginal and rectal examination will allow a more thorough clinical assessment of the paracervical tissues. Occasionally pyometra occurs, causing uterine enlargement.
Pathophysiology
Most cervical carcinomas are of the squamous cell type, resembling the epithelium of the ectocervix.
The other principal type is adenocarcinoma with cells resembling the epithelium lining the endocervical canal. Because cervical screening is less effective in preventing adenocarcinoma of the cervix, this type has become more common in recent years and now accounts for 15-20 per cent of cases. Both of these car- cinomas arise close to the SCI, where the process of metaplasia is shifting the path of differentiation from glandular epithelium of the canal lining to squamous
epithelium of the ectocervix. Presumably both the ade- nocarcinoma and the squamous carcinoma arise from the same precursor cells and, interestingly, the bio- logical behaviour of both common types of carcino- ma is very similar (see Fig. 12.1).
Carcinoma of the cervix may spread by direct infil- tration and via the lymphatic vessels. The tumour may spread downwards into the vaginal wall, forward into the bladder, laterally into the parametrium and paracolpos, or posteriorly into the rectum. Lymphatic spread occurs outwards in the parametrium to the external and internal iliac nodes, including those in the obturator fossa, and to the common iliac and para- aortic nodes. Blood spread occurs late in the process.
Staging
The FIGO classification is based on an examination under anaesthetic with an intravenous urogram and cystoscopy (Table 12.1). Special imaging techniques and the results of subsequent surgical findings are not included. The staging is designed to be applicable whether the patient is treated in the developing world, where high technology imaging is not avail- able, or by radiotherapy, where later surgical findings cannot be included.
Treatment
Pre-clinical lesions - Stage Ia
Patients who have preclinical invasive disease that invades to a depth of less than 3 mm and a width of 7 mm can be treated safely by complete local excision.
This is usually in the form of a colposcopically directed cone biopsy type of procedure performed with a knife, laser, LLETZ or NETZ.
Patients with disease invading to a depth of between 3 and 5 mm have a risk of nodal disease of approximately 5 per cent and probably have a higher risk of local recurrence. Accordingly, unless the patient is very keen to be treated conservatively, these patients should be offered radical tre(l~ment.
Clinical invasive cervical carcinoma - Stage Ib-IV Treatment for clinical invasive carcinoma is by surgery, radiotherapy or a combination of the two.
Chemotherapy has gained an important place in con- junction with radiotherapy such that chemoradiation has replaced radiotherapy in all women sufficiently fit to undergo this more toxic treatment.
If the disease is apparently confined to the cervix, either surgery or chemoradiotherapy may be offered.
Table 12.1 The 1998 FIGO staging classification for cervical cancer
Stage Description
o
Pre-invasive carcinoma (carcinoma in situ, CIN)Carcinoma confined to the cervix (corpus extension should be disregarded)
Ia Invasive cancer identified only microscopically All gross lesions, even with superficial
invasion, are Stage Ib cancers
Depth of measured stromal invasion should not be greater than 5 mm and no wider than 7mma
Ia1 Measured invasion no greater than 3 mm in depth and no wider than 7 mm
Ia2 Measured depth of invasion greater than 3 mm and no greater than 5 mm and no wider than 7 mm
Ib Clinical lesions confined to the cervix or pre-clinical lesions greater than Ia Ib 1 Clinical lesions no greater than 4 cm in size Ib2 Clinical lesions greater than 4 cm in size II Carcinoma extending beyond the cervix and
involving the vagina (bu t not the lower third) and/or infiltrating the parametrium (but not reaching the pelvic side wall) IIa Carcinoma has involved the vagina IIb Carcinoma has infiltrated the parametrium III Carcinoma involving the lower third of the
vagina and/or extending to the pelvic side wall (there is no free space between the tumour and the pelvic side wall)
IlIa Carcinoma involving the lower third of the vagina
IIIb Carcinoma extending to the pelvic wall and/
or hydronephrosis or non-functioning kidney due to ureteric obstruction caused by tumour IVa Carcinoma involving the mucosa of the
bladder or rectum and/or extending beyond the true pelvis
IVb Spread to distant organs
aThe depth of invasion should not be more than 5 mm from the base of the epithelium, either surface or glandular, from which it originates. Vascular space involvement, either venous or lymphatic, should not alter the staging.
Malignant disease of the cervix 137
Both forms of treatment are probably equally eft ct- ive, although for premenopausal women in particu- lar, surgery is thought to offer lower morbidity. Once the disease has spread outside the cervix, chen ora- diotherapy is usually the mainstay of treatment.
Surgery
The standard surgical procedure for carcinoma of the cervix is a Wertheim hysterectomy, which involves removal of the uterus and the paracervical tissues sur- rounding the cervL,\: and the upper vagina. In addition, the pelvic lymph nodes are carefully dissected as a therapeutic manoeuvre to remove as many of the nodes as possible. The pelvic lymph nodes include the exter- nal iliac, internal iliac, common iliac, obturator and presacral nodes.
The dissection of the pelvic nodes is both diagnos- tic and therapeutic. If a large number of nodes are involved, it is usual to offer the patient adjuvant radio- therapy. However, if only one or two lymph nodes are involved, the pelvic dissection may well be thera- peutic. The ovaries may be conserved, particularly if the patient has a squamous tumour.
Although the vagina is shortened by 2-3 cm, the remaining vagina is pliable and physical sexual function is preserved. The principal complications seen follow- ing this procedure are related to difficulty with com- plete bladder emptying because of division of the parasympathetic nerve supply to the bladder that runs within the uterosacral ligament.
Careful attention to bladder emptying to prevent urinary retention is important in the immediate post- operative period. On rare occasions, patients suffer from lymphoedema of the legs and mons pubis. This is more common after postoperative radiotherapy.
Radiotherapy
Radical radiotherapy for cervical carcinoma involves the use of a linear accelerator to treat the ,«~ole pelvis with external beam therapy to shrink the central car- cinoma and also to treat the possible sites of regional metastasis. Internal sources are then placed in the upper vagina and within the canal of the cervix to provide a very high dose to the central tumour. The external beam therapy is usually given in approxi- mately 25 fractions over a 5-week period, follovved by two internal treatments in the following week. Most patients tolerate this treatment well, although some damage to the bladder and bowel is inevitable.
138 Malignant disease of the uterus and cervix
Diarrhoea during treatment is usual, although this often settles after treatment is finished. A radiation menopause is induced in premenopausal women and inevitably there is some loss of elasticity within the vagina with narrowing. This can be reduced by the use of vaginal dilators and early resumption of intercourse.
Radiotherapy is also used in an adjuvant setting following surgery if more than one or two lymph nodes are positive, if excision margins are close or if the tumour was bulky and had a high chance of recurrence. In advanced cancer of the cervix, radio- therapy may be used in a palliative setting to reduce vaginal bleeding and discharge and to assist in local control of the disease. Chemotherapy may also be used in an adjuvant setting. Response rates are typic- ally 60 per cent, and chemotherapy may be used in the neoadjuvant setting prior to surgery rather than following surgery.
Carcinoma of the cervix and pregnancy
Difficult problems may arise if a woman with cervical carcinoma is also pregnant. In early pregnancy, exter- nal irradiation may be given; abortion of a dead fetus will follow and then local irradiation with caesium can be given. Later in pregnancy, the uterus must be emptied by hysterotomy or Caesarean section before radiotherapy can be given. Many surgeons prefer to treat these cases by Wertheim hysterectomy at the time of Caesarean section.
Pelvic exenteration
Pelvic exenteration may be considered in a few selected cases of recurrent disease after radiotherapy, where the disease has spread into the bladder or rectum but where there is no evidence of distant metastases. The morbidity of this surgery can be considerable.
Anterior exenteration consists of removal of the uterus, vagina and bladder, with implantation of the ureters into an artificial bladder made from an ileal loop. If the rectum also has to be removed in a total exenteration, a terminal colostomy is formed.
Carcinoma of the cervical stump after hysterectomy
The stump of cervix left after subtotal hysterectomy is just as prone to the development of carcinoma as when