carcinoma of cervix

Carcinoma of the cervix:
Carcinoma of the cervix is the second commonest cancer among women worldwide, with only breast cancer occurring more commonly.
Worldwide, cervical cancer accounts for about 500,000 new cases diagnosed and 250,000 deaths every year. Of the new cases, 80% occur in the less developed countries and in some of these countries, cervical cancer is the commonest cancer in women.
HPV types 16 and 18 are the most commonly associated with cervical cancer, but many other types are also found. The range of types and proportions of each type vary markedly in different parts of the world. The association between HPV infection and cervical cancer has led to the development of vaccines both to prevent and to treat this disorder and its precursors (CIN).
While it is now technically possible to construct a large range of different vaccines, many years of fieldwork will be necessary to evaluate their efficacy, acceptability and effect upon the prevalence of other HPV subtypes.
*(risk factors for cervical carcinoma):
1- HPV infection.
2- early marriage.
3- multiple sexual partners.
4- liberal sex.
5- young age at 1st pregnancy.
6- high parity.
7- lower socioeconomic status.
8- smoking.

Cervical cancer presentation

1)- Women may present asymptomatically (when early or microinvasive) the disease is detected as a result of abnormal cervical cytology.
2)- In more advanced lesions, there are usually symptoms raising the possibility of cervical cancer. These include:
1- post-coital bleeding,
2- intermenstrual or postmenopausal bleeding.
3- offensive blood- stained vaginal discharge( may be profuse).
4- If there is abnormal bleeding during pregnancy, then a cervical lesion needs to be excluded.
3)- In some women presenting with late disease: there may be
1- backache,
2- leg pain,
3- leg oedema,
4- haematuria,
5- bowel changes,
6- malaise,
7- weight loss.

Diagnosis

1- A full history and
2- clinical examination is undertaken.
if the tumour is large it may look like a friable polyp or an ulcerated area that
bled on contact, or atypical consistency on bimanual examination.
If the referral is due to cervical cytology suspicious of invasion, then
3- acolposcopic examination should be performed.

Suspicious features at colposcopy include:
1- intense acetowhiteness,
2- atypical vessels,
3- raised/ulcerated surface.
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4- Definite diagnosis is based on histolopathological study of appropriately
taken biopsies.

Histology
The majority of cervical cancers are squamous (80–85%) and the remainder is adenocarcinoma, and adenocarcinoma elements has been rising.
Presumably both the adenocarcinoma and the squamous carcinoma arise from the same precursor cells and the biological behaviour of both common types of carcinoma is very similar.
Rarer histological types include clear cell, lymphomas and sarcomas.


Spread:
Carcinoma of the cervix may spread by direct infiltration 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 disease.

Staging:
After diagnosis of cancer it must be staged, why?
1) the treatment can be planned appropriately.
2) the staging will also give an idea of prognosis.

Staging should include an assessment of disease, extent and sites of spread.
It is clinical staging although early cancers are staged according to the surgical specimen.
Clinical assessment and investigations for initial evaluation of the stage:
• Examination under anaesthesia which should include a combined recto-vaginal assessment.
• Biopsy of the suspicious area. It should be either wedge or cone shaped to obtain sufficient material for histological assessment.
• Cystoscopy.
• Sigmoidoscopy.
• CXR and IVU.
• Other imaging as indicated such as: computerized axial tomography (CT) scan and Magnetic Resonance Imaging (MRI) Scan



Stage 0 Carcinoma in situ, cervical intraepithelial neoplasia grade III
Stage I The carcinoma is confined to the cervix.
IA Invasive carcinoma (microscopical) stromal invasion is less than 5 mm and extension is less than 7 mm.
IB Clinically visible lesions (macroscopical) or preclinical cancers greater than stage IA

Stage II Cervical carcinoma invades beyond the uterus, but not to the pelvic wall or to the lower third of the vagina
IIA No obvious parametrial involvement
IIB Obvious parametrial involvement

Stage III The carcinoma has extended to the pelvic wall. On rectal examination, there is no cancer-free space between the tumour and the pelvic
wall. The tumour involves the lower third of the vagina. All cases with hydronephrosis.
IIIA Tumour involves the lower third of the vagina, with no extension to the pelvic wall
IIIB Extension to the pelvic wall and/or hydronephrosis or non-functioning kidney

Stage IV The carcinoma has extended beyond the true pelvis or has involved (biopsy-proven) the mucosa of the bladder or rectum.
IVA Spread of the growth to adjacent organs
IVB Spread to distant organs

Treatment:
For stage 0 local excision or ablation as mentioned.
stage 1 preclinical (microscopical) the treatment is conservative by local excision (a colposcopically directed cone biopsy), and some times if the lesion is deeply invading (between 3-5 mm) there is risk of node spread 5% if treated conservatively so it need more radical surgery.
From stage 1 B to stage IV the treatment is ranging between radical surgery to combined surgery and radiotherapy or combined radiochemotherapy accordingly
If the disease is apparently confined to the cervix either surgery or chemoradiotherapy may be offered. Both forms of treatment are probably equally effective although for premenopausal women in particular, surgery offer lower morbidity.
Surgery
The standard surgical procedure for carcinoma of the cervix is a
Wertheim hysterectomy, which involves removal of ( the uterus, the paracervical tissues surrounding the cervix, the upper vagina, the pelvic lymph nodes ) the dissection of the pelvic nodes is both diagnostic and therapeutic. If a large number of nodes are involved, the patient should recieve adjuvant radiotherapy but if only one or two lymph nodes are involved, the pelvic dissection is considered sufficient, and if the patient has a squamous tumour the ovaries may be conserved.
Although the vagina is shortened by 2-3 cm, the sexual function is preserved.
The principal complications seen following this procedure are:
1- difficulty with complete bladder emptying because of division of the parasympathetic nerve supply to the bladder that runs within the uterosacral ligament.
2- On rare occasions, patients suffer from lymphoedema of the legs and mons pubis.
Radiotherapy
Radical radiotherapy for cervical carcinoma involves the use of:
1- external beam therapy to shrink the central carcinoma and also to treat the possible sites of regional metastasis.
2- 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.

Most patients tolerate this treatment well.
Complications:
1- some damage to the bladder and bowel is inevitable, diarrhoea during treatment is usual, and is resolved after treatment is finished.
2- A radiation menopause is induced in premenopausal women.
3- some loss of elasticity within the vagina with narrowing. This can be reduced by the use of vaginal dilators and early resumption of sexual activity.

Radiotherapy is also used in an adjuvant setting following surgery:
1- if more than one or two lymph nodes are positive,
2- if excision margins are close
3- if the tumour was bulky and had a high chance of recurrence.

In advanced cancer of the cervix, radiotherapy is palliative treatment:
1- to reduce vaginal bleeding and discharge
2- to assist in local control of the disease.

Chemotherapy may also be used in an adjuvant setting, response rates are approximately 60 percent, and chemotherapy may be used in the neoadjuvant setting prior to surgery rather than following surgery.

Carcinoma of the cervix and pregnancy
1- In early pregnancy, external irradiation may be given; abortion of a dead fetus will follow and then local irradiation with caesium can be given.
2- Later in pregnancy, the uterus must be emptied by hysterotomy or Caesarean section followed by radiotherapy.
Sometimes Wertheim hysterectomy at the time of Caesarean section is done


Surgery for advanced disease or recurrent disease:
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 no evidence of distant metastases.

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.
total exenteration, same as in anterior exenteration plus removal of rectum, a terminal colostomy is also formed.
Posterior exenteration: removal of uterus, vagina, and rectum.

Carcinoma of the cervical stump after hysterectomy:
This is a clinical dilemma

Palliative treatment
Palliative treatment is required for the distressing symptoms that may arise in the advanced stages of the disease. Patients with growths that are too advanced for curative treatment and those with recurrent disease must be kept free from pain and as comfortable as possible. Expert nursing is necessary, especially when incontinence is present.

Survival
Survival is stage dependent and the advanced stages are associated with a poor prognosis. The national (UK) 5-year relative survival rate for all women treated for invasive cervical cancer is 61%.
The 5-year relative survival rates is:
80% for stage I,
74% for stage II,
47% for stage III
and 25% for stage IV.