Gab Kovacs1 and Paula Briggs2
(1)
Department of Obstetrics and Gynaecology, Monash University, Clayton, Victoria, Australia
(2)
Sexual and Reproductive Health, Southport and Ormskirk Hospital, Southport, UK
Cancer of Cervix
Definition
Incidence
Aetilogy and Pathogenesis
Clinical Assessment
Treatment
Complications
Prognosis
Endometrial Cancer
Incidence
Aetilogy and Pathogenesis
Clinical Assessment
Treatment
Complications
Prognosis
Ovarian Cancer
Definition
Incidence
Aetilogy and Pathogenesis
Clinical Assessment
Treatment
Complications
Prognosis
Cancer of Cervix
Definition
Approximately 90 % of cervical cancers are squamous in origin (arising from the stratified squamous epithelium of the cervix). The remaining 10 % are adenocarcinomas (arising from the endocervical columnar cells).
Incidence
In the UK, cervical cancer accounts for approximately 2 % of all cancers in women. Cervical cancer is the 12th commonest cancer in females with an incidence of 8/100,000.
· Due to screening programs, the incidence of cervical cancer has decreased by roughly 50 % during the last four decades.
· Cervical cancer is most common in women aged 30–34.
Aetilogy and Pathogenesis
Squamous cell carcinoma is caused by oncogenic subtypes of Human Papilloma Virus (HR-HPV), the commonest of which are type 16 and 18. Ninety eight percent of infections will resolve spontaneously due to the immune system. When the immune system is unable to prevent viral replication, precancerous changes develop, which may lead to cervical cancer. This is more likely to occur in the presence of co-factors such as cigarette smoking.
It has also been recognised for many years that cervical dysplasia develops over a number of years, long before a woman develops cancer. Recognisable graded abnormalities may be detected on cervical cytology during this time and these abnormalities are known as dyskaryosis (graded as mild, moderate and severe). Cervical cytology, first described by Papanicolaou in 1943 is used to detect these precancerous changes, and has reduced mortality.
Adenocarcinoma arises in the glands of the cervical canal. It is becoming more common in association with HPV type 18.
Clinical Assessment
History
The most significant symptom is abnormal bleeding. This can be post-coital or inter-menstrual bleeding.
Examination
A speculum examination may detect a cervical lesion (squamous cell) or abnormal tissue arising from the endo cervix (adenocarcinoma).
Investigations
Women with dyskaryosis on cervical cytology, in association with HR-HPV infection need to be investigated by colposcopy.
This is a non invasive inspection of the cervix with a binocular magnifying microscope (colposcope), often with the use of acetic acid or iodine staining, to determine the site, nature and the extent of any lesions.
A cervical biopsy should be performed for histological confirmation of any abnormality. On histological examination the changes are graded as Cervical Intraepithelial Neoplasia (CIN) I, II and III.
Low grade CIN often regresses without treatment. However in some women the changes may progress to moderate or high grade CIN, necessitating excision biopsy (large loop excision of the transformation zone (LLETZ)).
If invasive changes are diagnosed on biopsy, the cancer is staged. The woman is examined under anaesthesia, including cystoscopy and proctoscopy. A full evaluation involves a chest X-ray, a CT scan, MRI, and sometimes PET scanning.
Staging is carried out using the T (tumour extent), N (lymphatic spread) and M (metastasis) scale.
Treatment
Medical
· Hormonal – There is no hormonal treatment for CIN or cervical cancer.
· Other medical – Whilst neither CIN or cancer can be treated with anti-viral therapy at present, the incidence of HPV has significantly decreased since the introduction of HPV vaccination programs.
Surgical
· Minor – In cases of CIN the abnormal cells are removed to prevent progression of disease. The tissue is then sent to pathology for examination.
· Major – If frank invasive cervical cancer is detected, then major surgery comprising of hysterectomy, with pelvic node dissection is usually undertaken. In premenopausal women the ovaries may be conserved.
Complications
May occur due to local invasion of tissues – bladder, obstruction of the ureters and/or infiltration of the rectum, or distal metastases e.g. lung, liver, or distant lymph nodes.
Prognosis
The 5 year survival rate depends on the stage of the disease when it is diagnosed. It ranges from 93 % with low grade cancers, to 35 % for advanced cervical cancer.
Endometrial Cancer
This is usually adenocarcinoma.
Incidence
In the UK, endometrial cancer accounts for about 5 % of all cancers in women, and it is the 4th commonest cancer in females. Its incidence is about 20/100,000 women.
Endometrial cancer is most common in postmenopausal women, with 75 % being diagnosed over the age of 40.
It is more common in women who have not had children, who are obese, who have polycystic ovarian syndrome, hypertension and diabetes.
In contrast to cervical cancer, the incidence of endometrial cancer is increasing in line with the obesity epidemic.
Aetilogy and Pathogenesis
Endometrial cancer is thought to be caused by unopposed/excessive oestrogen exposure. The combined administration of oestrogen along with a progestogen as with combined oral contraception (COC) has a protective effect on the endometrium.
Clinical Assessment
History
The commonest presenting symptom is heavy menstrual bleeding (HMB) for women who are pre-menopausal, or post menopausal bleeding (PMB) in women who are menopausal.
A family history of bowel, breast or ovarian cancer is relevant.
As mentioned under incidence, nuliparity, obesity, hypertension and diabetes are all associated problems.
Examination
A speculum examination is usually normal, as is a bimanual examination.
Investigations
An ultrasound (transvaginal) may shows an abnormally thickened endometrium, with an increase in colour flow.
Endometrial sampling should be undertaken in order to obtain tissue for histological examination.
Staging is undertaken in a similar way to cervical cancer.
A hysteroscopy and possibly further biopsies should be undertaken to inspect the uterine cavity, and obtain tissue for diagnosis and staging.
Treatment
This will depend on the stage of the cancer, the size of the uterus, and the woman’s age and medical condition.
Medical
· Hormonal – As progestogens have an inhibitory effect on endometrial cancer, they may be used in recurrent disease where the tissue is positive for progesterone receptors.
· Other medical – radiotherapy (external deep x-ray therapy – DXRT, or internal radon) is sometimes used.
Chemotherapy is also sometimes used as an adjunct to surgery.
Surgical
· Minor – D & C or hysteroscopy and biopsy is part of the staging process.
· Major – This is the usual primary treatment, with total hysterectomy, and salpingo-oophorectomy being undertaken, sometimes with lymph node dissection.
Complications
Endometrial cancer can spread locally to bladder or bowel, and can obstruct the ureters. Distal metastases can also occur to lymph nodes, lung, liver, bones, brain and vagina.
Prognosis
Again, this depends on the stage of the cancer. Five year survival rates can be as high as 90 % for early cancers, to as low as 15 % for more advanced stage cancer.
Ovarian Cancer
Definition
Most of the ovarian cancers (90 %) arise from the epithelial layer on the outside of the ovary, and are epithelial cancers. The other types of ovarian cancer arise from the germ cells or from the sex-cord stromal cells.
Incidence
In the UK, ovarian cancer accounts for about 4 % of all cancers in women, and is the 5th commonest cancer in females. Its incidence is about 22/100,000 women.
Ovarian cancer is most common in postmenopausal women, with 75 % of women being diagnosed over the age of 55.
Aetilogy and Pathogenesis
There appears to be a link between ovulation and epithelial ovarian cancer. Using combined hormonal contraception reduces the risk of ovarian cancer by approximately 50 %. Having a first degree relative with ovarian cancer is a risk factor. Being a carrier of BRCA 1 and 2 genes is also a risk factor. Being overweight, tall, a smoker and using talcum powder have all been postulated to increase the risk of ovarian cancer. Taking COC, having children, breast feeding and having the tubes ligated have all been suggested to be protective against ovarian cancer.
Clinical Assessment
History
Unfortunately ovarian cancer does not have any early symptoms. When the disease spreads it may cause pain, a feeling of bloating or fullness, abdominal distention, urinary frequency, or constipation. Sometimes ovarian cancer presents with symptoms of metastasis, including nausea, tiredness, or shortness of breath.
Ovarian cancer is often diagnosed as an incidental finding on ultrasound, laparoscopy or laparotomy.
Examination
There is usually nothing to be found on examination until the disease has spread.
Investigations
· CA 125 levels in blood- This hormone is often raised in women with ovarian cancer (50 % in the early stages and up to 90 % in advanced stages). It is not diagnostic and can also be raised in women with endometriosis, fibroids, PID, and pregnancy.
· Ultrasound-although both abdominal and vaginal scanning should be performed, the vaginal view gives better resolution to asses ovarian pathology. Abnormalities detected with complex changes are more indicative of cancer. Abdominal scanning is helpful for identifying ascites.
· CT Scan- This may be undertaken if cancer is suspected. A CT scan may give a clearer view of the ovaries.
· Chest X-ray- This is undertaken to look for any lung metastases.
· Laparoscopy- sometimes a laparoscopy is undertaken to inspect the ovaries, and this may be combined with therapeutic surgery- ovarian cystectomy or oophorectomy.
Treatment
Medical
· Hormonal – tamoxifen may be used where other treatment is deemed inappropriate.
· Other medical – Chemotherapy is often used in combination with surgery (see below). Occasionally chemotherapy alone is used.
o Radiotherapy is not usually used for treating ovarian cancer. It may be used in early stage cancer post-operatively, or in advanced cancer as “palliative radiotherapy”.
Surgical
· Minor- nil
· Major –The principal behind surgery for ovarian cancer is to remove as much tumour as possible. Total hysterectomy, with bilateral salpingo-oophorectomy and omentectomy is the basic operation. Lymph nodes are sometimes removed, and if there is any other tumour in the abdominal cavity, then debulking should be undertaken. If total removal can be undertaken that gives a better prognosis.
Complications
As ovarian cancer is often not diagnosed until it is advanced, it may only come to light when it causes a complication. This could include ascites, bowel obstruction, bladder infiltration causing haematuria, or as a result of secondary deposits in liver or lung.
Prognosis
The prognosis depends on the cancer type and the stage of the disease at the time of diagnosis. For epithelial tumours, 5 year survival is as high as 90 % for early disease, but as low as 17 % for advanced disease. For ovarian stromal tumours, the range is 95–35 %, and germ cell tumours, 98–69 %.