The cervix is the bottom part of, and opening to, the uterus and is contiguous with the body of the uterus.  It is a roughly cylindrical, fibro-muscular organ about 3 – 4 cm in length. Part of the cervix called the portio is visible on vaginal inspection.  There is a narrow canal extending from the vaginal aspect of the cervix to the endometrial cavity called the endocervical canal.  The vaginal opening to the endocervical canal is called the external os, and the opening to the endometrial cavity is called the internal os. 

The cervix is lined by two types of cells: squamous cells on the outer aspect, and columnar, glandular cells along the inner canal. The transition between squamous cells and columnar cells is an area termed the squamo-columnar junction. Most of precancerous and cancerous changes arise in this area.  Cervical cancer can arise from either of these cell types.  Squamous cell cancer is the most common type of cervical cancer (75%) and arises from the squamous cells of the outer part of the cervix. Cancer that arises from the endocervical or glandular cells is called adenocarcinoma (25%).

Symptoms

• Abnormal bleeding, particularly bleeding after intercourse, but also bleeding between periods or post menopausal bleeding

• Vaginal discharge

• Pain with intercourse

• Pelvic pain

Spread

• Local invasion to surrounding structures, including the cervix and the parametrium – the supporting tissue structures around the cervix.

• Lymph nodes, particularly the lymph nodes deep in the pelvis

• Adenocarcinomas have a slight propensity to spread to the ovaries

• To distant sites, via the bloodstream, eg lung.

• In the peritoneal (abdominal and pelvic) cavity

Risk Factors

• HPV infection

• No history of HPV vaccination

• Deficient cervical cancer screening

• Cigarette smoking

• Immunosuppression

• Multiple sexual partners and early age of first intercourse

• Intra uterine exposure to diethylstilbestrol (DES)

Diagnosis

• Clinical history and physical exam

• Cervical screening for HPV and abnormal cells

• Colposcopy (light, magnification and some special dyes to highlight abnormal areas)

• The diagnosis must always be confirmed by histological confirmation with a biopsy.  For early cervical cancer, sometimes a cone biopsy of the cervix will be required.

Treatment – Early cervical cancer

Options for surgery will depend on the reproductive requirements and age of the patient and the extent, type and profile of the tumour.  Options may include:

• Cone biopsy alone may be adequate treatment for early cervical cancer

• Simple hysterectomy

• Simple or radical trachelectomy (removal of the cervix) + removal of pelvic lymph nodes, may be feasible for some women who wish to retain reproductive capacity.

• Radical hysterectomy and removal of pelvic lymph nodes. This is currently performed via an open operation (laparotomy) after a recent clinical study showed better survival outcomes compared to a keyhole approach (laparoscopy, or robotic assisted).

• Occasionally chemo-radiation will be required in addition to surgery

Treatment – Advanced cervical cancer

• Chemo-radiation and brachytherapy

Cancer of the endometrium is a cancer of the inner lining of the uterus.  This is the part of the uterus which is shed away every month during a menstrual period in reproductive years.  This is the most common gynaecological cancer and accounts for 6% of all cancers in women.  The lifetime risk of endometrial cancer in Australia is 4%.  The majority of cases are diagnosed at an early stage and are amenable to treatment with surgery alone.  Patients with advanced stage or more aggressive types of endometrial cancer will require radiation and/or chemotherapy for optimal outcomes.

The most common type of endometrial cancer (endometrioid) is strongly associated with obesity. Our fat cells are capable of producing the hormone oestrogen and it is this excess oestrogen that causes abnormal growth of the endometrium. These types of cancers are most often early stage and low grade cancers and generally have a good prognosis. There are other types of endometrial cancer that are high grade and behave more aggressively. There has been significant progress made in the last decade in our understanding of the genetic characteristics of endometrial cancer and how this affects its growth and response to available treatments.

Symptoms

• Abnormal vaginal bleeding – especially postmenopausal bleeding, but also bleeding between periods, after sexual intercourse, or heavy and/or prolonged bleeding in reproductive aged and pre-menopausal women. Abnormal gynaecological bleeding should be considered as due to cancer until proven otherwise

• Pelvis pain

• Vaginal discharge

Spread

• Invasion into the muscle of the uterus (myometrium)

• Invasion into the cervix

• Into the peritoneal cavity

• To the lymph nodes deep in the pelvis and in front of the aorta

• Rarely, via the blood stream to distant sites such as liver and lung

Risk Factors

• Obesity

• Advancing age

• Hypertension (high blood pressure)

• Diabetes

• Hypercholesterolaemia

• Genetic predisposition eg Lynch Syndrome

• Tamoxifen therapy

• Oestrogen hormone therapy, without a counteracting progestogen

• Reproductive factors – nulliparity (no children), early menarche, late menopause, polycystic ovary syndrome.

Treatment

The most important component of treatment is the surgical removal of uterus, fallopian tubes and ovaries.  This is usually done via a laparoscopic or robotic assisted laparoscopic approach.  Occasionally, surgery will need to be performed through an open surgical approach.  Increasingly, the sentinel lymph nodes (the first and most important lymph nodes draining the uterus) will be removed to determine if the cancer has spread beyond the uterus.

Conservative Treatment

For women with many other medical issues, often associated with older age and frailty, and for women who are young and wish to conserve their reproductive capacity, there may be an option to preserve the uterus.   This usually entails the use of hormone therapy with progesterone either orally or delivered via a hormone containing intra-uterine device.  This is still considered somewhat experimental and women pursuing this option will need close monitoring.

Adjuvant Treatment

For women who after surgery are found to have tumour features associated with a higher risk of recurrence or evidence of tumour cells outside the uterus, there may be a recommendation for further treatment after surgery.  This may entail chemotherapy given every 3 weeks for 4 -6 cycles or radiation, most commonly given as external treatment (external beam pelvic radiation) over about 5 weeks. Additional chemotherapy may be given concurrently with this external radiation. Internal vaginal radiation (vaginal brachytherapy) is sometimes recommended to reduce the risk of vaginal recurrence and is delivered in short sessions over a couple of days.

Follow up

For all cancers there is some chance of the cancer coming back after treatment, and that is the reason for ongoing follow up.  As a rough rule patients are followed every 3 months for 2 years, then 6 monthly for 3 years, then some patients are followed yearly thereafter.  For patients with lower risk disease, the follow up is less intense and for a shorter duration.

Ovarian, fallopian tube and primary peritoneal cancer are best considered together because their clinical features, histological appearances and treatment are essentially identical.  The fallopian tubes, particularly the fimbrial ends sit right adjacent to the ovaries, and cancer arising in this vicinity is difficult to determine whether it started in the ovaries or the fallopian tubes.  Recent evidence suggests the most common subtype of ‘ovarian cancer’ actually indeed arises from the from the fallopian tubes.  Primary peritoneal cancer relates to cancer arising from the lining of the abdominal cavity called the peritoneum.  These cancers are actually called epithelial cancers – which arise from the lining of the ovaries, fallopian tubes and abdominal cavity, to distinguish them from less common cancer that arise from the egg cells or the stromal cells (main body) of the ovary.  Since 2000, all the big international research organizations have considered epithelial cancers arising from ovary, fallopian tube or the peritoneum as essentially one entity for trial purposes.

Risk factors

• Advancing age

• Genetic predisposition eg BRCA 1 and BRCA 2 gene mutations

• Strong family history

• Nulliparity

• Infertility

• Oral contraceptive pill, higher parity and breastfeeding – all protective against ovarian and related cancers.

Symptoms

Ovarian and related cancers notoriously cause few symptoms till the disease is quite advanced, and the earliest symptoms are often subtle and vague.  Symptoms include:

• Abdominal distension or a feeling of pressure in the abdomen

• Abdominal or pelvic pain

• Awareness of a mass in the belly or rising out of the pelvis

• Disrupted bowel function, especially constipation

• Disrupted menstrual function

• Occasionally vaginal discharge or bleeding.

Spread

• Adjacent organs – ovary, fallopian tube and pelvis

• Throughout the peritoneal (abdominal) cavity

• The fluid around the lungs

• Lymph nodes in the pelvis, abdomen, chest and groin

• Via the blood stream to distant sites

Treatment of early stage ovarian cancer

For women who have completed their family, treatment entails surgery to remove uterus, fallopian tubes and ovaries (TAHBSO) + staging.  Staging refers to the removal or biopsy of places where the cancer has a propensity to spread – peritoneal surfaces, fluid around the pelvic organs, lymph nodes, omentum and the appendix.  If the cancer is localized to the ovary and is of low grade (low aggressiveness), chemotherapy may not be required.  Under all other circumstances, chemotherapy is administered to give optimal outcomes.

In uncommon circumstances, for women with early stage disease and wishing to retain reproductive capacity, it may be possible to retain the uterus and the other ovary, while undergoing all other aspects of the staging surgery.  Chemotherapy may or may not be required and typically the reproductive organs are removed at the completion of child bearing.

Treatment of advanced stage disease.

For many years the gold standard treatment for ovarian and related cancers has been to attempt to surgically remove all or as much visible disease as possible and then follow this with chemotherapy.  Surgery can be quite extensive including removal of uterus, tubes, ovaries, omentum and on occasion parts of the bowel, stomach, and the liver, the spleen, the lymph glands and stripping of the peritoneal lining of the abdomen that contains disease.  The goal of surgery is really to remove all visible evidence of tumour.

Recent studies have shown that for patients with very advanced disease, by giving 3 cycles of chemotherapy prior to the surgery (so called neoadjuvant chemotherapy), patient’s general medical condition improves and the extent and burden of cancer reduces.  The studies show that this approach is associated with a reduction in complications and death related to surgery, an increased likelihood of removing all macroscopic disease and no reduction in overall survival from the disease.  The decision to have primary surgery or neoadjuvant chemotherapy will be determined by the treating gynaecologic oncologist based on CT scan findings and the general condition of the patient.

Chemotherapy

The administration of chemotherapy takes place in specialised units under the supervision of a medical oncologist.  These sub-specialty trained clinicians determine the type and dose of chemotherapy, monitor and manage side effects and provide ongoing clinical review.

Genetic and tumour testing

The most common type of epithelial ovarian cancer (high grade serous) may be caused by an inherited abnormality (mutation) in a BRCA gene in around 15% of cases. It may also be due to a spontaneous mutation in a BRCA gene in the tumour itself in a further 10% of cases. There may be other mutations in the tumour that cause similar effects to a BRCA mutation called “homologous recombination deficiency” in a further 25% of cases.

Germline (genetic testing, typically a blood test) and Tumour tissue testing for patients with high grade epithelial ovarian cancer is recommended for several reasons. If a hereditary or inherited (germline) mutation is shown, it may place the patient at risk of other cancers, and their family members may also be at risk of having the mutation. If a germline or tumour (somatic) mutation is shown, it may enable access to further treatment options such as a PARP inhibitor (eg Lynparza/Olaparib).

Follow up

Follow up of ovarian cancer is usually shared between the gynaecological oncologist and the medical oncologist (chemotherapy doctor).  Follow up is at 2 – 3 monthly intervals for the first 2 – 3 years and then longer intervals between visits at the discretion of the treating doctors.

Vulva cancer accounts for about 5% of gynaecological cancers.  Vulval cancers often cause itch or pain and as the vulva is an external organ, an skin abnormality such as a lump or growth will usually be visible or felt.  Vulval cancers are often a hard ulcer or lump, but can be more subtle skin change and arise in background abnormal vulval skin conditions called vulvar intra-epithelial neoplasia (VIN) or lichen sclerosus. 

Any vulval symptoms or concerns about a vulval abnormality should be discussed with your doctor. An examination should be performed and on-referral to a specialist if there are concerns or any uncertainty around a diagnosis. Unfortunately the diagnosis of this cancer is often delayed due to these steps not being followed.

Symptoms

• Itch – this is an almost invariable symptom in women with early vulvar cancer and should not be ignored

• Lump

• Bleeding

• Pain

• Ulceration

Spread

• Local invasion into surrounding tissues

• Via lymphatics to groin lymph nodes

• Rarely via the blood stream to distant sites.

Risk Factors

• HPV (Human papilloma virus)

• Lichen sclerosus

• Vulvar Intra-epithelial neoplasia (VIN) – either associated with HPV infection, or a condition called differentiated VIN, associated with lichen sclerosus. VIN is a pre-cancerous condition and needs treatment

• Cigarette smoking

• Immunosuppression

Treatment

The cornerstone of treatment is surgery.  The aim of surgery is for radical excision or clearance around the cancer, with the depth of surgery taken down to the deep fascia.  Depending on the size and depth of the cancer, lymph glands may need to be taken from either or both groins.  If the cancer is less than 4 cm and there are no suspicious lymph nodes, consideration will be given to removal of the sentinel lymph node (the most important node draining the site of the cancer).

Under some circumstances radiation may be used in the treatment.  This would be where the cancer is so close to the urethra or anus that surgical treatment would compromise bladder or rectal continence.  Sometimes radiation is used to treat small cancers of the clitoris to preserve that organ and radiation may be used where there are involved lymph nodes in the groins.

Lifelong treatment with high potency steroid ointment to the vulval skin is recommended for lichen sclerosus to reduce the risk of vulval cancer.

Follow up

As with the follow up of most gynaecological cancers, the follow up is typically every 3 months for the first 2 years and then 6 monthly for the following 3 years and then annually thereafter.

• Cancer Australia

• Cancer Australia

From epidemiological research it is apparent that some families have high rates (or clusters) of members with either breast or ovarian cancer, or sometimes both.  This has become known as Hereditary Breast-Ovarian Cancer (HBOC).  With advances in molecular genetics, we have come to recognise abnormalities or mutations in certain genes associated with HBOC.  The two most common are mutations in genes called BRCA1 (located on chromosome 17) and BRCA2 (located on chromosome 13).  There are other lesser known and rarer genes such as BRIP1 and RAD51C which are also associated with HBOC.  With time and further advances in molecular genetics, it is likely that we will have a more complete picture or library of genetic mutations associated with HBOC.

BRCA1 gene mutations are associated with up to an 87% lifetime risk of breast cancer and an 63% lifetime risk of ovarian cancer.  The risk of these diseases typically escalates from the age of 35-40.  BRCA2 gene mutations are associated with up to an 84% lifetime risk of breast cancer and up to a 27% lifetime risk of ovarian cancer.  Typically, the risk of these diseases escalates from the age of 40-45. 

The diagnosis of a BRCA gene mutation has traditionally been initiated by establishing a family tree or pedigree.  This can be inaccurate or misleading in up to 50% of true HBOC families sometimes reflecting small family size, adoption or other issues.  Formal genetic testing has traditionally been recommended when there is a greater than 10% risk of carrying a BRCA1 or 2 mutation.  This involves consultation with a clinical geneticist and either a blood or saliva test.  It is available through Genetic Health Queensland for no cost (strict eligibility criteria apply) or privately for about $600.

The advantages of genetic testing include:

• The opportunity for more intense screening of breast cancer +/- risk reducing surgery.

• The opportunity for risk reducing surgery for ovarian cancer.

• Valuable information for other family members.

• Tailored treatment of patients with established disease. Cancers that demonstrate the BRCA mutation respond well to newer treatments including the so-called PARP inhibitors.  About 15% of ovarian cancers are associated with an inherited BRCA mutation and another 10% will have a mutation just in the cancerous tumour tissue.

Unfortunately, there is no effective screening test for ovarian cancer, even in high risk populations like HBOC.  A recently published very large research trial found that screening for ovarian cancer with ultrasound and blood testing for CA125 resulted in some women being diagnosed with ovarian cancer at an earlier stage, but unfortunately this did not translate into less women dying from their cancer. The oral contraceptive pill may mitigate the risk somewhat in reproductive aged women.  On a more positive note, there is very good evidence that risk reducing surgery significantly reduces the risk of ovarian cancer and improves survival in at-risk groups.  Risk reducing surgery usually involves either removal of fallopian tubes and ovaries (BSO) or more typically removal of uterus, tubes and ovaries (THBSO).  These operations are nearly always performed via a laparoscopic (keyhole) approach and should typically be performed by a gynaecological oncologist.

The timing of preventive surgery depends upon completion of family, and it is usually recommended that such surgery is undertaken at least 5(-10) years before the age at which other family members may have been diagnosed with disease.  For BRCA2 mutation carriers, surgery from age 40-45 is often recommended, and from 35-40 for BRCA1 mutation carriers.  Risk reducing surgery is certainly recommended for post-menopausal women. When both ovaries are removed in reproductive age women, this will cause menopause.  There are several options for managing this depending on the type and extent of surgery and other medical diagnoses.  These are important issues to consider and discuss when contemplating risk reducing surgery.

Sometimes there are well-meaning recommendations in the lay press about being “vigilant” for symptoms of early ovarian cancer.  Sadly, by the time people have symptoms, 75% will be diagnosed with advanced disease (stage 3 and 4).  This illustrates why risk reducing surgery is of value – there is no effective screening test and the disease most typically is quite advanced by the time there are symptoms.  While survival from ovarian cancer has increased over the last 2 decades, there is no doubt that “prevention is better than cure”.