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Abstract
- Ovarian cancer is a key differential diagnosis in any woman presenting with vague abdominal symptoms such as bloating, urinary or gastrointestinal changes. Ovarian cancer is linked to the BRCA1 and 2 gene mutations. This means that it is important to be wary of any symptoms of ovarian cancer in patients with those mutations.
- There are three main types of ovarian cancer depending on the cell line that the cancer originates from: epithelial, germ cell and sex cord stromal. Each of these types has many subtypes, all of which are treated differently.
- The uterus has two main tissue types that can turn cancerous: the myometrium (which forms benign fibroids, also known as leiomyomas) and the endometrium (which forms malignant adenocarcinomas).
- Cell division in the uterus is driven by the hormone oestrogen. Therefore, any unopposed oestrogen increases the chance of developing either of these conditions. The mainstay of curative management of uterine cancer currently is surgical removal.
- The cervix is the opening and junction between the uterus and the vagina. It has two different cell types: the stratified squamous epithelium on the vaginal opening, and columnar epithelium on the uterine, with the transition zone in between. It is most common for precancerous cells to appear on the transition zone due to the change of cell type here.
- HPV strains 16 and 18 are associated with almost all cases of cervical cancer (as well as contributing toward risk of oral, vulval, anal and penile cancer), and so is vaccinated against in all 12-13 year olds in the UK.
- The UK also has a cervical cancer screening program, where women between 25-49 are offered a smear every 3 years, and between 50-64 every 5 years. This helps to detect potentially precancerous changes (called Cervical Intraepithelial Neoplasia) before they develop into cancer.
- The vulva is part of the external genitalia of women, and is covered by squamous epithelium, making the most common cancer of this organ squamous cell carcinoma. Risk factors for development include HPV 16/18 infection and lichen sclerosis, a chronic inflammatory condition of the vulva.
Core
This article focuses on cancers of the female reproductive tract, and so includes information on cancers of the vulva, cervix, uterus and ovaries.
For information on cancers of the male reproductive tract (including prostate and testicular), see our article here.
For information on cancers of the breast, see our article here.
Ovarian cancer is a cancer which is infamously hard to detect. Ovarian cancer is usually associated with only very vague abdominal symptoms such as bloating, distension, abdominal pain, urinary or gastrointestinal changes (e.g. constipation or urinary urgency), and hormonal disturbances. As many of these symptoms may be mild, misdiagnosed as irritable bowel syndrome or gastroenteritis, or not assumed to be associated with one another, ovarian cancer commonly goes undiagnosed and as a result is usually in later stages on detection.
Ovarian cancer is associated with mutations in the BRCA1 and BRCA2 genes both of which are also associated with breast cancer. As a result any patients with known gene mutations presenting with the vague abdominal symptoms mentioned above should be investigated for ovarian cancer with a high level of suspicion.
CA-125 is a tumour marker which is measured via a blood test if ovarian cancer is suspected as it can be raised in this condition. CA-125 can be a sign of ovarian cancer or other neoplastic and non-neoplastic conditions including - endometriosis, fibroids and even pregnancy. CA-125 may also be normal in early stages of ovarian cancer, so a normal result does not exclude disease and further assessment, including imaging, may be required.
Remembering the lymphatic drainage of the ovaries is important when removing ovarian masses. Lymphatic drainage of the ovaries is to the para-aortic lymph nodes.
There are three main cell lines in the ovaries, and therefore three possible origins of cancer that can occur in the ovaries. There are many subtypes beyond the scope of this article so only the main subtypes are discussed here.
Epithelial ovarian cancer is the most common type of ovarian cancer. It stems from the epithelial covering of the ovary and are carcinomas.
There are multiple subtypes:
- Serous - the most common subtype and primarily cystic in nature.
- Endometrioid
- Mucinous
Cancer of the epithelium of the fallopian tubes is similar to epithelial cancer of the ovaries.
Germ cell tumours of the ovary stem from the ova (egg cells) present in the ovary, and can be benign or malignant. They occur most commonly before the age of 30.
There are multiple subtypes:
- Benign - teratomas (often called dermoid cysts). The mature subtype of these tumours can differentiate into multiple tissue types so may contain structures such as teeth and hair.
- Malignant:
- Yolk sac tumours
- Choriocarcinomas - these are tumours derived from placental-type cells.
Sex Cord Stromal (Ovarian stromal)
Sex cord stromal tumours are derived from the granulosa and theca interna cells that exist to support the ovum.
The uterus is a secondary sex organ - this means that it matures only once puberty has begun. Anatomically, it is made up of the fundus (superior) and body. It has two main components:
The myometrium is the smooth muscle layer of the uterus which is used to expel the fetus during labour or the menstrual blood during a period.
Fibroids (also known as leiomyomas) are common, benign, well circumscribed tumours that are oestrogen dependent, this means they enlarge during pregnancy and with use of oestrogen-containing contraceptives, and that they regress following the menopause. They are normally asymptomatic, unless large, when they may present with menorrhagia, urinary frequency, pelvic pain and fertility issues.
Malignant tumours of the myometrium such as leiomyosarcoma are possible, but rare.
Endometrial cancer is the commonest gynaecological cancer in the UK (source), and has peak incidence in post-menopausal women. It is an adenocarcinoma (derived from glandular tissue), and is responsive to oestrogen, meaning that circumstances which increase oestrogen exposure (such as early menarche, late menopause, tamoxifen use or oestrogen only hormone replacement therapy) increase the risk of developing endometrial cancer.
The presentation of endometrial cancer is normally abnormal bleeding patterns, typically intermenstrual or, due to the commoner ages of presentation, post-menopausal bleeding. If it is suspected, it can be investigated with an ultrasound scan. A thickened endometrium warrants further investigation.
Treatment of endometrial cancer is commonly by hysterectomy. In pre-menopausal women, other efforts can be made to preserve fertility if the patient’s family is not complete.
The cervix is the point of connection between the vaginal canal and the uterus. It is made up of two regions: the endocervix and the ectocervix.
The ectocervix is the portion of the cervix that extends into the vagina. It has a stratified squamous (non-keratinised) epithelium. The opening of the ectocervix is called the external os.
The endocervix (endocervical canal), is the inner part of the cervix, between the external os (vaginal end) and internal os (uterine end). It is lined by simple columnar epithelium that secretes cervical mucus.
These two cell lines mean that cervical cancers can be squamous cell carcinomas or adenocarcinoma (of the mucus producing cells).
The join between the stratified squamous epithelium of the ectocervix and the columnar epithelium of the endocervix is called the transformation zone. This point is of extra concern in the development of cancers.
Lesions called cervical intraepithelial neoplasia (CIN) can be a pre-malignant lesion, meaning that without treatment, they will progress to cervical neoplasia. These cells can be detected on cervical smears, meaning that pre-cancerous lesions can be detected before cancer has set in.
The human papillomavirus is a virus that infects the skin, commonly of the genitals, mouth or anus. Most infections are asymptomatic. Some strains of HPV can cause genital warts (strains 6 and 11) and some strains can predispose to cancers including cervical, vulval, penile, anal and oral (strains 16 and 18). Approximately 99% of cervical cancers are associated with HPV infection, with strains 16 or 18 being associated with over 70% (source).
In the UK, 12-13 year old males and females are routinely offered the HPV vaccine, which protects against multiple high-risk and wart-associated strains, including 6, 11, 16 and 18. This helps to reduce the incidence of cancers associated with HPV infection and the incidence of genital warts.
In the UK, cervical screening is offered to all females between the ages of 25-49 every 3 years, and between the ages of 50-64 every 5 years.
During the examination, a small sample of cells is taken from the cervix and first tested for HPV. If HPV is detected, the sample is then examined with cytology to look for abnormal cells. This checks for any abnormalities in the cells which are pre-malignant (CIN).
If the sample is found to be HPV negative, there is low risk of cervical cancer and the patient would be invited for another regular screening based on their age (either 3 or 5 years later).
If the sample is found to be HPV positive, but there are no abnormal cells found, the risk of cervical cancer is increased slightly. This patient would be invited for another screening in 1 year.
If the sample is found to be HPV positive and there are abnormal cells found, the risk of cervical cancer is high. This patient would be invited for a colposcopy (visualisation of the cervix) to further investigate the abnormalities. At colposcopy, the patient may undergo further biopsy or procedures to remove the abnormal cells to help prevent them progressing into cancer.
The vulva is the external genitalia of a woman, made up of the labia majora, labia minora and clitoris. Like any other skin on the body, it has a keratinised squamous epithelium to help the skin resist damage with any friction, meaning that most of the cancers that occur in the vulval region are squamous cell carcinomas. However, because it is skin, malignant melanomas or basal cell carcinomas can also occur.
As with all cancers, risks for development include anything that causes chronic inflammation, such as lichen sclerosus. This condition does not have a known cause, but results in the development of white patches of itchy, cracked skin. As this occurs in the genital area, the skin can split and heal repeatedly, resulting in chronic inflammation and an increased risk of developing vulval cancer.
Another risk factor for vulval cancer is HPV infection, specifically strains 16 and 18. These are the strains associated with cervical cancer, and cause vulval intraepithelial neoplasia in a similar way to the development of cervical intraepithelial neoplasia.
It is important to note that HPV strains 6 and 11, which cause genital warts, are not directly associated with the development of carcinomas.
The management of vulval cancer involves local excision and lymph node removal (superficial inguinal). If the cancer has spread, it will commonly have invaded locally, into structures such as the anus, vagina or bladder.
Edited by: Dr. Ben Appleby
Reviewed by: Dr. Thomas Burnell
In this article
Ovarian cancer is a key differential diagnosis in any woman presenting with vague abdominal symptoms such as bloating, urinary or gastrointestinal changes.
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