In females, the external genitalia are referred to collectively as the vulva. The vulva includes the labia majora (large lips), the labia minora (small lips), the clitoris, the mons pubis and the perineum. The inner area between the labia minora is called the vulvar vestibule, which surrounds the openings of the vagina and urethra. Near the back of the vulvar vestibule are openings of the Bartholin’s glands, as shown in the diagram. The vulva is covered by skin, which has an outer layer of squamous epithelium and some underlying glands.
The skin of the vulva and the lining of the vagina both have a relatively rich blood supply and lymphatic drainage. The lymph channels from the vulva pass to the groin, while those from the vagina pass mainly to the lymph nodes in the pelvis.
Cancer of the vulva is uncommon, accounting for only about 4% of gynaecological cancers. Ninety percent of the cancers arise from the skin surface (squamous cell carcinomas), but cancer can also arise in glands under the skin (adenocarcinomas). Melanomas occasionally occur on the vulva.
The average age at the time of diagnosis is 65 years.
Table 1. New cases of Vulvar Cancer in Australia, 2003-2008
|Type||Under 30 yrs||30-49 yrs||50-69 yrs||70 and over|
Vulvar melanoma is the second most common vulvar cancer, typically affecting post-menopausal women. They are classified as mucosal melanomas. In Australia, only about 10 women are diagnosed each year (one in a million) compared with over 4700 women who are diagnosed with a typical skin melanoma (cutaneous melanoma). In a recently published review of 33 women treated in 2 Australian hospitals in the past 3 decades, the average age at diagnosis was 67 years. Most melanomas were found on the labia minora.
Vulvar melanomas are commonly diagnosed at a late stage, when they may have spread to other areas. In the Australian study, the women usually became aware of the pigmented lump themselves, but they typically delayed reporting it to their doctor for 2 years. In some cases, the delay was up to 10 years. By contrast, campaigns to increase awareness of cutaneous melanomas have meant that many of these are now diagnosed at an early stage, before they have spread.
The cause of vulvar melanoma is poorly understood. They are not related to sun exposure and gene mutations that are important in cutaneous melanomas have not been found in vulvar melanomas, indicating that these two melanomas are caused by different factors.
Any locally pigmented area on a woman’s vulva should be regarded as suspicious and it is usually advisable to excise the area and have it examined by a pathologist. Most likely it will be a benign naevus, but if a malignant melanoma is diagnosed, it should be more widely excised. Following on the trend from cutaneous melanomas, the surgical approach for vulvar melanomas has changed from extensive removal of the vulva (radical vulvectomy) to removing only the tumour with 1 cm margins (radical local excision). It is now recognized that more extensive surgery does not improve survival.
Consideration should also be given to removal of the groin lymph nodes, with or without the guidance of sentinel node biopsy, if the depth of invasion is more than 1 mm. For melanomas, depth is a better guide to treatment. The standard FIGO staging, as used for squamous cell carcinoma, is not satisfactory for melanomas because even quite small melanomas can invade deeply and spread to lymph nodes and other parts of the body.
Treatment of women with advanced disease has had disappointing results. Radiotherapy, chemotherapy, immunotherapy and targeted therapy have all been tried with limited success.
Because they are often diagnosed late and treatment options are limited, the overall 5-year survival rate for women with vulvar melanomas is only about 30%. A woman with a thin melanoma (invasion depth less than 1 mm) has almost a 100% chance of long term survival. The prognosis gets worse as the invasion gets deeper.
Paget’s disease usually affects the nipple area of the breast, but can occasionally affect the vulva. When the disease affects the breast, there is usually an underlying invasive cancer.
Vulvar Paget’s disease is usually a glandular type of precancer (adenocarcinoma in situ) and only about 20% of cases have an associated underlying invasive cancer (adenocarcinoma). The invasive cancer usually arises in the vulva, but may occasionally arise in local organs such as the bladder, urethra, or rectum.
A woman with Paget’s disease is likely to be postmenopausal. She will usually report itching and tenderness, which may be long-standing. The appearance can be confused with other “rashes” on the vulva and a biopsy should be taken to confirm the diagnosis. She should have a colonoscopy to check the bowel if she has Paget’s disease near the anus and/or cystoscopy to check the bladder if she has Paget’s disease around the outlet of the urethra.
All visible disease should be widely excised (wide superficial local excision). The disease will often recur and multiple excisions may be necessary over many years. If left untreated, Paget’s disease may spread like a rash well beyond the vulva to the mons pubis, thighs, rectum, vagina, or urinary tract.
If there is an associated underlying cancer present, it can spread to lymph nodes in the groin, so the disease should be treated like a squamous cell cancer of the vulva. This means excising the cancer more deeply (radical local excision) and resecting the groin lymph nodes on the affected side or sides (inguinal-femoral lymphadenectomy).
Squamous Cell Carcinoma
There are two different types of vulvar cancer. The most common form occurs in postmenopausal women and is usually associated with a long history of chronic vulvar itching. The most likely cause of the itching will be a skin condition called lichen sclerosus, which affects around one in 80 women. Lichen sclerosus can occur at any age, including children, but is most common in middle-aged and elderly women. In most cases, it is a lifelong affliction. It can be managed by using cortisone cream to minimise the itching, but it needs to be carefully observed. The chance of lichen sclerosus progressing to vulvar cancer is probably in the order of about 5%.
The less common type of vulvar cancer occurs in premenopausal women. It is likely to be associated with smoking and with persistent, sexually acquired infection with the human papilloma virus (HPV). Chronic HPV infection can cause a precancerous condition called vulvar intraepithelial neoplasia (VIN), which also causes itching or burning. If VIN is not identified and treated, the risk of progression to vulvar cancer may be at least 30%. This is similar to the way chronic HPV infection affects the cervix and vagina. VIN can be treated by localised surgical excision or laser therapy, neither of which is likely to cause significant scarring.
Immunosuppression is another important factor. This typically occurs after long term cortisone or methotrexate treatment of a woman who has a chronic autoimmune disorder or who has had an organ transplant. It will reduce the woman’s resistance to viral infection and cancer, making VIN and vulvar cancer more likely.
HPV vaccination for schoolgirls was introduced in Australia in 2007 and recently extended to cover schoolboys. This strategy has already lowered rates of precancers of the cervix in younger women and will progressively decrease the rates of vulvar and vaginal cancer in the future.
A woman with vulvar cancer is most likely to become aware of a vulvar lump, usually on her labia majora, but possibly on her labia minora, clitoris, or the area in front of her anus (perineum). She will usually have had a long standing history of vulvar itching. The lump may be raised above the skin or it may be ulcerated.
Occasionally, the woman may become aware of a lump in her groin. This is usually, but not always, an indication that the cancer has spread to the lymph nodes in the groin.
A small piece of the lump should be taken (a biopsy) and sent to the pathologist for examination under the microscope. A biopsy can usually be done in the clinic under local anaesthesia.
Although vulvar cancer starts as a small lump or ulcer, if it is not diagnosed and treated it will continue to grow and progressively spread into nearby organs such as the vagina, urethra and anus. It can also spread fairly early to the lymph nodes in the groin. About 30% of vulvar cancers will have involvement of lymph nodes in the groin.
Only when the cancer has been present for a long time will it enter the blood stream and spread to distant organs such as the lungs, liver and bone.
Squamous cell carcinomas are staged according to the guidelines of the International Federation of Gynaecology and Obstetrics (FIGO). A summary of the main stages is as follows:
Stage 1 means the cancer is confined to the vulva.
Stage 2 means the cancer has spread to the lower vagina, lower urethra, or anus.
Stage 3 means the cancer has spread to the groin lymph nodes.
Stage 4 means the cancer has spread to distant organs, such as lungs, liver, upper urethra, bladder, or rectum.
Traditional treatment for vulvar cancer has included removal of the entire vulva (radical vulvectomy). This surgery is associated with significant psychological distress, similar to that experienced by a woman after removal of her breast (radical mastectomy). Over the past 3 decades, the surgery for early breast cancer has become much more conservative, with preservation of as much breast tissue as possible and so too has the treatment of early vulvar cancer.
Modern treatment for early vulvar cancer requires a wide excision of the cancer (radical local excision), with preservation of as much of the normal vulva as possible. If a woman’s small cancer has invaded very superficially (less than 1mm), there is no need to remove the lymph nodes, but if invasion is deeper she should have removal of the lymph nodes in her groin (inguino-femoral lymphadenectomy). It is usual to only remove the lymph nodes on the same side as the cancer, unless the cancer is in the midline, such as a cancer of the clitoris, or perineum. Much of the normal vulva can be preserved, unless the cancer is very large, or present in multiple different sites (multifocal)
The surgical specimen is sent to the pathologist and checked under the microscope to ensure that cancer is well clear of the edge of the specimen. The lymph nodes are also carefully examined under the microscope. If cancer is found in the nodes (i.e. if there are lymph node metastases), she may need to receive radiation therapy to the groins and pelvis.
If the cancer is more advanced and involves the anus or upper vagina, initial treatment with radiation therapy will usually be the best approach, shrinking the tumour and allowing a more limited operation.
Removal of the lymph nodes from a groin causes swelling of the leg (lymphoedema) in about 50% of cases. This swelling usually occurs 6-12 months after the operation. If lymphedema develops, it is a lifelong problem and will require massage from a physiotherapist and use of a surgical stocking to control the swelling.
A woman who has had her groin nodes removed should be counselled about ways to decrease the risk of developing lymphoedema. It is important to avoid any cuts or scratches to the leg, because these may get infected very easily and the infection (cellulitis) may precipitate the onset of lymphoedema. Support stockings should also be worn on aeroplane flights, because flights can sometimes be a precipitating factor.
In order to decrease the risk of lymphoedema, some gynaecological oncologists recommend sentinel lymph node biopsy. The sentinel node is considered to be the first node involved when the cancer spreads to the groin. It may be identified by injecting a blue dye and a radioactive substance around the cancer, then locating and removing the blue, radioactive node in the groin. If it contains no cancer, the strategy is to leave the remainder of the nodes in the groin.
Although sentinel node biopsy is an attractive theory, in practice not all positive nodes will be identified. A small number of women having sentinel node biopsy will die from cancer in the groin who would have been most likely cured treated by inguino-femoral lymphadenectomy. It is important that women understand the risks and benefits of the different approaches. Most, but not all, women would prefer to live with any lymphoedema they may develop rather than take a small additional risk of dying with recurrent vulvar cancer.
The overall outlook for a woman diagnosed with squamous cell vulvar cancer is good, the 5-year survival being about 70%. Some of these cancers tend to recur many years later, often after starting as a precancer, so it is important she continues to see her cancer specialist every year for the rest of her life.