Gynaecologists will be asked to manage women with a pre-invasive disease of the vulva at some point in time. It is essential that we are familiar not only with these conditions, but also with the potential pitfalls of assessment and treatment.
The two main pre-invasive conditions of the vulva are vulvar intraepithelial neoplasia (VIN) and, to a lesser degree, extra-mammary Paget’s disease. These conditions are uncommon. However, there is evidence supporting an increased frequency of VIN. Over the last 30 years, there has been a reported 400 per cent increase in the incidence of the disease, especially in young women.1 All gynaecologists will be asked to manage women with these conditions at some point in their career. There are four basic steps to avoid problems associated with diagnosis and treatment.
The first two of these steps are to establish the diagnosis and determine the extent of the disease before commencing treatment. This may sound obvious, but these steps are not uncommonly overlooked, which results in suboptimal care.
Most women with preinvasive disease of the vulva will have seen their general practitioner with long-standing symptoms such as pruritus, burning sensation, pain and dysuria. They may have noticed a lump or change in pigmentation of the vulvar skin. Occasionally, an asymptomatic lesion will be noticed by the GP at the time of an examination for some other reason. Delay in diagnosis is unfortunately common, as symptoms are often thought to be due to thrush. Frequently, women will have been treated with a variety of topical steroids and antifungal preparations with limited success.
Usually the diagnosis has not been made prior to the consultation with the gynaecologist. Therefore careful colposcopic examination, with application of five per cent acetic acid, of the entire lower genital tract, including the perianal skin, is essential. In younger patients, vulvar intraepithelial neoplasia is more likely to be multifocal, more extensive and human papilloma virus (HPV) related. In contrast, older women usually have more localised disease often arising in a background of lichen sclerosis (LS).2 Biopsy is mandatory to establish a diagnosis. At times multiple biopsies may be required to determine the extent of the disease and to exclude occult invasion prior to treatment. In younger women, vulvar intraepithelial neoplasia and cancer may appear warty and be misdiagnosed as condylomata accuminata. In older women with chronic untreated LS, the entire vulva may appear abnormal and it can be difficult to determine the worst area. Cancer, if present, may be obvious, but occult invasion is difficult to determine clinically.
Paget’s disease of the vulva has an eczematoid appearance. In the author’s experience, however, it can be very subtle. This highlights the importance of histopathology prior to commencing treatment, especially in women with persistent symptoms who have not responded to the usual gamut of medical therapies.
The aims of treatment
The aims of treatment need to be considered, including:
- control of symptoms;
- preventing the progression to invasive cancer;
- preventing recurrence of the condition; and
- preserving as much normal vulvar anatomy and function as possible.
Keeping the aims of treatment in mind helps to set the foundations of treatment. For example, an elderly woman with 30 years of symptoms due to lichen sclerosis who then develops VIN may not object to more extensive surgery if there is a reasonable chance that her symptoms will improve and it reduces her risk of developing cancer, even if the clitoris is removed. Other options may need to be considered in younger women. The natural history of vulvar intraepithelial neoplasia will never be completely understood, but it is thought the risk of progression to cancer occurs in about four per cent of treated cases and up to 87.5 per cent of untreated cases.4
Treatment needs to be individualised
Finally, treatment options need to be considered. No one treatment modality is ideal for every patient and therapy should be individualised based upon the patient’s diagnosis, age and comorbidities, the position and size of the lesion/s and the condition of the remaining vulvar skin.
Treatment options include surgical excision, carbon dioxide laser and Imiquimod cream. Surgical resection is the author’s preferred option as it removes the lesion and allows histopathological assessment of the surgical margins, but also excludes occult invasive carcinoma. This is more relevant in older women. For VIN, a surgical margin of 5mm is considered reasonable, but it should be remembered that the lesion may extend beyond the visible margin.5
Primary closure is usually possible with small lesions where there is some mobility of the surrounding skin. However, where there would be excessive tension or the cosmetic/functional result would be inferior, a flap repair should be considered. A number of flap procedures have been described, but are beyond the scope of this article. In general, the ideal flap not only fills the resection defect, but also allows easy closure of the donor site.
Wound breakdown and delayed healing are recognised complications of treatment.4 The best way to avoid this problem postoperatively is to ensure a tension-free wound at the time of surgery. Patients should also be given advice postoperatively to minimise physical activity for about three to four weeks. Depending upon the size of the defect after resection, the patient and the experience of the gynaecologist, consultation with a plastic surgeon may be appropriate.
Carbon dioxide laser ablation is used widely with similar recurrence rates. It is particularly useful in lesions close to, or involving, the clitoris and/or external urethral meatus. Some consider laser to be the treatment of choice, especially for young women.3 Very large lesions can be extremely painful after laser ablation and patients need to be warned of this. In addition, it is important to rule out invasive cancer prior to commencing this therapy. Care should be taken using any ablative treatments in those women past the menopause because they are at higher risk of squamous cell carcinoma (SCC) at diagnosis.2
Aldara Cream (five per cent Imiquimod), a topical immune response modifier, has been used increasingly in women with vulvar intraepithelial neoplasia and there is evidence for its efficacy, especially in young women with HPV-related disease. As is the case with other treatment modalities, it is more efficacious with small lesions. It also preserves vulvar anatomy. Response rates of up to 64 per cent have been reported. However, about 25 per cent will have limited response and require additional ablative or surgical resection. Recurrence rates of 25 per cent have been reported.6 Care must be taken to exclude invasive cancer before using this option.
Consent is an essential part of the therapy. Surgery on the vulva can result in significant anatomical distortion and psychosexual dysfunction. The extent of any procedure needs to be explained clearly. It is essential to work out what the patient understands about their procedure, especially if there will be loss of the clitoris and/or labia minora. The clinician cannot assume the woman understands her external genital anatomy and she may not fully comprehend what is being treated or removed. Nor can it be assumed a woman has ceased sexual activity based upon her age. A sexual history is important in developing treatment options and ensuring women consent to the side effects of treatment.
The loss of the labia minora can also result in spraying of urine on to the inner thighs rather than in a directed stream. This can be an awkward side effect of surgery. Some women will go on to develop a dermatosis from chronic exposure to urine, very similar to ‘nappy rash’.
It is reasonable to also warn patients of the possibility of recurrence. This is more likely if surgical margins are involved and further treatment may be required. However, provided the macroscopic lesion is completely removed, further surgical excision is usually not warranted in the short term. In the event that a malignancy is detected, the initial step would be to, at least, discuss the case with a gynaecologic oncologist and have the pathology reviewed to determine if any further treatment is required.
Patients require follow up
Recurrence rates of VIN in the order of 15–50 per cent have been reported.2 Accordingly, women who have been treated will require follow up. However, there are no evidence-based guidelines as to what constitutes appropriate surveillance. It is the author’s practice to colposcopically examine women every six months for two years and then yearly up to five years after treatment, depending upon the age of the patient and condition of the remainder of the vulva. For example, a young woman with a localised lesion that has been fully excised is at lower risk of recurrence than an older woman with extensive LS. There is evidence to suggest older women are at increased risk of recurrence.2
Women who are immunosuppressed are at higher risk of HPV-related disease of the lower genital tract. Long-term steroid use and immunosuppressents used in organ transplant recipients are the more common contributing factors; however, women with HIV infection or some forms of congenital immunodeficiency syndrome remain at risk of developing preinvasive disease and cancer. These women may actually have a ‘field’ defect with disease involving the cervix, vagina, vulva and perianal skin. Close, life-long follow up is required in these women.
In summary, preinvasive disease of the vulva can be difficult to manage. Care must be taken as, not surprisingly, patients are often anxious and frustrated. They need adequate counselling (sometimes formally with a psychologist) and preparation. Treatment should be individualised with an aim to not only treat the disease, but also preserve as much normal vulva as possible. Developing adequate skills to manage these problems is difficult due to their infrequent presentations.