Vulvar Intraepithelial Neoplasia: Aspects of the Natural History and Outcome in 405 Women

From 1962 to 2003, 405 women with vulvar intraepithelial neoplasia (VIN) 2–3 were seen in the vulvar clinic of the National Women's Hospital in Auckland, New Zealand. This paper presents an analysis of the clinical characteristics and outcomes after surgical treatment of this series of patients. A few women received no treatment, and the clinical course of their disease is also presented. All diagnoses were made according to the histologic criteria and revised terminology of the International Society of Vulvovaginal Disease. All patients had histologically diagnosed VIN. To avoid including women with unidentified invasive cancer, women with an original diagnosis of VIN who were subsequently diagnosed with invasive vulvar cancer within 1 year were excluded. From 1962 to 1979, the mean age of patients in this series was 50 years; since 1980, the mean age has dropped to 39 years with 79% of patients under 50 years of age at the time of diagnosis. The ethnic background of the 405 women corresponded to contemporary ethnic populations. Eighty-four percent of patients were smokers at the time of diagnosis. One hundred seventy-three women had a history of some form of sexually transmitted infection, including 138 (34%) with genital condyloma. Five patients were positive for human immunodeficiency virus. A history of treatment for cervical intraepithelial neoplasia 2 or 3 was obtained from 112 patients, and 17 had been treated for vaginal intraepithelial neoplasia. Another 17 women had been treated for cervical invasive cancer. Twenty-six patients were taking immunosuppressive medication. Over 80% of women were symptomatic at the time of diagnosis. One half had a lesion involving the perineum and perianal region. The follow-up period was more than 5 years for 215 patients and more than 10 years for 102. Half of all patients required a second treatment for VIN by 13.7 years, but most recurrences were in the first 5 years. Recurrent disease was more likely in women over 30 years of age (92 of 256; 36%) than in women less than 30 years of age (30 of 126; 24%) (P = 0.014). Initial treatments were most often surgical excision (n = 196) or laser vaporization (n = 118), but 5-fluoruracil and imiquimod were also used. Similar percentages of patients treated by surgical excision or laser vaporization had a recurrence of disease within 5 years of initial treatment (34% and 39%, respectively). The risk of recurrence within 5 years estimated to be over 50% for patients with positive surgical margins and 15% for patients with negative margins. There were 63 women who received no treatment. The lesion regressed before treatment could begin in 47 patients and progressed to invasion before treatment in 10 patients. In addition, 5 very young patients are being followed with the expectation that the lesion will spontaneously regress, and one woman, who has a slowly increasing area of white plaque over the vulvar skin, has consistently refused treatment for over 20 years. Twenty-seven women, of whom 17 were treated with surgical excision or laser vaporization and 10 were “untreated” (received only diagnostic biopsy or partial excision), have developed squamous cell carcinoma of the vulva or perianal area more than 1 year from their diagnosis. Of the 17 women who developed invasive carcinoma of the vulva, perianus, or urethra, 10 had been treated for VIN more than once, including 3 with 4 or more previous treatments. Three had carcinoma develop in more than one area. Nine of the 17 women who developed invasive disease had positive histologic margins and were considered treatment failures. The median disease-free interval for these patients was 2.4 years (range, 1.1–7 years). The remaining 8 women who were subsequently diagnosed with invasive vulvar disease seemed to have new cancers arising in the “field” of the previous lesion. The median disease-free interval for these patients was 13.5 years (range, 3–16 years). Invasive cancer developed in 10 women with untreated VIN, 5 of which occurred in the early years of this study when no treatment was the policy. The remaining 5 were untreated because of comorbid conditions or physician or patient preference. Five women were considered to be strong candidates for spontaneous regression of disease. They were all under 25 years of age and had small, popular pigmented lesions. These patients are currently under observation with the expectation that these lesions will regress.