Review
Is the assumed natural history of vulvar intraepithelial neoplasia III based on enough evidence? A systematic review of 3322 published patients

https://doi.org/10.1016/j.ygyno.2005.02.012Get rights and content

Abstract

Objective

To establish the true natural history of VIN III from literature data.

Methods

In a systematic review, data of women with VIN III indexed in several computer databases were pooled. The effect of treatment was correlated with recurrences and progression of VIN III.

Results

Ninety-seven articles met the inclusion criteria. Data of 3322 patients were available. The mean age at diagnosis of VIN III was 46. This decreased over time, although not significantly (P = 0.08). Recurrences were seen as often after local excision as after vulvectomy. The percentage of recurrences was lower, but not absent, after free surgical margins than after involved surgical margins (P < 0.001). 6.5% of the 3322 patients progressed to an invasive vulvar carcinoma. Occult carcinomas were diagnosed in 3.2% of patients and 3.3% carcinomas were diagnosed during follow-up. The mean age at diagnosis of invasive vulvar carcinoma was 52 years. Nine percent of 88 untreated patients progressed in 12 to 96 months to invasive vulvar carcinoma. Only 1.2% of the 3322 patients showed complete regression, mostly during the first 10 months after diagnosis, 41% of which was related to pregnancy.

Conclusion

Evidence exists that VIN III may progress to invasive vulvar carcinoma. However, the available literature suggests that the progression rate to invasive vulvar carcinoma is low. The incidence of invasion as found in this systematic review is probably even too high, because overreporting of (micro)invasive cases cannot be excluded. Only a prospective registration using a standardized pathology examination will provide information about the real natural history of VIN III.

Introduction

The natural history of untreated VIN III is unclear. Untreated patients who hardly ever progress to an invasive vulvar carcinoma have been published [1], [2], [3]. Others have seen progression in nearly all untreated patients [4]. Since data on the follow-up of untreated VIN III are scarce, the natural history of VIN III is mainly based on the follow-up after surgical treatment of VIN III and is considered low [2]. Although extensive surgery, such as vulvectomy, is not the advised standard treatment anymore, removal of all visible lesions to exclude the presence of an occult invasive squamous cell carcinoma is still recommended [5].

The aim of this study was, by means of a systematic review, to assess both the risk of progression of VIN III in untreated patients and the effect of surgical treatment in relation to recurrences and progression of VIN III.

Section snippets

Data identification and extraction

Articles were located in November 2004 using various strategies. Firstly, computer searches of MEDLINE (from 1964), CANCERLIT (from 1980), EMBASE (from 1974), BIOSIS PREVIEWS AB (from 1970) and SCIENCE CITATION INDEX (from 1970) were performed. The following key words were used: vulvar neoplasms in combination with intraepithelial neoplasia, Bowen, bowenoid, Queyrat, carcinoma simplex, early vulvar cancer, hyperplastic dystrophy, condylomatous dysplasia, intraepithelial carcinoma, carcinoma in

Results

A total of 97 articles [1], [2], [3], [4], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38], [39], [40], [41], [42], [43], [44], [45], [46], [47], [48], [49], [50], [51], [52], [53], [54], [55], [56], [57], [58], [59], [60], [61], [62], [63], [64], [65], [66], [67], [68], [69], [70], [71], [72], [73], [74], [75], [76], [77], [78], [79], [80], [81], [82], [83],

Discussion

The dropping age (Fig. 1) coincides with the increased incidence of VIN III between 1975 and 1981 [101]. However, one must realize that both these findings could be due to an increased awareness of this disease.

In this systematic review, the mean age at diagnosis of the invasive vulvar carcinoma was 52 years, while the mean age at diagnosis of VIN III was 46 years. The young age of the patients with invasive vulvar cancer in this study gives support to the idea that there are two different

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