The diagnosis of vulval intraepithelial neoplasia

The diagnosis of VIN has increased as a result of high awareness among clinicians and a greater tendency to biopsy vulval lesions.1 The precise degree of risk of its evolution into invasive carcinoma is not known, but data suggest 20-30 per cent of patients will develop invasive squamous cell carcinoma (SCC) of the vulva.2

The condition was categorised as VIN 1 (Figure 1), VIN ,2 and VIN 3 (Figure 2), according to the degree of abnormality. However, there is no evidence that what was termed VIN 1 was a cancer precursor requiring treatment, so the International Society for the Study of Vulvovaginal Diseases recommended that the term VIN should be applied to high-grade squamous lesions (formerly termed VIN 2 and 3), where it is necessary for treatment to be directed at preventing progression to cancer.

Classification and risk factors
The new classification system was developed in 2004.3 High-grade VIN (VIN 2 and 3) is classified into two main groups: undifferentiated (basaloid, warty or bowenoid) and differentiated (formerly simplex type). These two variants have a different natural biology, risk factors and malignant potential.

Undifferentiated VIN, also known as vulval carcinoma in situ, vulval atypia, bowenoid papulosis, Bowen's disease and erythroplasia of Queyrat, mainly affects women in their thirties and forties and is highly associated with HPV infection (especially types 16 and 18).4,5 Other risk factors include previous or current genital warts and immunosuppression.

Undifferentiated VIN may also be associated with CIN and vaginal or anal lesions,6 and overall has a lower incidence of progression to invasive cancer than differentiated VIN.7 Differentiated VIN mainly affects postmenopausal women and there is a weak association with HPV infection.7 This type is rarely seen in pure form and is most often found adjacent to invasive SCC. There is an association with vulval dystrophy, either lichen sclerosus (Figure 3) or squamous hyperplasia.8

There is a much higher risk of SCC in ifferentiated VIN compared to undifferentiated VIN.7 It is relatively rare to make a diagnosis of differentiated VIN in the absence of invasion, implying that this variant has a short natural history, with rapid development of invasion.7 One study demonstrated that 58 per cent of patients with differentiated VIN had previous or current invasive vulval SCC or developed it subsequently.9 A strong link between VIN and cigarette smoking has been established by many studies, and there is a higher risk of progression to invasion in smokers.10

Diagnosis and treatment
Patients may be asymptomatic or report itching or burning genitalia. VIN may be uni- or multifocal. Raised brown, red, pink, white, or grey lesions of the vulva may be present. Owing to the fact that 40-50 per cent of patients are asymptomatic, the standard of diagnosis remains visualisation and biopsy of all suspect vulval lesions.2 VIN may be diagnosed by various healthcare providers, including dermatologists, gynaecologists, GPs and colposcopists, as well as those providing care in STI clinics.11 Tests to diagnose VIN include colposcopy and biopsy with histology.

Surgical excision is currently the standard treatment for VIN. Other treatment modalities include imiquimod 5% cream, topical 5-fluorouracil and carbon dioxide laser ablation.7,12

Long-term follow-up of patients with VIN is required because late recurrence is not uncommon and progression to invasion may occur in some, despite optimal treatment.

Avoiding the risk factors is most important in the prevention of VIN and its progression to invasive cancer. In addition, thorough management of associated disorders and screening for VIN are necessary, especially in high-risk individuals.

The association between VIN and infection with HPV emphasises the importance of HPV vaccination. Recent studies suggest that wide implementation of vaccination could prevent about half of vulval carcinomas in younger women and about two-thirds of intraepithelial lesions in the lower genital tract.13

Dr Anton Alexandroff is a specialist registrar at the department of dermatology, Leicester Royal Infirmary, and Dr Ekaterina P. Burova is consultant dermatologist with an interest in genital dermatology, Bedford Hospital Trust. Competing interests: None declared 

References
1. Iversen T, Tretli S. Intraepithelial and invasive squamous cell neoplasia of the vulva: trends in incidence, recurrence, and survival rate in Norway. Obstet Gynecol 1998;91:969-72.
2. Stefanescu BI. Vulvar intraepithelial neoplasia. An issue of gynecologic interest. Rev Med Chir Soc Med Nat Iasi 2005;109:764-9.
3. Sideri M, Jones RW, Wilkinson EJ et al. Squamous vulvar intraepithelial neoplasia: 2004 modified terminology, ISSVD Vulvar Oncology Subcommittee. J Reprod Med 2005;50:807-10.
4. Wendling J, Saiag P, Berville-Levy S et al. Treatment of undifferent- iated vulvar intraepithelial neoplasia with 5% imiquimod cream: a prospective study of 12 cases. Arch Dermatol 2004;140:1220-4.
5. Van Beurden M, ten Kate FJ, Smits HL et al. Multifocal vulvar intraepithelial neoplasia grade III and multicentric lower genital tract neoplasia is associated with transcriptionally active human papillomavirus. Cancer 1995;75:2879-84.
6. Bornstein J, Kaufman RH, Adam E et al. Multicentric intraepithelial neoplasia involving the vulva. Clinical features and association with human papillomavirus and herpes simplex virus. Cancer 1988;62:1601-4.
7. Zawislak AA, Price JH, Dobbs SP et al. The management of vulval intraepithelial neoplasia in Northern Ireland. Int J Gynecol Cancer 2006;16:780-5.
8. Haefner HK, Tate JE, McLachlin CM et al. Vulvar intraepithelial neoplasia: age, morphological phenotype, papillomavirus DNA, and coexisting invasive carcinoma. Hum Pathol 1995;26:147-54.
9. Yang B, Hart WR. Vulvar intraepithelial neoplasia of the simplex (differentiated) type: a clinicopathologic study including analysis of HPV and p53 expression. Am J Surg Pathol 2000;24:429-41.
10. Daling JR, Sherman KJ, Hislop TG et al. Cigarette smoking and the risk of anogenital cancer. Am J Epidemiol 1992;135:180-9.
11. Preti M, Van Seters M, Sideri M et al. Squamous vulvar intraepithelial neoplasia. Clin Obstet Gynecol 2005;48:845-61.
12. Alouini S, Mathevet P. Imiquimod for vulvar intraepithelial neoplasia. N Engl J Med 2008;359:93-4; author reply 94-5.
13. Hampl M, Sarajuuri H, Wentzensen N et al. Effect of human papillomavirus vaccines on vulvar, vaginal, and anal intraepithelial lesions and vulvar cancer. Obstet Gynecol 2006;108:1361-8.

Originally published in the June 2009 edition of MIMS Oncology & Palliative Care.

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