In this guest blog, Lynda Ware, Senior Fellow in General Practice for Cochrane UK, looks at a new Cochrane review on treatments for vulval intraepithelial neoplasia (VIN) and Susan Cooper, Consultant Dermatologist, gives an expert commentary on the evidence and its application to practice.
Vulval intraepithelial neoplasia (VIN) is a chronic pre-cancerous skin condition of the vulva, which has a peak incidence under the age of 50 but can occur at any age.
VIN can be classified into usual-type VIN (uVIN) and differentiated-type VIN (dVIN). Usual-type VIN is linked to high-risk Human Papilloma Virus (types 16, 18 and 31 are the most commonly associated) and precedes almost all squamous cell carcinomas in younger women, and differentiated-type VIN is associated with chronic skin conditions such as lichen sclerosus et atrophicus.
Treatment for uVIN may be by surgical excision or ablative techniques or by using medical treatments. This Cochrane review combines the protocols from two separate Cochrane reviews ‘Medical interventions for high-grade vulval intraepithelial neoplasia’ (Pepas 2015) and ‘Surgical interventions for high-grade vulval intraepithelial neoplasia’ (Kaushik 2014) to enable comparisons to be made between the various types of treatment.
What did the review find?
Six RCTs were found, involving 327 women, and five NRSs with 648 women. Five of the RCTs evaluated medical treatments (imiquimod, cidofovir, indole-3 carbinol) and the other six studies (one RCT and five NRSs) looked at surgical treatments or photodynamic therapy.
There is moderate to high quality evidence that topical treatment (imiquimod or cidofovir) may effectively treat about half of uVIN cases after a 16-week course but the evidence on whether this is sustained is limited. Smaller lesions are possibly more likely to respond. The relative risk of progression to vulval cancer is uncertain. Both imiquimod and cidofovir appear to be fairly well tolerated.
Low quality evidence from the best NRS indicates that there is little difference in the risk of recurrence between surgical excision and laser vaporisation.There is about a 50% chance of recurrence at one year with both interventions. Multifocal lesions are at greater risk of recurrence and progression.
There were no completed studies comparing medical with surgical treatment (one is ongoing).
An expert’s commentary on the Cochrane Review’s findings
Dr Susan Cooper, Consultant Dermatologist, Oxford University Hospitals Foundation Trust and Chair of the British Society for the Study of Vulval Disease writes:
This review is welcome because the management of usual type vulval intraepithelial neoplasia (uVIN) is complex and challenging. Nomenclature has been difficult with VIN, once graded from 1-3, and now reclassified into usual type VIN (HPV related) and differentiated VIN (non-HPV related). A further recent WHO/International Society for the Study of Vulval Disease (ISSVD 2015) classification now re-terms usual type VIN as high grade squamous epithelial lesion or HSIL. Although this makes the literature confusing at times, ultimately it will help to ensure that the correct patients are enrolled into future studies as previous classifications may have included patients who would no longer be considered to have VIN today.
What are the treatment options for Vulval intraepithelial neoplasia?
In the past, surgical excision was the only treatment considered and many women underwent repeated surgery, despite a recurrence rate of 50% at one year. The current British Association for Sexual Health and HIV national guidelines on the management of vulval conditions states that surgical excision is the treatment of choice for VIN but medical management can be considered. There weren’t any head to head medical versus surgical treatment studies included in this review but it is heartening that there appears to be one such study underway that may help to answer this question. Imiquimod is the chief medical treatment and backed by a number of studies outlined in the review. Topical cidofovir is mentioned but it isn’t possible to prescribe this currently so it isn’t a realistic therapeutic option.
The real challenge is management of women with multifocal disease and recurrent disease. Women who are immunosuppressed, usually due to HIV infection or after transplantation, are especially difficult to manage. In these women, disease may be so extensive or recurrent that surgical treatment can be disfiguring. Medical options are really useful. The studies in the review included very small numbers of immununosuppressed women so it wasn’t possible for the authors to make any specific recommendations about treatment in these cases.
A joint approach is often helpful
Women with VIN may be seen by dermatologists, genitourinary medicine doctors, gynaecologists and gynae-oncologists, all of whom may have different approaches. A joint approach is often helpful. In practice, most specialist (often joint dermatology and gynae-oncology) clinics tend to do a mix and match approach, some surgical excisions, medical treatments and possibly laser too. Dermatologists have a great deal of experience in using Imiquimod for skin cancer and their advice can be helpful.
In Oxford I run a joint clinic for VIN patients with my colleague, Mr Pubudu Pathiraja , a consultant gynae-oncologist. We tend to advise excision for small symptomatic VIN lesions and always when there is any suspicion of invasive disease. We often discuss medical treatment if VIN is around the clitoris where excision might result in unacceptable anatomical changes, in multifocal disease or where the patient has a preference to avoid surgery. Some of our patients undergo both surgical and medical treatments.
It can be lonely and frightening to have Vulval intraepithelial neoplasia…
As a patient it can be lonely and frightening to have VIN as there is often no access to support services. Unlike patients with vulval cancer, patients with VIN do not routinely see the specialist cancer nurses, and their treatments are not listed or discussed at multidisciplinary team cancer meetings, although they may undergo very similar treatments to those women with invasive cancer. Surgery can be mutilating and disfiguring and psychological distress is common. Imiquimod application to the vulva is very painful and support with treatment might be beneficial as many women abandon treatment because of side effects. There is no specific support group for patients with VIN.
This Cochrane review helps doctors who treat uVIN to consider a range of treatment options when choosing the appropriate treatment modality in partnership with their patient.
Susan Cooper and Lynda Ware have no conflict of interest in relation to this article.
Usual-type vulval intraepithelial neoplasia: new evidence on treatment options by Susan Cooper is licensed under a Creative Commons Attribution-NoDerivatives 4.0 International License.
Based on a work at http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD011837.pub2/full.
Images have been purchased from stock.com for Evidently Cochrane and may not be reproduced.
Surgical interventions for high-grade vulval intraepithelial neoplasia. Cochrane Database of Systematic Reviews 2014, Issue 3. Art. No.: CD007928. DOI: 10.1002/14651858.CD007928.pub3., , , , , .
Medical and surgical interventions for the treatment of usual-type vulval intraepithelial neoplasia. Cochrane Database of Systematic Reviews 2016, Issue 1. Art. No.: CD011837. DOI: 10.1002/14651858.CD011837.pub2., , , , , .
Medical interventions for high-grade vulval intraepithelial neoplasia. Cochrane Database of Systematic Reviews 2015, Issue 8. Art. No.: CD007924. DOI: 10.1002/14651858.CD007924.pub3., , , , .
Clinical Effectiveness Group, British Association for Sexual Health and HIV. 2014 UK national guideline on the management of vulval conditions. London: British Association for Sexual Health and HIV (BASHH); 2014. Available from:http://www.bashh.org/documents/UK%20national%20guideline%20for%20the%20management%20of%20vulval%20conditions%202014.pdf