What are the treatment options for vulval leukoplakia?

Treatment of Vulval Leukoplakia

Topical corticosteroids are the first-line treatment for vulval leukoplakia (most commonly lichen sclerosus and squamous cell hyperplasia), with topical imiquimod or photodynamic therapy (ALA-PDT) serving as effective alternatives for refractory cases or when corticosteroid side effects are problematic. 1

Understanding Vulval Leukoplakia

Vulval leukoplakia is not a single histological diagnosis but encompasses several conditions, most commonly:

• Vulvar lichen sclerosus 1
• Squamous cell hyperplasia of the vulva 1

These conditions share similar etiology and clinical presentation but have different histopathological changes. Both significantly impair quality of life and carry malignancy risk. 1

First-Line Medical Treatment

Topical Corticosteroids

Begin with high-potency topical corticosteroids as initial therapy, as this remains the standard first-line approach despite potential side effects. 1 Not all patients respond to corticosteroid therapy, necessitating alternative options. 1

Second-Line Medical Treatments for Refractory Cases

Topical Imiquimod

For corticosteroid-refractory cases, topical imiquimod demonstrates remarkable efficacy, achieving complete response in 58% of patients at 5-6 months compared to 0% with placebo. 2

Treatment protocol:

• Apply topically for 16 weeks 2
• Complete response rates: 36/62 patients (58%) versus 0/42 with placebo 2
• Response sustained at one year in 38% of patients, particularly with smaller lesions 2

Important considerations:

• Adverse events are more common than placebo, with dose reductions needed more frequently 2
• Common side effects include headache and fatigue 2
• Smaller VIN lesions respond better than larger ones 2

Photodynamic Therapy with 5-Aminolevulinic Acid (ALA-PDT)

ALA-PDT represents a highly effective, minimally invasive alternative that is particularly valuable for extensive lesions or those in anatomically sensitive areas. 3, 4

Treatment protocol:

• Apply 20% ALA aqueous solution to lesion 3, 5
• Seal with plastic film for 3 hours 4
• Irradiate with red light at 635±15 nm wavelength 4
• Power density: 60-90 mW/cm² 4
• Duration: 20 minutes per session 4
• Repeat every 2 weeks for 3 cycles 4
• Additional courses at 60 days if necessary 5

Clinical outcomes:

• Complete symptom resolution (pruritus) in 90% (27/30 patients) 4
• Pathological improvement in all treated subjects 4
• High patient satisfaction ("satisfied" or "very satisfied" in all cases) 4
• Minimal side effects: temporary pain, erythema, and swelling 4
• No disfigurement or systemic side effects 3

Topical Cidofovir

Cidofovir achieves similar complete response rates to imiquimod (46% versus 45% at 6 months), with slightly fewer side effects. 2 This represents a reasonable alternative when imiquimod is not tolerated. 2

Topical Retinoids (13-cis-retinoic acid)

For advanced dystrophies previously considered for vulvectomy, topical 13-cis-retinoic acid may avoid surgery:

• Complete disappearance in 50% (8/16 patients) 6
• Considerable regression in additional 44% (7/16 patients) 6
• Response typically occurs after 1-2 months of daily treatment 6
• Maintenance therapy for 2-4 months prevents recurrence 6
• Particularly effective in 2/3 patients with post-vulvectomy recurrence 6

Alternative Treatment Options

Other approaches include topical calcineurin inhibitors, systemic retinoids, various destructive techniques (laser vaporization, electrocauterization, cryosurgery), and platelet-rich plasma therapy, though evidence for these is more limited. 1

Surgical Treatment Considerations

Avoid surgical excision as primary treatment despite malignancy potential, as recurrence rates are extremely high (approximately 50% at one year) regardless of whether excision or laser vaporization is used. 2 Multifocal lesions have even higher recurrence rates (66% versus 34% for unifocal). 2

Reserve surgery exclusively for:

• Cases where occult invasive cancer is suspected despite biopsy showing only leukoplakia 2
• Failure of all medical therapies 1

Critical Pitfalls to Avoid

• Never perform primary surgical excision or vulvectomy unless invasive cancer is suspected—recurrence rates approach 50% and surgery does not prevent malignancy better than medical management 1, 2
• Do not abandon treatment after initial corticosteroid failure—multiple effective alternatives exist 1
• Recognize that multifocal lesions require more aggressive monitoring as they carry higher recurrence and progression risk 2
• Do not use destructive techniques (cryosurgery, electrocauterization) as first-line therapy due to postoperative pain, edema, and scarring 3
• Evidence for treatment effectiveness in immunosuppressed women is scant—these patients require closer monitoring 2

Monitoring for Malignant Transformation

While vulval cancer occurred in 15.1% of patients at median 71.5 months in surgical series 2, the relative risk of progression with medical versus surgical treatment remains uncertain. 2 Regardless of treatment modality chosen, long-term surveillance is mandatory given the malignant potential of these conditions. 1