Topical treatment found noninferior to surgery for the treatment of vulvar high-grade squamous intraepithelial lesions
Surgery and laser vaporisation is the standard treatment for vulvar high-grade squamous intraepithelial lesions (vHSIL), but recurrences are observed in 50% of patients. Topical, non-surgical alternatives, which preserve vulvar anatomy, may be an effective alternative, but it has not been compared against surgery in a randomised trial until recently.
Trutnovsky et al. conducted a randomised clinical trial to compare the clinical effectiveness, histological response, HPV clearance, acceptance, and psychosexual morbidity of primary imiquimod treatment versus surgical treatment in women with vHSIL.
The authors found similar results across the two treatment groups, achieving noninferiority of imiquimod. For the primary outcomes, treatment with imiquimod resulted in a complete clinical response rate of 80% at 6 months, compared with 79% after one surgical intervention.
In this study, between 2013 and 2020, 146 women were assessed for eligibility across six hospitals in Austria. Patients between 18-90 years of age were eligible with histologically confirmed vHSIL with visible unifocal or multifocal lesions. Exclusion criteria included: women who had clinical suspicion of invasion; were immunocompromised; pregnant; lactating; had a history of vulvar cancer or severe inflammatory dermatosis of the vulva; known hypersensitivity to imiquimod, or undergoing active treatment for vHSIL.
In this trial, imiquimod was self-administered in a slowly escalating dosage scheme up to three times per week for up to 6 months. Patients were assessed with vulvoscopy, vulvar biopsy, HPV tests, and patient-reported outcomes at baseline and at 6 months and 12 months. Overall, clinical response to treatment was reported in 107 patients (54 in imiquimod and 53 in surgery). Nighty-eight patients (46 in the imiquimod and 52 in surgery) completed the study per protocol. 37 (80%) of 46 patients using imiquimod had a clinical complete response, compared with 41 (79%) of 52 patients after one surgical intervention, showing non-inferiority of the new treatment (difference in proportion –0·016, 95% CI –0·15 to –0·18; p=0·0056).
In the surgery group, 5 patients experienced invasive disease, compared to none in the imiquimod group after treatment. Progression to invasion during imiquimod treatment is a potential concern, so these results are positive.
There was no significant difference in HPV clearance, or adverse events. In the surgery group, local pain was more intense after surgical treatment, and local pruritus and erythema being more common in the imiquimod group. Psychosexual distress, sexual activity, and fear of progression showed no significant differences between study groups at 6 months and 12 months follow-up. No significant differences were found in treatment satisfaction between groups.
Limitations of the study included a relatively small sample size (due to the low incidence of vHSIL and therefore participants eligible for the trial), and strict exclusion criteria.
Overall, this was the first prospective trial of imiquimod versus surgery for the treatment of vHSIL. Findings from this study suggest that imiquimod may be as safe and effective as surgery in women with vHSIL and can be considered first-line treatment.
Study: Topical imiquimod versus surgery for vulvar intraepithelial neoplasia: a multicentre, randomised, phase 3, non-inferiority trial. G Trutnovsky G et al. The Lancet 399 (10337) 2022, 1790-1798, https://doi.org/10.1016/S0140-6736(22)00469-X.