# Evaluating the effectiveness of various treatment modalities in vulvar high-grade squamous intraepithelial lesions (vHSIL): a systematic review

**Authors:** Vera J.G.M. Vaessen, Katerina Sidera, Ralf L.O. van de Laar, Heleen J. van Beekhuizen

PMC · DOI: 10.1016/j.gore.2026.102038 · 2026-02-13

## TL;DR

This systematic review compares the effectiveness of excision, laser ablation, and imiquimod for treating vulvar high-grade squamous intraepithelial lesions, highlighting the need for personalized treatment and better long-term data.

## Contribution

A systematic review of treatment outcomes for vHSIL, emphasizing the lack of a superior modality and the need for individualized strategies.

## Key findings

- Pooled complete response rates varied widely across excision, CO2 laser, and imiquimod treatments.
- Imiquimod had the lowest recurrence in HPV-negative patients but caused local adverse effects.
- High recurrence rates were observed across all treatment modalities, stressing the need for improved strategies.

## Abstract

•Systematic review comparing treatments for vulvar intraepithelial neoplasia.•Evaluates excision, laser ablation, and topical imiquimod therapy.•Synthesizes global evidence to guide individualized treatment strategies.•Highlights need for standardized follow-up and long-term outcome reporting.•Identifies gaps for future research in vulvar precancer management.

Systematic review comparing treatments for vulvar intraepithelial neoplasia.

Evaluates excision, laser ablation, and topical imiquimod therapy.

Synthesizes global evidence to guide individualized treatment strategies.

Highlights need for standardized follow-up and long-term outcome reporting.

Identifies gaps for future research in vulvar precancer management.

Vulvar high-grade squamous intraepithelial lesion (vHSIL) is a premalignant condition caused by persistent infection with high-risk human papillomavirus (HPV), with approximately 10% of cases progressing to vulvar carcinoma within ten years. This systematic review evaluates the effectiveness of surgical excision, CO2 laser ablation, and imiquimod cream in terms of complete response (CR) and recurrence rates.

A systematic review was performed following PRISMA guidelines, with literature searches conducted in Medline, Embase, and Web of Science (PROSPERO: CRD42024578702). Eligible studies included adult women (≥18 years) with histopathologically confirmed vHSIL requiring treatment. Two independent reviewers performed study selection and data extraction, and risk of bias was assessed using the Cochrane tools. Due to substantial study heterogeneity, a formal meta-analysis was not performed. Instead, pooled CR and recurrence rates were calculated using weighted averages, with 95% confidence intervals. Statistical heterogeneity was assessed with the I2 statistic and Chi2 test.

26 studies involving 1,705 patients were included. Pooled CR rates ranged from 55 to 100% for excision, 44–85% for CO2 laser, and 25–81% for imiquimod. Recurrence rates varied from 0 to 83%, with the lowest recurrence observed in HPV-negative patients treated with imiquimod. Excision resulted in rapid CR but had high recurrence rates, particularly with positive surgical margins. Imiquimod caused local adverse effects (burning, erythema, irritation), but preserved anatomy, as did CO2 laser ablation, which lacked histological control.

No single treatment modality proved superior, with all showing high recurrence rates. These results emphasize the importance of individualized treatment strategies and further research to reduce recurrence.

## Linked entities

- **Chemicals:** imiquimod (PubChem CID 57469)
- **Diseases:** vulvar carcinoma (MONDO:0005215)

## Full-text entities

- **Diseases:** vulvar (MESH:D014845), irritation (MESH:D001523), infection (MESH:D007239), postoperative pain (MESH:D010149), carcinoma (MESH:D009369), VIN (MESH:D002578), inflammatory (MESH:D007249), precancerous lesion (MESH:D011230), -grade squamous intraepithelial lesion (MESH:D000081483), psychosexual distress (MESH:D012128), erythema (MESH:D004890), squamous cell carcinoma (MESH:D002294), vulvar cancer (MESH:D014846)
- **Chemicals:** cidofovir (MESH:D000077404), lmiquimod (-), Imiquimod (MESH:D000077271), CO2 (MESH:D002245)
- **Species:** Human papillomavirus (species) [taxon 10566], Homo sapiens (human, species) [taxon 9606], Papillomaviridae (family) [taxon 151340]

## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12925432/full.md

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Source: https://tomesphere.com/paper/PMC12925432