Adjuvant prophylactic human papillomavirus (HPV) vaccination in patients treated for vulvar high-grade squamous intraepithelial lesions (vHSIL); a systematic review

Objective To evaluate the effectiveness of adjuvant human papillomavirus (HPV) vaccination in reducing recurrence of vulvar high-grade squamous intraepithelial lesion (vHSIL) following standard treatment, and to synthesize current evidence to guide clinical practice and future research. Methods A systematic search of Medline ALL, Embase, Web of Science, and Cochrane Central was conducted for studies published between 2002 and January 2025 and was updated in August 2025, supplemented by grey literature searching. Eligible studies reported vHSIL recurrence in women receiving adjuvant HPV vaccination after treatment with surgery, laser ablation, or imiquimod. Case reports, animal studies, and studies lacking vHSIL-specific recurrence data were excluded. Two reviewers independently screened studies, extracted data, and resolved discrepancies through discussion. Due to heterogeneity in study design, populations, and outcome definitions, a formal meta-analysis was not feasible; instead, effect estimates were qualitatively compared and presented in a forest plot. Results Of 419 records identified, two studies met inclusion criteria: One retrospective analysis of pooled randomized controlled trial data and one case-control study. Together, these studies included 740 women, of whom 251 received quadrivalent HPV vaccination. Recurrence occurred in 14.3% of vaccinated versus 15.9% of unvaccinated patients. Individual study estimates suggested a reduction in recurrence risk ranging from 40% to 63% in vaccinated women. A pooled odds ratio (OR) of 0.79 (95% CI: 0.45–1.39) indicated no statistically significant association between HPV vaccination and recurrence risk, with considerable imprecision due to the limited sample size and heterogeneity. Conclusion Current evidence does not demonstrate a statistically significant association between adjuvant HPV vaccination and vHSIL recurrence and remains limited and of low certainty. Larger, well-designed prospective trials are urgently needed to determine the true effectiveness of HPV vaccination as an adjuvant therapy in vHSIL management.