The future of research on vulvar intraepithelial neoplasia: towards precision diagnostics and risk stratification

Vulvar intraepithelial neoplasia (VIN) represents a heterogeneous group of premalignant lesions arising through distinct human papillomavirus (HPV)-associated and HPV-independent pathways. Despite well-characterized differences in etiology, prognosis, and progression risk, current management remains largely uniform and predominantly surgical. This one-size-fits-all approach neglects opportunities for individualized care and exposes patients, particularly younger women and those with multifocal disease, to potentially avoidable psychosexual morbidity. Recent advances in molecular pathology, including immunohistochemistry, genomic profiling, DNA methylation analysis, and copy number alteration detection, offer promising avenues for refining diagnostic precision and enabling risk stratification. Integration of markers such as p16INK4a, p53, and emerging methylation panels into diagnostic workflows may improve differentiation between lesion subtypes, guide surveillance, and identify candidates for conservative therapy. Moreover, the unique pathogenesis of vulvar high-grade squamous intraepithelial neoplasia, which diverges from squamocolumnar junction (SCJ)-driven models seen in other HPV-associated cancers, highlights the need for focused research on host-virus interactions and early oncogenic events in non-SCJ epithelium. Future directions include non-invasive sampling methods, molecularly-guided surveillance protocols, therapeutic HPV vaccines, and combined immunomodulatory treatments to reduce the burden of excisional therapy. Establishing precision-based approaches for VIN could not only preserve vulvar integrity and function but also improve oncological outcomes through targeted prevention and early intervention strategies.