Preti Mario, Gallio Niccolò, Bornstein Jacob, Joura Elmar, Saçıntı Koray Görkem, Baptista Pedro Vieira
Department of Surgical Sciences, University of Torino, Torino, Italy.
Galilee Medical Center and Bar-Ilan University The Azrieli Faculty of Medicine, Bar-Ilan, Israel.
J Turk Ger Gynecol Assoc. 2025 Sep 3;26(3):230-234. doi: 10.4274/jtgga.galenos.2025.2025-7-5. Epub 2025 Jul 29.
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.
外阴上皮内瘤变（VIN）是一组异质性的癌前病变，通过不同的人乳头瘤病毒（HPV）相关和HPV非依赖途径产生。尽管在病因、预后和进展风险方面存在明确的差异，但目前的管理方法基本一致，主要是手术治疗。这种一刀切的方法忽视了个体化护理的机会，使患者，尤其是年轻女性和患有多灶性疾病的患者面临潜在可避免的性心理疾病。分子病理学的最新进展，包括免疫组织化学、基因组分析、DNA甲基化分析和拷贝数改变检测，为提高诊断准确性和进行风险分层提供了有前景的途径。将p16INK4a、p53等标志物以及新兴的甲基化检测组合纳入诊断流程，可能会改善病变亚型之间的区分，指导监测，并确定适合保守治疗的患者。此外，外阴高级别鳞状上皮内瘤变的独特发病机制与其他HPV相关癌症中由鳞柱交界（SCJ）驱动的模式不同，这凸显了对非SCJ上皮中宿主-病毒相互作用和早期致癌事件进行重点研究的必要性。未来的方向包括非侵入性采样方法、分子引导的监测方案、治疗性HPV疫苗以及联合免疫调节治疗，以减轻切除治疗的负担。建立基于精准医学的VIN治疗方法不仅可以保留外阴的完整性和功能，还可以通过针对性的预防和早期干预策略改善肿瘤治疗效果。
