Background/Objectives: Vulvar squamous cell carcinoma (VSCC) is a rare gynecologic malig-nancy, with most cases arising from differentiated vulvar intraepithelial neoplasia (dVIN). Ap-proximately one-third of VSCC cases originate from high-grade squamous intraepithelial lesions (HSIL), which are associated with persistent infection by high-risk human papillomavirus (hrHPV) types. This study aimed to quantify circulating microRNAs (miRNAs) in the plasma of patients with premalignant conditions (dVIN and HSIL) and VSCC using TaqMan Low-Density Arrays. Methods: Plasma samples were collected from 40 patients, including those treated for HSIL, dVIN, and VSCC. Quantitative real-time PCR (qRT-PCR) identified circulating miRNAs differentially expressed in the plasma of VSCC patients compared to those with precancerous lesions. Results: A total of 31 differentially expressed miRNAs (DEMs) were found to be significantly upregulated in plasma from VSCC patients compared to precancerous cases. None of the analyzed miRNAs were able to distinguish VSCC cases based on hrHPV tumor status. Conclusions: This study provides strong evidence that a distinct set of miRNAs can differentiate between plasma samples from VSCC patients and those with precancerous lesions. Thus, these DEMs have potential diagnostic and prognostic value. "Predisposing" DEMs could be developed as biomarkers to aid in the as-sessment of vulvar lesions, helping to exclude or confirm progression toward cancer.

The authors have declared no competing interest.

This research was funded by the Polish National Science Centre, grant number 2013/23/N/NZ5/03284.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Institutional Review Ethics Committees of the Maria Sklodowska-Curie National Research Institute of Oncology Warsaw, Poland (No. 44/2002, 16/2015) and of the Holycross Cancer Center in Kielce, Poland (No. 15/2014).

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Data are available upon reasonable request from the corresponding author.