LAUSR

INTRODUCTION Vulvar squamous cell carcinoma (VSCC) is a rare malignancy with an increasing incidence, especially in young women. Surgical treatment of VSCC is associated with significant morbidity and high recurrence rates, which is related to the limited ability to distinguish (pre)malignant from healthy tissue. There is a need for new tools for specific real-time detection of occult tumor lesions and localization of cancer margins in patients with VSCC. Several tumor-specific imaging techniques are developed to recognize malignant tissue by targeting tumor markers. We present a systematic review to identify, evaluate, and summarize potential markers for tumor-specific imaging of VSCC. METHODS Relevant papers were identified by a systematic cross-database literature search developed with assistance of an experienced librarian. Data were extracted from eligible papers and reported based on the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. VSCC-specific tumor markers were valued based on a weighted scoring system, in which each biomarker was granted points based on ranked eligibility criteria: I) percentage expression, II) sample size, and III) in vivo application. RESULTS In total 627 papers were included of which 22 articles met the eligibility criteria. Twelve VSCC-specific tumor markers were identified and of these 7 biomarkers were considered most promising: EGFR, CD44v6, GLUT1, MRP1, MUC1, CXCR-4 and VEGF-A. DISCUSSION This overview identified 7 potential biomarkers that can be used in the development of VSCC-specific tracers for real-time and precise localization of tumor tissue before, during, and after treatment. These biomarkers were identified in a small number of samples, without discriminating for VSCC-specific hallmarks such as HPV-status. Before clinical development, experimental studies should first aim at validation of these biomarkers using immunohistochemistry and cell line-based examination, discriminating for HPV-status and the expression rate in lymph nodes and precursor lesions.