Strategies for early detection and detailed characterization of oral lesions and head and neck squamous cell carcinoma in Fanconi anemia patients

Fanconi Anemia (FA) is an inherited disorder associated with profound DNA repair defects, marked by failure to thrive, congenital malformations, progressive bone marrow failure (BMF), and an increased susceptibility to cancer. Clinical manifestations of FA vary widely, with BMF and clonal evolution predominantly affecting younger individuals, while adults are more frequently presenting with solid tumors. Individuals with FA are at a 500-fold increased risk of developing head and neck squamous cell carcinoma (HNSCC), which tends to appear at a median age of 30 years, often at advanced stages with only a 57 % two-year survival rate. The DNA repair deficiency prohibits the use of cisplatin and radiation therapy, limiting the treatment options for FA patients. Given the critical importance of early HNSCC detection in FA patients, innovative and less invasive diagnostic techniques are needed. This review discusses the role of brush biopsy-based cytology combined with molecular and morphometric analyses, as well as next-generation sequencing. Cytology alone demonstrated significant potential for detecting high-grade oral epithelial dysplasia and early-stage HNSCC, achieving sensitivities and specificities of 97.7 % and 84.5 %, respectively. Such techniques allow for stringent surveillance of the oral cavity in FA patients, essential given the aggressive nature of HNSCC in FA and the limited treatment options. In the absence of oral mucosal lesions, a six-month follow-up is recommended. For oral lesions persisting beyond three weeks, diagnostic evaluation is warranted, with clinical follow-up every three months for low-grade dysplasia and treatment of high-grade dysplasia. Integrating modern diagnostic tools within a comprehensive screening framework, alongside patient participation, is essential for personalized care, improved surveillance, and developing preventive measures to enhance FA patient care.