Squamous Cell Carcinomas of the Head and Neck in Fanconi Anemia: Risk, Prevention, Therapy, and the Need for Guidelines

Abstract

Fanconi anemia (FA) is a rare recessive DNA repair disorder that is clinically characterized by congenital malformations, progressive bone marrow failure, and increased incidence of malignancies, especially acute myeloid leukemia and squamous cell carcinomas of the head and neck (HNSCCs) and the anogenital regions. On a cellular level, typical features of the disorder are a high degree of genomic instability and an increased sensitivity to bi-functionally alkylating agents. So far, germ-line defects in 15 different FA genes have been identified. Some of these FA genes are also established as tumor susceptibility genes for familiar cancers. In recent years, the prevention and therapy of HNSCCs in FA patients has become more important as the percentage of patients surviving into adulthood is rising. HNSCCs appear in very young FA patients without common risk factors. Since cisplatin-based chemotherapy in combination with radiotherapy, essential parts of the standard treatment approach for sporadic HNSCCs, cannot be used in FA patients due to therapy-associated toxicities and mortalities even with reduced dosing, surgery is the most important treatment option for HNSCCs, in FA patients and requires an early and efficient detection of malignant lesions. So far, no uniform treatment protocol for the management of HNSCCs in FA patients exists. Therefore, we propose that the information on affected FA patients should be collected world-wide, practical therapeutic guidelines developed and national treatment centers established.

Noninvasive Molecular Screening for Oral Precancer in Fanconi Anemia Patients

“…As life expectancy of patients with Fanconi anemia has increased markedly due to improved results of SCT, the number of patients developing HNSCC will increase consequently (23,24,45). A major problem of HNSCC in Fanconi anemia is that treatment possibilities are limited because patients with Fanconi anemia tolerate radiotherapy and chemotherapy poorly.…”

Epidemiologic Trends in Head and Neck Cancer and Aids in Diagnosis

“…HNSCC is the most common solid malignancy seen in patients with DC. The oral cavity is the predominant site for HNSCC in both FA and DC patients, frequently occurring in the tongue 18 . Hence, semiannual oral cancer screenings are recommended for both FA and DC patients beginning at a very young age.…”

Cancer stem cells are enriched in Fanconi anemia head and neck squamous cell carcinomas

“…HNSCC in FA patients carries a poor prognosis and requires early intervention and aggressive surgical treatment (3). Radiation and chemotherapy have limited value in treating HNSCC in FA patients because their normal cells are highly sensitive to DNA cross-linking agents (3).…”