BACKGROUND: Fanconi anemia (FA) is a rare autosomal recessive disorder 
characterized by a high degree of genomic instability and predisposition to 
cancer development. Recent evidence suggests that the incidence of head and neck 
squamous cell carcinoma (HNSCC) may be increased in patients with FA.
OBJECTIVE: To determine the cumulative incidence, tumor distribution, and 
outcome of HNSCC in patients with FA.
DESIGN AND SETTING: We analyzed data from 754 subjects from the International 
Fanconi Anemia Registry, a prospectively collected database of patients with FA.
MAIN OUTCOME MEASURES: Cumulative incidence of HNSCC and 2-year overall, 
relapse-free and disease-specific survival.
RESULTS: Of the 754 patients in the International Fanconi Anemia Registry, 19 
(3%) had HNSCC. This is a significantly higher incidence of HNSCC compared with 
that observed in the general population (standardized incidence ratio, 500; 95% 
confidence interval, 300-781) (P<.001). The patients' age ranged from 15 to 49 
years (median, 31 years), and there was a 2:1 female predominance. Surgical 
treatment was well tolerated (n = 17); however, radiation therapy and 
chemotherapy were associated with significant morbidity and mortality. Of the 19 
patients, 10 (53%) developed locoregional recurrences within a median of 16 
months from diagnosis. The median follow-up was 29 months. The 2-year 
disease-specific, overall, and relapse-free survival rates were 49%, 49%, and 
42%, respectively. The cumulative incidence of relapse by the age of 40 years 
was 50%.
CONCLUSIONS: In patients with FA, there is a high incidence of aggressive HNSCC 
at a young age. Surgery remains the mainstay of treatment because patients with 
FA tolerate radiation therapy and chemotherapy poorly, with significant 
morbidity. An increased understanding of FA-associated malignancies is not only 
important in the clinical management of patients with FA but can also elucidate 
the role of chromosomal instability in the development of HNSCC in general.