Natural History and Management of Fanconi Anemia Patients With Head and Neck Cancer: A 10-Year Follow-up

To the Editor

Kutler et al. reviewed surgical outcomes in 35 patients with Fanconi anemia (FA) who developed head and neck cancer (HNSCC).¹ They found that surgery works well up front but late events are common. In our view, the experiences of these sentinel patients together with the literature shed light on critical research questions.

First, it is informative to compare 5- and 10-year HNSCC survival in FA versus general population patients followed through the Surveillance, Epidemiology, and End Result (SEER) Program.² The 5-year survival in the general population with HNSCC was 75% for human papilloma virus (HPV)-positive patients and 55% for HPV-negative patients;³ the latter resembles the 5-year survival of about 50% in the FA patients in the Kutler study. However, SEER data indicate that 10-year survival in the general population is about 50%, compared with about 25% in Kutler’s paper. This suggests that surgery is as effective in FA as in the general population in the short term, but complications from irradiation,4 and late effects such as recurrence or new malignancies, are more common in FA. Hence HNSCC in FA needs to be detected earlier.

Second, the etiology of HNSCC in FA remains unclear. Importantly, there is another publication regarding the role of HPV in FA in addition to the two cited by Kutler et al. The first study by Kutler et al found HPV in 15/18 FA HNSCC,⁵ while the second independent study found no HPV in 16 FA HNSCC.⁶ We also found no HPV in 5 FA HNSCC as well as no HPV in 4 HNSCC from dyskeratosis congenita patients.⁷ Hence, the most recent two studies did not find any HPV. In addition, most HNSCC in FA present in the oral cavity, but in general, HPV positive HNSCC are typically found in the oropharynx. ⁸ While we all agree that the HPV vaccine should be given to patients with FA, the vaccine will not prevent HNSCC in FA if HPV is not the cause. More studies are needed to identify the ways that HNSCC is initiated and promoted in FA.

Finally, since increasing numbers of persons with FA are expected to live long enough to develop HNSCC, larger cohorts of patients should be assembled, to inform individualized risk estimates (i.e., with and without stem cell transplant, etc.), as well as surveillance guidelines (i.e. what screening, and how often?).