Treatment of Fanconi Anemia-Associated Head and Neck Cancer: Opportunities to Improve Outcomes

Clin Cancer Res. 2021 Oct 1;27(19):5168-5187. doi: 10.1158/1078-0432.CCR-21-1259.


Fanconi anemia, the most frequent genetic cause of bone marrow failure, is characterized by an extreme predilection toward multiple malignancies, including a greater than 500-fold incidence of head and neck squamous cell carcinoma (HNSCC) relative to the general population. Fanconi anemia-associated HNSCC and esophageal SCC (FA-HNSCC) often present at advanced stages with poor survival. Surgical resection remains the primary treatment for FA-HNSCC, and there is often great reluctance to administer systemic agents and/or radiotherapy to these patients given their susceptibility to DNA damage. The paucity of FA-HNSCC case reports limits evidence-based management, and such cases have not been analyzed collectively in detail. We present a systematic review of FA-HNSCC treatments reported from 1966 to 2020, defining a cohort of 119 patients with FA-HNSCC including 16 esophageal SCCs (131 total primary tumors), who were treated with surgery, radiotherapy, systemic therapy (including cytotoxic agents, EGFR inhibitors, or immune checkpoint inhibitors), or a combination of modalities. We summarize the clinical responses and regimen-associated toxicities by treatment modality. The collective evidence suggests that when possible, surgical resection with curative intent should remain the primary treatment modality for FA-HNSCC. Radiation can be administered with acceptable toxicity in the majority of cases, including patients who have undergone stem cell transplantation. Although there is little justification for cytotoxic chemotherapy, EGFR inhibitors and tyrosine kinase inhibitors may be both safe and effective. Immunotherapy may also be considered. Most oncologists have little personal experience with FA-HNSCC. This review is intended as a comprehensive resource for clinicians.

Publication types

  • Systematic Review
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Carcinoma, Squamous Cell* / genetics
  • Carcinoma, Squamous Cell* / therapy
  • Fanconi Anemia* / complications
  • Fanconi Anemia* / genetics
  • Fanconi Anemia* / therapy
  • Head and Neck Neoplasms* / etiology
  • Head and Neck Neoplasms* / therapy
  • Humans
  • Squamous Cell Carcinoma of Head and Neck / etiology
  • Squamous Cell Carcinoma of Head and Neck / therapy