5 years ago

Barriers to generating PDX models of HPV-related head and neck cancer

Kayla M. Harmeyer, Gregory S. Weinstein, Anil K. Rustgi, Kathleen T. Montone, Devraj Basu, Phyllis A. Gimotty, Hiroshi Nakagawa, Nicole D. Facompre, Varun Sahu
Objectives/Hypothesis Delineate factors impacting the creation and use of patient-derived xenografts (PDXs) of human papilloma virus-related (HPV+) head and neck squamous cell carcinomas (HNSCCs). Study Design Laboratory-based translational study. Methods Fifty-one surgically resected HNSCCs, including 31 HPV + cancers, were implanted into NOD/SCID/IL-2Rγ-/- (NSG) mice using standardized methodology. Clinical and pathologic factors were tested for association with engraftment. The gross, histologic, and molecular features of established HPV + PDXs were analyzed in comparison to their tumors of origin. Results Negative HPV status and perineural invasion (PNI) were independent, additive factors associated with increased PDX formation. Epstein-Barr virus–positive (EBV+) human large B-cell lymphomas grew from 32% of HPV + HNSCC cases that failed to engraft. Successfully established HPV + PDXs retained basaloid histology and often developed cystic growth patterns typical of HPV + nodal metastases. They also maintained elevated p16INK4A levels and expression of E6/E7 viral oncogene transcripts. Conclusion Reduced engraftment by HPV + tumors lacking PNI likely results in selection biases in HNSCC PDX models. Formation of EBV + lymphomas in NSG mice further reduces the generation of HPV + models and must be ruled out before long-term use of PDXs. Nevertheless, the retention of distinctive pathologic traits and viral oncogene expression by HPV + PDXs provides a viable in vivo platform for basic and translational studies as well as a resource for generating advanced in vitro models. Level of Evidence NA. Laryngoscope, 127:2777–2783, 2017

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/lary.26679

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