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Feasibility of Targeting PIK3CA Mutations in Head and Neck Squamous Cell Carcinoma

  • Original Article
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Pathology & Oncology Research

Abstract

PIK3CA is the only frequently-mutated, directly druggable oncogene in head and neck squamous cell carcinoma (HNSCC). However, it is unclear if a molecularly-driven intervention trial can be launched successfully, particularly within a single-institution setting secondary to the infrastructure necessary for mutation detection, mutation prevalence, and patient willingness to participate. This study aimed to evaluate 1) local frequency of PIK3CA activating mutations in HNSCC, 2) timeliness of our mutation-profiling clinical pathway, and 3) patients’ willingness to enroll in a novel neoadjuvant drug trial. Tissue biopsies of 25 consecutive cases of HNSCC were tested for activating PIK3CA mutations at three mutational hotspots by real-time polymerase chain reaction. Mutations prevalence and number of working days accrued in determining PIK3CA mutational status were calculated. In addition, 30 HNSCC patients were surveyed prospectively regarding their willingness to participate in a hypothetical drug trial. Survey data were summarized descriptively. 4 of 25 (16 %) tumors harbored a PIK3CA activating mutation, including one at codon E542K, two at codon E545K/D, and one at codon H1047R. On average, this result was obtained in approximately 15 working days (range, 9–24 working days). The majority of patients surveyed (70 %) indicated their willingness to participate in a targeted PIK3CA trial. This study provides evidence that within a single institution, PIK3CA activating mutations can be detected with expected frequency, with sufficient timeliness and sufficient patient interest to mount a targeted intervention trial that may lead to improved tumor response in selected HNSCC patients.

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Acknowledgments

ᅟ

Author contributions:

Drs. Theurer and Nichols had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Compliance with Ethical Standards

ᅟ

Conflict of Interest

Dr. Nichols holds an investigator initiated grant from Novartis to study a PI3K inhibitor.

Funding

London Regional Cancer Program Catalyst Grant (ACN).

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committees and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed Consent

Informed consent was obtained from all individual participants included in the study.

Author information

Authors and Affiliations

  1. Department of Otolaryngology – Head and Neck Surgery, Schulich School of Medicine & Dentistry, Western University, 800 Commissioners Rd. E., London, ON, N6A 5W9, Canada

    Julie A. Theurer, John Yoo, Morgan Black, Nicole Pinto, John W. Barrett, S. Danielle MacNeil, Kevin Fung & Anthony C. Nichols

  2. School of Communication Sciences and Disorders, Faculty of Health Sciences, Western University, Elborn College, London, ON, N6G 1H1, Canada

    Julie A. Theurer

  3. Lawson Health Research Institute, 750 Base Line Rd., London, ON, N6C 2R5, Canada

    Julie A. Theurer, David Palma, John W. Barrett & Anthony C. Nichols

  4. Department of Pathology and Laboratory Medicine, Schulich School of Medicine & Dentistry, Western University, Dental Sciences Building, London, ON, N6A 5C1, Canada

    William Stecho, Keith Kwan, Bret Wehrli, Vimla Harry & Christopher J. Howlett

  5. Department of Oncology, Western University, 790 Commissioners Rd. E., London, ON, N6A 5W9, Canada

    John Yoo, Eric Winquist, David Palma, Suzanne Richter, John W. Barrett, S. Danielle MacNeil, Kevin Fung & Anthony C. Nichols

  6. London Health Sciences Centre, 800 Commissioners Rd. E., London, ON, N6A 5W9, Canada

    John Yoo, Keith Kwan, Bret Wehrli, Eric Winquist, David Palma, Suzanne Richter, John W. Barrett, S. Danielle MacNeil, Kevin Fung & Anthony C. Nichols

  7. Department of Otolaryngology – Head and Neck Surgery, London Health Sciences Centre – Victoria Hospital, Rm B3-451, 800 Commissioners Rd E., London, ON, N6A 5W9, Canada

    Julie A. Theurer

Authors
  1. Julie A. Theurer
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  2. William Stecho
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  3. John Yoo
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  4. Keith Kwan
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  5. Bret Wehrli
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  6. Vimla Harry
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  7. Morgan Black
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  8. Nicole Pinto
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  9. Eric Winquist
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  10. David Palma
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  11. Suzanne Richter
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  12. John W. Barrett
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  13. S. Danielle MacNeil
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  14. Kevin Fung
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  15. Christopher J. Howlett
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  16. Anthony C. Nichols
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Corresponding author

Correspondence to Julie A. Theurer.

Additional information

Drs. Howlett and Nichols contributed equally to this manuscript.

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Theurer, J.A., Stecho, W., Yoo, J. et al. Feasibility of Targeting PIK3CA Mutations in Head and Neck Squamous Cell Carcinoma. Pathol. Oncol. Res. 22, 35–40 (2016). https://doi.org/10.1007/s12253-015-9970-3

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  • DOI: https://doi.org/10.1007/s12253-015-9970-3

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