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Updated: May 10, 2026
RNAscope for In situ Detection of Transcriptionally Active Human Papillomavirus in Head and Neck Squamous Cell Carcinoma
Published on: March 11, 2014
High frequency of activating PIK3CA mutations in human papillomavirus-positive oropharyngeal cancer
Anthony C Nichols1, David A Palma, Winsion Chow
1Victoria Hospital, London Health Science Centre, Department of Otolaryngology–Head and Neck Surgery, Room B3-431A, 800 Commissioners Rd E, London, ON N6A 5W9, Canada. Anthony.Nichols@lhsc.on
Importance:
Large-scale whole-exome sequencing studies of head and neck squamous cell carcinoma (HNSCC) have established that the disease is dominated by frequent mutations in tumor suppressor genes with rare activating mutations in oncogenes that would be easily targetable with molecular agents. There was evidence in these reports, however, that activating mutations in phosphoinositide 3-kinase catalytic subunit p110α (PIK3CA) were common in patients with human papillomavirus (HPV)-positive tumors. We set out to test this prediction in oropharyngeal patient samples from our institution.
Objective:
To confirm whether activating mutations in PIK3CA are frequent in HPV-positive HNSCC because this mutated oncogene represents a potential therapeutic target.
Design, Setting, And Participants:
A retrospective search of the London Health Sciences Centre pathology database was performed to identify oropharyngeal cancer samples. DNA from pretreatment primary site biopsy samples from 87 patients were tested for high-risk HPV types 16 and 18 by real-time polymerase chain reaction.
Main Outcomes And Measures:
Samples were tested for activating mutations at the 3 mutational hot spots (codons 542, 545, and 1047) by polymerase chain reaction followed by Sanger sequencing using forward and reverse primers.
Results:
Only 4 of 41 HPV-negative tumors (10%) demonstrated PIK3CA hot spot mutations, including 3 at codon 1047 and 1 at codon 542. Of 46 HPV-positive tumors, 13 (28%) demonstrated activating PIK3CA mutations, including 7 at codon 542, 5 at codon 545, and 1 at codon 1047. The difference in PIK3CA mutation frequency was significantly different between HPV-positive and HPV-negative cancers (P = .03).
Conclusions And Relevance:
Although there has been a suggestion that activating PIK3CA mutations are common in HPV-positive HNSCC, to our knowledge, this is the first study to clearly identify this phenomenon. Targeting PIK3CA with molecular agents in HPV-positive patients may be a mechanism to improve cure rates and decrease treatment toxic effects in this rapidly growing cohort of patients.
Insights
Activating mutations in phosphoinositide 3-kinase catalytic subunit p110α (PIK3CA) are significantly more common in human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC). This finding supports PIK3CA as a potential therapeutic target for HPV-positive HNSCC patients.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Head and neck squamous cell carcinoma (HNSCC) is often characterized by mutations in tumor suppressor genes.
- Activating mutations in oncogenes are rare in HNSCC, limiting targeted therapy options.
- Previous studies suggested a higher prevalence of phosphoinositide 3-kinase catalytic subunit p110α (PIK3CA) mutations in human papillomavirus (HPV)-positive HNSCC.
Purpose of the Study:
- To investigate the frequency of activating PIK3CA mutations in HPV-positive oropharyngeal squamous cell carcinoma.
- To determine if PIK3CA mutations represent a potential therapeutic target in this patient cohort.
Main Methods:
- Retrospective analysis of 87 oropharyngeal cancer patient samples from London Health Sciences Centre.
- Detection of high-risk HPV types 16 and 18 using real-time polymerase chain reaction.
- Analysis of PIK3CA mutations at hot spot codons (542, 545, 1047) via polymerase chain reaction and Sanger sequencing.
Main Results:
- Activating PIK3CA mutations were identified in 28% (13 of 46) of HPV-positive tumors.
- In contrast, only 10% (4 of 41) of HPV-negative tumors harbored PIK3CA hot spot mutations.
- The difference in PIK3CA mutation frequency between HPV-positive and HPV-negative HNSCC was statistically significant (P = .03).
Conclusions:
- This study provides the first clear evidence that activating PIK3CA mutations are frequent in HPV-positive HNSCC.
- Targeting PIK3CA with molecular agents may improve treatment outcomes for patients with HPV-positive HNSCC.
- This approach could enhance cure rates and reduce treatment-related toxicity in this growing patient population.
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07:43Four-color Fluorescence Immunohistochemistry of T-cell Subpopulations in Archival Formalin-fixed, Paraffin-embedded Human Oropharyngeal Squamous Cell Carcinoma Samples
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