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Comparative molecular profiling of HPV-induced squamous cell carcinomas
Robert F Koncar1, Rebecca Feldman2, El Mustapha Bahassi1
1Department of Internal Medicine, Division of Hematology/Oncology, University of Cincinnati, Cincinnati, Ohio.
Cancer Medicine
|May 31, 2017
Summary
Human papillomavirus (HPV) positive cancers of the anogenital region and oropharynx share similar molecular profiles. This suggests that common treatment strategies may be effective across these HPV-driven tumors.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Human papillomavirus (HPV) causes approximately 5% of all cancer incidences, primarily affecting the anogenital region and oropharynx.
- The molecular similarities across different HPV-mediated cancers remain largely unknown.
- Identifying common targetable alterations in HPV-positive tumors is crucial for developing effective therapies.
Purpose of the Study:
- To investigate whether distinct HPV-mediated cancers share a common molecular signature.
- To identify potential targetable genetic alterations across different HPV-positive tumor types.
Main Methods:
- Multiplatform molecular profiling of 743 p53 wild-type squamous cell carcinomas (anal, cervical, oropharyngeal, vulvar).
- Analysis included immunohistochemistry for 24 proteins, next-generation and Sanger sequencing for 48 genes, and in situ hybridization for six genes.
- Comparative analysis of mutation frequency, copy number alterations, and protein expression across cohorts.
Main Results:
- Remarkably similar molecular profiles were observed across all four HPV-positive cancer types.
- No statistically significant differences in gene mutation frequency or copy number alterations were found.
- Loss of ERCC1 and SPARC expression were the only significant differences identified via immunohistochemistry.
Conclusions:
- HPV-positive anal, cervical, oropharyngeal, and vulvar cancers exhibit highly similar molecular characteristics.
- Commonly mutated PIK3CA and concurrent loss of PTEN expression were noted.
- Loss of MGMT and RRM1 suggests potential predictive value for cytotoxic therapies, warranting further investigation.
