Medical images routinely used in cancer treatment may contain far more biological information than previously thought. An international study involving Umeå University Visiting Professor Lucas Kenner has shown that PET/CT scans can capture the molecular activity of particularly aggressive head and neck tumors, opening new possibilities for more accurate diagnosis and treatment planning.
Most head and neck cancers are so-called squamous cell carcinomas that affect tissues of the mouth, throat, and larynx. HPV-negative tumors, that is, tumors that are not caused by the human papillomavirus HPV, tend to be more aggressive and difficult to treat. Reliable markers to predict how these cancers will progress and how they will respond to treatment are lacking. But new research suggests that medical images already in use could also help identify and monitor high-risk tumors.
“Image processing has traditionally been used to determine the location and size of tumors,” said Lucas Kenner, visiting professor at Umeå University and corresponding author. “Our results show that the images also contain information about the molecular behavior of the tumor – how aggressive it is.”
The malignancy of a tumor is usually determined by a biopsy, which is a small sample of tissue from the tumor that is examined under a microscope. However, biopsies are invasive and time-consuming, and only a small portion of the tumor can be taken, meaning the most invasive areas may be missed. In this study, the research team analyzed tumor samples along with clinical PET/CT images from HPV-negative head and neck cancer patients. They found that tumors caused by activation of the Hedgehog signaling pathway, a key regulator of cancer growth, showed distinct patterns on PET/CT scans. These tumors accumulate more tracers used for imaging, reflecting higher biological activity and poorer prognosis. To test whether imaging also reflected treatment effects, the researchers blocked the hedgehog pathway in a laboratory experiment. The tumor growth slowed and the PET/CT signal changed simultaneously, mirroring the pattern seen in patients in the clinic.
“This is particularly encouraging because it suggests the possibility of noninvasively monitoring the response of biological treatments,” Kenner says.
This study establishes a framework for linking tumor biology and radiological features by combining molecular multiomics and quantitative image analysis. Such approaches are expected to contribute to AI-based cancer diagnosis and more personalized treatment decisions.
“Prospective studies are needed before we can use this in the clinic,” Kenner said. “However, this study shows how integrating imaging and molecular data can advance precision oncology.”
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Reference magazines:
Stoiber, S., Pölöske, D., Spielvogel, CP, et al. (18F) FDG PET/CT multiomics identifies HPV-negative head and neck squamous cell carcinoma of hedgehog origin. molecular cancer. DOI: 10.1186/s12943-026-02607-8

