New classification method for HPV-associated head and neck cancers

HNSCC cases linked to HPV+ increase significantly.


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Over the past few decades, the number of cases of head and neck squamous cell carcinoma (HNSCC) related to the human papillomavirus (HPV+) has risen significantly and is still rising. The human papillomavirus (HPV) has been linked to an increase in cancer of the throat and tonsils, which is projected to become the most common form of head and neck cancer by 2030. 

Identifying the right patients with HPV-related cancers is a major challenge in reducing treatment intensity. A new study identifies a subclass of HPV+ head and neck squamous cell carcinomas (HNSCC). It shows that treatment depends on the tumor type. The data show two distinct subtypes of HPV+ HNSCC, each with its features and treatment responses. 

The researchers examined data from 104 HPV+ HNSCC tumors and two publically available sources to find gene expression patterns that might reliably distinguish distinct tumor types. Among the 22 modules tested, one accurately classified HPV+ HNSCC tumors based on a different gene expression pattern. The NFKB classifier accurately predicted a favorable result in patients treated in the ECOG-ACRIN Cancer Research Group trial E1308, even with low-dosage radiation.

Barbara Burtness, a Professor of Medicine at Yale School of Medicine, said, “This discovery opens new opportunities for treatment personalization, as we can now better understand the distinct requirements for tumor development in each subclass.” 

The findings have significant clinical implications. Clinicians treating HPV+ HNSCC are constantly looking for biomarkers that can be used to determine treatment intensity. The new study shows that two prognostic subclasses with varying amounts of NF-B activity may be identified using various methods due to dramatic disparities in many characteristics of the cancer genomes. These groups are highly prognostic and contain prior findings concerning the predictive value of viral integration. 

The critical difference between HPV-associated head and neck cancers is the activation of the NF-B signaling pathway, which causes cellular growth, new blood vessel formation, and increased protection against cell death. Patients in this subgroup had better clinical outcomes and were more sensitive to radiation therapy. 

The researcher from Yale University said, “Currently, aggressive combination therapy is used to treat HPV+ HNSCC, but this new data shows that patient responses could vary significantly depending on the specific molecular features of their tumor. With the identification of distinct tumor subclasses, we may be able to tailor treatments to individual patients, potentially reducing their suffering from treatment while also helping with therapeutic decisions.”

The result shows that An unbiased technique was used to identify robust gene expression profiles in three HPV+ HNSCC cohorts, highlighting important biochemical pathways and cell types linked with each profile.

In conclusion, the information presented here shows two fundamentally distinct HPV-positive head and neck cancer subtypes. The fraction of HPV+ HNSCC that is NF-B active has a distinctive pattern of NF-B-related gene expression and significantly distinct mutational and methylation patterns.

The Yale Head and Neck SPORE program and the ECOG-ACRIN Cancer Research Group (ECOG-ACRIN) funded this study.

Journal Reference:

  1. Travis P. Schrank, Aditi Kothari, etal. Noncanonical HPV carcinogenesis drives radiosensitization of head and neck tumors. Proceedings of the National Academy of Sciences. DOI: 10.1073/pnas.2216532120 


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