2023-08-02 04:05:32
The incidence of head and neck squamous cell carcinoma (HNSCC) associated with human papillomavirus (HPV+) has increased dramatically in recent decades and continues to rise. Due to the long latency from infection to tumor formation, HPV vaccination is not expected to affect this epidemic until 2060. Despite the higher associated cure rate, 20-30% of patients suffer recurrences and curative options are limited.
To determine why some patients respond better to radiation therapy than others, researchers at the UNC School of Medicine’s Department of Otolaryngology/Head and Neck Surgery and the Lineberger Comprehensive Cancer Center formed a strong collaboration with researchers at the UNC Cancer Center. Yale, and have published a study, which reveals that HPV+ head and neck cancers can be divided into two different subtypes that determine the response of patients to treatment, one of them being more sensitive to radiotherapy. They also discovered a new mechanism of carcinogenesis that reinforces the growing efforts to personalize treatment.
Currently, many patients are treated with high doses of radiation combined with chemotherapy. But the side effects—including muscle fibrosis, swallowing difficulties, and hardening of the arteries—can last a lifetime. Determining the outcome can be difficult for doctors because of the type and intensity of treatment without knowing how the patient’s tumor will respond to the therapy.
To address this need, team members coordinated a research cohort at UNC, drawing on publicly available data from the University of Chicago, and some validation data from E1308, a large national cooperative group clinical trial.
They then analyzed the tumor samples and identified several groups of co-expressed genes. Only one of these groups of co-expressed genes separated high- and low-expressing tumors, and analysis of the genes in this group found that they represented targets of a master transcription factor called NF-kB. NF-kB plays an important role in inflammation and cell death and has been linked to the carcinogenesis of HNSCC.
Both subtypes were directly correlated with the evolution of the patients. Tumors with low NF-kB activity were associated with a worse prognosis, while tumors with high NF-kB activity were associated with a better prognosis, although they differ markedly from each other, from the genes that were mutated in the cancers. , factors driving mutations, number of mutations, virus gene expression and integration, gene methylation, and infiltration of certain immune cells into the tumor.
Patient survival was the most obvious, and important, distinction between the two types of tumors, and from these, cell models of each subtype were built in the laboratory.
Tumors with elevated NF-kB activity responded better to radiotherapy, which might help improve patient survival.
Ultimately, these data might be used to identify which therapy can be safely de-intensified to treat the tumor, decrease side effects, and improve quality of life.
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