The incidence of human papillomavirus (HPV+)-associated head and neck squamous cell carcinoma (HNSCC) has increased dramatically over the past decades and continues to rise. HPV vaccination is not expected to affect this epidemic due to the long latency period from infection to tumor formation until 2060. Despite a higher cure rate, 20-30% of patients relapse and treatment options are limited.
To determine why some patients respond better to radiation therapy than others, researchers from the Department of Otolaryngology/Head and Neck Surgery at the University of North Carolina School of Medicine and Comprehensive Cancer Center. published a study showing that HPV+ head and neck cancer can be divided into two different subtypes that determine patient response to treatment, one of which is more sensitive to radiotherapy. They also discovered a new mechanism of carcinogenesis that underpins 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, difficulty swallowing, and hardening of the arteries, can last a lifetime. It can be difficult for doctors to determine the outcome due to the type and intensity of treatment without knowing how the patient’s tumor will respond to therapy.
To address this need, team members coordinated a research team at UNC, drawing on publicly available data from the University of Chicago and some validation data from E1308, a large national collaborative clinical trial.
They then analyzed tumor samples and identified several groups of co-expressed genes. Only one of these groups of co-expressed genes differentiated between high and low-expressing tumors, and analysis of the genes in this group showed that they were targets of a major transcription factor called NF-kB. NF-kB plays an important role in inflammation and cell death and is associated with HNSCC carcinogenesis.
Both subtypes were directly correlated with the evolution of 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 mutated in cancer. mutations, number of mutations, viral gene expression and integration, gene methylation, and infiltration of certain immune cells into the tumor.
Patient survival was the most obvious and important difference between the two types of tumors, and based on these, cell models of each subtype were built in the laboratory.
Tumors with increased NF-kB activity responded better to radiation therapy, which could help improve patient survival.
Ultimately, these data can be used to determine which therapies can be safely de-intensified to treat the tumor, reduce side effects, and improve quality of life.