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Limited Data Available on Genetic Drivers of HNSCC in Low- Risk Patients

by ENTtoday •

Comment: In recent years, there has been a rise in the incidence of HNSCC—particularly of the oral cavity—in low risk, nontraditional patients. To date, studies have implicated mutations in DNA repair mechanisms and apoptosis pathways among other genes. Further understanding of the genetic factors that predispose low-risk patients to develop HNSCC is essential to improve treatment and clinical outcomes. —Andres Bur, MD

What is the current landscape of genetic determinants of HNSCC in low-risk patients?

Bottom line
At present, there is a lack of robust, comprehensive data on genetic drivers of oncogenesis in low-risk patients and a clear need for further research on genetic alterations underlying the rising incidence of HNSCC in low-risk, nontraditional patients.

Background: The past two decades have seen an increased incidence of head and neck squamous cell carcinoma (HNSCC) in a nontraditional, low-risk patient population (i.e., younger than 45 years of age with no history of substance use), owing to a combination of human papillomavirus (HPV) infection and individual genetic variation. Recently, the International Head and Neck Cancer Epidemiology (INHANCE) consortium aimed to compare the role of family history of HNSCC, tobacco, and alcohol as oncologic risk factors among a large cohort of young (≤45 years) and older (≥45 years) patients.

Importantly, a higher proportion of oral tongue and oral cavity cancers was seen in young patients with HNSCC. Compared with older patients, these cancers were found to be less attributable to tobacco and alcohol use and had a higher association with a family history of early onset HNSCC. As such, differences in HNSCC etiology among low-risk, nontraditional patients and their older counterparts are evident. The association of HNSCC with family history in the setting of a weaker (or absent) contribution from tobacco and alcohol suggests a hereditary, germline component present in young patients that is absent in the traditional HNSCC cohort.

Study design: Articles positing genetic variants as contributing factors in HNSCC incidence in low-risk, nontraditional patients were identified using a PubMed search, reviewed in detail, and concisely summarized.

Synopsis: Recent data suggest that common polymorphisms in DNA repair enzymes, cell-cycle control proteins, apoptotic pathway members, and Fanconi anemia-associated genes likely modulate susceptibility to HNSCC development in low-risk, nontraditional patients.

Citation: Gingerich MA, Smith JD, Michmerhuizen, NL, et al. Comprehensive review of genetic factors contributing to head and neck squamous cell carcinoma development in low-risk, nontraditional patients. Head Neck. 2018;40:943–954.