Genetic Mutations in Young Nonsmoking Patients With Oral Cavity Cancer: A Systematic Review

Abstract

Objective This investigation aims to review the known genetic mutations associated with oral cavity squamous cell carcinoma (OCSCC) in young adults with limited environmental risk factors (YLERs). Data Sources A comprehensive search strategy was designed to identify studies in MEDLINE (Ovid), Embase (Ovid), and Scopus from database inception to May 2017 that included adults ≤50 years of age with OCSCC and minimal tobacco use history (≤10 pack-years) who had their tumors genetically sequenced or mutational profiles analyzed. Review Methods Identified articles were screened by 2 reviewers. Quality of evidence was graded by the MINORS criteria for case-control studies; other studies were graded by assigning a level of evidence for gene mutation literature. Results Thirteen studies met our inclusion criteria, and 130 patients met our criteria for age and tobacco history. TP53 was the most commonly evaluated gene (10 of 13 studies) and the most frequently observed mutation. One study reported that nonsmokers had significantly fewer TP53 mutations, while 9 studies found no difference in the prevalence of TP53 mutations. No other mutations were found specific to this cohort. Conclusions TP53 mutations may occur at a similar rate in YLERs with OCSCC as compared with older patients or those with risk factors. However, few studies have aimed to characterize the genetic landscape of oral cavity tumors in this population, often with small sample sizes. Future studies are needed to explore unidentified genetic alterations leading to tumor susceptibility or alternative mechanisms of carcinogenesis.

High Failure Rates in Young Nonsmoker Nondrinkers With Squamous Cell Carcinoma of the Oral Tongue

“…Although younger patients with squamous cell carcinomas of the oral tongue frequently lack significant exposure to traditional risk factors like alcohol or tobacco, their tumors may be genomically similar to those found in older patients with a smoking history. 11,34,[49][50][51][52] Other factors may be at play in explaining the apparent poor prognosis seen in some younger patients with SCCOT. For example, these malignancies may be less frequently recognized in younger patients by clinicians, patients, or both, leading to delayed presentations and worse outcomes.…”

“…Although younger patients with squamous cell carcinomas of the oral tongue frequently lack significant exposure to traditional risk factors like alcohol or tobacco, their tumors may be genomically similar to those found in older patients with a smoking history 11,34,49–52 . Other factors may be at play in explaining the apparent poor prognosis seen in some younger patients with SCCOT.…”

Contrasting clinical outcomes and socio‐economic impact of young versus elderly‐onset oral squamous cell carcinoma, a novel health economic analysis

“…Multiple theories have been proposed to explain this, such as a lower Ki-67 proliferation index, p53 and p63 expression in non-smokers. 5,30 Of interest, our cohort had a high proportion of non-smokers, comprising almost 60% of patients, mostly from Kerala and Singapore. This is unlike what we see in most studies evaluating OSCC and brings a new dimension to the available literature.…”

Characteristics of oral squamous cell carcinoma focusing on cases unaffected by smoking and drinking: A multicenter retrospective study

“…However, several recent studies have shown no difference in prognosis between the two groups 14,16 . Additionally, it has been reported that tongue cancers in young non‐smokers with no known risk factors for cancer and those in older people with a smoking history are genomically similar 4041 . Furthermore, it has recently been reported that for young patients with tongue cancer, local metastasis, higher tumor grade, and larger tumor size are associated with an increased risk of death in early‐ and late‐stage disease; however, in late‐stage disease, African American race, positive surgical margins, and distant metastasis are associated with poor prognosis 25 .…”