Young non-smokers with oral cancer: What are we missing and why?

There has been an increase in young non-smokers (YNS) who develop oral cavity squamous cell carcinomas (OSCC). Oncological outcomes in YNS are controversial and etiology has not been well-defined. We hypothesize that the etiology of cancer development in YNS and their poor outcome is related to an impaired immune system.

From a database of 2073 OSCC patients treated with primary surgery between 1985 and 2015, 9% were young patients. We categorized patients as: ≤40 years-old/non-smokers (n = 100), ≤40 years-old/smokers (n = 80), >40 years-old/non-smokers (n = 595) and >40 years-old/smokers (n = 1298). Patient and tumor variables were used to calculate propensity scores and stabilized inverse probability of treatment weights were calculated. Weighted proportional hazard models were performed. Survival and recurrence outcomes of YNS were compared to the other 3 groups. Host immune status of YNS measured by peripheral blood neutrophil-to-lymphocyte ratio (NLR) was compared to 2 control groups (YNS with thyroid cancer and YNS with benign pathologies).

After adjusting for tumor and host factors, YNS had a higher probability of death compared to young smokers. This was driven by a higher incidence of regional and distant recurrences. Host factors showed a strong association with outcomes suggesting YNS may have an impaired immune system. Compared to the control cohorts YNS with OSCC had a higher NLR (p = .006).

When adjusted by relevant covariates, YNS with OSCC have poorer survival than their young smoker counterparts. Our results suggest that an impaired immune system may be partly responsible for OSCC development and poorer outcomes in YNS.