Rising incidence of oral tongue squamous cell carcinoma in young women: Emerging non-traditional etiologic factors and clinical implications: A structured narrative review

Oral squamous cell carcinoma (OSCC) accounts for the majority of oral malignancies worldwide, with oral tongue squamous cell carcinoma (OTSCC) considered one of its most aggressive subtypes. Historically, OSCC has predominantly affected older males with substantial tobacco and alcohol exposure. However, emerging epidemiologic evidence demonstrates a rising incidence of OTSCC among young females, particularly patients aged ≤ 45 years, many of whom lack these traditional risk factors, suggesting distinct etiologic pathways. A structured narrative review using a comprehensive literature search strategy was conducted using PubMed, Scopus, Ovid MEDLINE, and Web of Science, combining terms related to oral cancer, tongue, young patients aged ≤ 45 years, females, incidence, and risk factors. Of 653 records identified, 19 studies met the inclusion criteria after exclusion of non-English articles, conference abstracts, animal studies, and non–oral tongue reports. Population-based and institutional data from North America, Europe, Asia, and Australia consistently report increasing OTSCC incidence among young women, in some regions surpassing rates observed in age-matched men. Many affected patients are non-smokers, non-drinkers, and human papillomavirus (HPV)–negative. Proposed non-traditional contributors include genetic susceptibility, family history of malignancy, hormonal influences, early-life carcinogen exposure, chronic mucosal irritation, metabolic comorbidities, environmental factors, and possible misclassification of HPV-related base-of-tongue tumors. Molecular findings suggest distinct patterns of TP53 alterations and chromosomal instability in younger patients. The growing burden of OTSCC in young women underscores the need for improved early detection and multi-institutional molecular studies to clarify mechanisms and inform tailored prevention and treatment strategies.