"Non-habit associated oral squamous cell carcinoma: A systematic review"

Oral squamous cell carcinoma (OSCC), the most common oral malignancy, accounts for 80-90% of oral cancers. India bears the highest global burden, with one-third of cases worldwide. A significant proportion of OSCC in the Indian subcontinent arises in individuals without traditional risk factors such as tobacco or alcohol use, suggesting the involvement of alternative etiologic factors that remains poorly defined.

To systematically review and synthesize evidence on the demographics, lesion distribution, and potential non-habit-related risk factors of OSCC, aiming to clarify its etiopathogenesis in patients without deleterious habits such as tobacco or alcohol use.

A total of 1355 records were identified (PubMed: 268, Scopus: 393, Embase: 694), with 580 duplicates removed, leaving 775 records for screening. After exclusion, 39 studies met the criteria: 17 cohort, 8 case-control, 8 cross-sectional, and 6 case reports. Methodological quality and risk of bias was assessed independently by two reviewers using relevant Joanna Briggs Institute (JBI) Critical Appraisal Checklists.

The 39 included studies spanned a wide geographic range, with India contributing the most (n = 6). Non habit associated oral squamous cell carcinoma cases occurred at a significantly younger age (mean 45.84 vs. 63.71 years; p = 0.068) and showed a female predominance (p = 0.028). The tongue was the most frequent site. Key associations included recurrent genetic mutations, enrichment of Fusobacterium and Porphyromonas, and risk factors such as low fruit and vegetable intake, chronic mucosal trauma, immunosuppression, poor oral hygiene, passive smoking, and occupational or environmental exposure to heavy metals.

Non-habit-associated OSCC is a distinct clinical entity, often occurring in younger patients with a slight female predominance and unique risk factor patterns. Its diverse etiological spectrum including viral, microbial, dietary, immunologic, and environmental exposures highlight the importance of tailored preventive approaches. Robust high-quality research is needed to elucidate causal mechanisms and enhance early diagnosis in these cases.