Causes of Tongue Cancer
Primary Etiologic Factors
Tobacco use and alcohol consumption account for approximately 75-85% of tongue cancers, with human papillomavirus (HPV) infection emerging as an increasingly important cause, particularly for base of tongue tumors. 1
Major Risk Factors
Tobacco and Alcohol
- Tobacco smoking significantly elevates tongue cancer risk, with current smokers having a 2.73-fold increased risk (95% CI = 1.26-5.91) compared to non-smokers. 2
- Risk increases dose-dependently with both cigarettes smoked per day and lifetime pack-years of tobacco exposure. 2
- Heavy alcohol consumption, particularly spirits consumed at least 5 days per week, shows a marginally significant association (OR = 2.34,95% CI = 0.90-6.06). 2
- Combined tobacco and alcohol use demonstrates synergistic effects in increasing cancer risk. 1
Human Papillomavirus (HPV)
- HPV-16 infection carries the highest risk, with an odds ratio of 22.4 specifically for oropharyngeal squamous cell carcinoma including base of tongue. 3
- HPV-16 was detected in 68% of base of tongue cancers in one study, with 100% of never-tobacco users having HPV-positive tumors. 4
- All base of tongue tumors were associated with either tobacco use OR HPV infection, suggesting one of these factors is necessary for tumor development. 4
- HPV types 18,31, and 33 account for most remaining HPV-positive cases. 3
- The mechanism involves viral oncoproteins E6 and E7 inactivating tumor suppressor genes p53 and pRb, leading to loss of cell-cycle control. 3
Secondary Risk Factors
Weaker but Established Risk Factors 1
- Radiation exposure
- Chronic infection
- Long-term immunosuppression
- Poor oral hygiene
- Poor nutrition
- Betel nut chewing
- Ill-fitting dentures
Genetic and Hereditary Factors
Rare Inherited Syndromes 1
- Fanconi anemia
- Ataxia telangiectasia
- Bloom's syndrome
- Li-Fraumeni syndrome
- Dyskeratosis congenita
Genetic Polymorphisms
- Specific polymorphisms in genes encoding carcinogen-metabolizing enzymes have been associated with increased risk: 1
- Glutathione S-transferase (GSTM1)
- Glutathione S-transferase (GSTT1)
- Human microsomal epoxide hydrolase (EPHX1)
Clinical Implications
Risk Stratification
- Genetic counseling should be considered in cases presenting with cytopenias, young age, and family history of multiple cancers, particularly when traditional risk factors are absent. 1
- Patients with heavy tobacco and alcohol use represent the highest risk group for HPV-negative tongue cancer. 1
- Unvaccinated individuals have a 19-fold higher risk of developing oropharyngeal cancer compared to vaccinated groups, highlighting the preventive potential of HPV vaccination. 3
Important Caveat: While HPV is increasingly recognized as a cause of oropharyngeal cancers (including base of tongue), HPV-positive squamous cell carcinoma outside the oropharynx (such as anterior/oral tongue) remains rare at less than 6%. 1 The anterior tongue (oral cavity) is predominantly associated with tobacco and alcohol use rather than HPV infection. 1