Joint association of body mass index and waist circumference with head and neck cancer mortality risk in Asian population

Background: Low body mass index (BMI) has been linked to higher head and neck cancer (HNC) mortality, but the roles of general and central obesity in Asian populations are unclear. Most epidemiologic studies have evaluated BMI or waist circumference (WC) separately. We investigated the joint associations of BMI and WC with HNC mortality in Asian prospective cohorts. Methods: We conducted a pooled analysis of population-based cohorts in the Asia Cohort Consortium with follow up for cause specific HNC mortality. BMI (kg/m 2 ) was categorized using Asia-Pacific cut offs (<18.5, 18.5-22.9, 23.0-24.9, 25.0-27.4, 27.5-29.9, ≥30), and WC into sex specific quintiles and WHO obesity thresholds (≥90 cm in men, ≥80 cm in women). We also constructed joint BMI-WC and BMI-smoking categories. Multivariable Cox models estimated hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for age, sex, smoking status, alcohol intake, cohort, diabetes, and hypertension, with additional adjustment for height in WC models; analyses were stratified by smoking. Results: Compared with normal BMI (18.5-22.9 kg/m 2 ), underweight participants (<18.5) had more than a two fold higher risk of HNC mortality (HR 2.19, 95% CI 1.75-2.74), whereas those with BMI 27.5-29.9 had lower risk (HR 0.53, 95% CI 0.37-0.77), and intermediate categories showed similar inverse associations. WC showed a parallel inverse pattern; compared with the lowest quintile, higher quintiles had lower HNC mortality (e.g. Q4 HR 0.49, 95% CI 0.33-0.72; p trend<0.01). In smoking stratified analyses, underweight remained strongly associated with HNC mortality in both never smokers (HR 2.56, 95% CI 1.92-3.40) and smokers (HR 1.73, 95% CI 1.19-2.52). Joint BMI-smoking models using never smokers with normal BMI as the reference showed markedly elevated risk among underweight smokers (HR 3.76, 95% CI 2.53-5.60) and excess risk among normal BMI smokers (HR 2.19, 95% CI 1.70-2.83). In joint BMI-WC categories, underweight individuals with normal WC had higher HNC mortality (HR 2.29, 95% CI 1.47-3.56), whereas those with BMI ≥30.0 and normal WC had lower risk (HR 0.67, 95% CI 0.47-0.96); adding WC did not materially change BMI-HNC associations. Conclusion: In these Asian cohorts, smaller body size-low BMI and small WC-was consistently associated with higher HNC mortality, whereas overweight and moderate obesity were associated with lower mortality. BMI was a stronger predictor than WC, suggesting that overall body mass may be more relevant than central adiposity for HNC mortality. These findings highlight the importance of incorporating baseline nutritional status and smoking history into risk stratification and survivorship care.