Betel quid chewing and the risk of oral and oropharyngeal cancers: a meta-analysis with implications for cancer control.

We conducted a random-effects meta-analysis of 50 publications assessing the relationship between oral/oropharyngeal cancer and chewing betel quid, with (BQ+T) or without added tobacco (BQ-T), a common practice in many parts of Asia and globally among Asian immigrants. Exposure-response, by daily amount and years of BQ chewed, was assessed using spline models. Attributable fractions (PAF%) were calculated to estimate the public health impact if BQ were no longer chewed. The meta-relative risk (mRR) for oral/oropharyngeal cancer in the Indian subcontinent was 2.56 (95%CI, 2.00-3.28; 15 studies) for BQ-T and 7.74 (95%CI, 5.38-11.13; 31 studies) for BQ+T; in Taiwan, China, the mRR for BQ-T was 10.98 (95%CI, 4.86-24.84; 13 studies). Restricting to studies that adjusted for tobacco and alcohol use had only a small effect on the risk estimates. For BQ+T in the Indian subcontinent, the mRR was much higher in women (mRR, 14.56; 95%CI, 7.63-27.76) than in men. Exposure-response analyses showed that the risk of oral/oropharyngeal cancer increased with increasing daily amount and duration (years) of chewing BQ in India and Taiwan, China. Roughly half of oral cancers in these countries could be prevented if BQ were no longer chewed (PAF%=53.7% for BQ-T in Taiwan, China; PAF%=49.5% for BQ+T in India). We demonstrate that betel quid chewing, with or without added tobacco, increases the risk of oral/oropharyngeal cancer in an exposure-dependent manner, independently of tobacco and alcohol use. Further work is needed to explain the higher risks associated with chewing BQ-T in Taiwan, China.