For millions of people across South and South-East Asia, chewing betel nut is a daily routine. Whether consumed as gutkha, betel quid or paan, it’s a habit deeply rooted in culture, tradition and social customs (Singh et al., 2020).
But alongside its cultural significance lies a serious and growing public health challenge.
More than 600 million people worldwide regularly chew areca nut, making it one of the most widely used psychoactive substances globally, with the highest prevalence in South and South-East Asia, particularly in countries such as India, Bangladesh, Singapore, and across parts of Southeast Asia (Murphy & Herzog, 2015). In many communities, use begins early in life and continues daily for decades, contributing to a sustained regional burden of oral disease.
The continued availability and widespread use of areca nut mean that this burden is unlikely to disappear in the near future. According to the United Nations Food and Agriculture Organization (FAO), global areca nut production almost doubled between 2002 and 2019, increasing from approximately 995,000 to 1.8 million metric tonnes (Wu et al.,2025). This growth reflects the ongoing scale of areca nut use across major consuming regions and reinforces the need for effective prevention and earlier intervention strategies.
Unlike many lifestyle risk factors, the link between areca nut and oral cancer is no longer debated. The International Agency for Research on Cancer (IARC) classifies areca nut as a Group 1 carcinogen, placing it in the same category as tobacco and asbestos (Warnakulasuriya & Chen, 2022).
More Than a Risk Factor
What makes betel nut use particularly challenging in South Asia is not only its prevalence, but the long-term biological impact of chronic exposure.
Regular chewing exposes the oral tissues to its principal alkaloid arecoline, triggering oxidative stress, chronic inflammation and changes to the normal repair processes of the oral mucosa. Over time, these repeated insults can lead to oral potentially malignant disorders, with a risk of progression to oral cancer (Yu et al., 2026b)
For clinicians across South and South-East Asia, these conditions are encountered far more frequently than in many Western countries, making early management a significant part in reducing the region’s oral cancer burden (Rai et al., 2022)
Rethinking Intervention
Oral cancer remains one of the most common cancers in several Asian countries, and despite advances in surgery and oncology, outcomes are still closely linked to how early the disease is identified and managed.
Today, patients with potentially malignant lesions are often monitored over time or treated surgically where appropriate. While these approaches remain the standard of care, they also highlight an opportunity to rethink how we manage disease before it becomes invasive (Kumari et al.,2022).
As our understanding of oral carcinogenesis continues to improve, so too does interest in therapies designed specifically for the precancerous stage.
Innovation Beyond Detection
Much of the conversation around oral cancer has focused on earlier diagnosis. However, diagnosis alone is only part of the challenge.
The next question is what happens after a suspicious lesion is identified:
Can treatment be delivered locally? Can intervention occur earlier? Can progression be reduced while preserving healthy tissue?
These are the questions driving innovation in oral oncology.
LightOx’s lead candidate, LXD191, is a topical gel applied directly to early-stage oral lesions. Once activated with a handheld light device (like dental curing lights), the compound becomes active only in the illuminated area, allowing clinicians to treat the abnormal tissue locally. Preclinical studies have shown that LXD191 can effectively induce cell death in abnormal tissue, while helping minimise damage to surrounding structures.
While progressing towards clinical evaluation, this reflects a broader shift in oncology towards therapies that intervene earlier in the disease pathway, before invasive cancer develops.
Improving Outcomes Through Earlier Action
Betel nut-associated oral disease remains a significant healthcare challenge across South and South-East Asia, but it is also an area where scientific innovation has the potential to make a meaningful impact.
Alongside prevention, public health initiatives and routine screening, there is growing recognition that earlier therapeutic intervention could play an important role in improving patient outcomes.
As researchers continue to deepen our understanding of oral carcinogenesis, the opportunity is no longer simply to detect disease earlier but to change what happens next.
References
Food and Agriculture Organization of the United Nations. (n.d.). FAOSTAT: Crops and livestock products – Areca nuts production data. FAO. https://www.fao.org/faostat/
Kumari, P., Debta, P., & Dixit, A. (2022). Oral Potentially Malignant Disorders: Etiology, Pathogenesis, and Transformation Into Oral Cancer. Frontiers in pharmacology, 13, 825266. https://doi.org/10.3389/fphar.2022.825266
Murphy, K. L., & Herzog, T. A. (2015). Sociocultural Factors that Affect Chewing Behaviors among Betel Nut Chewers and Ex-Chewers on Guam. Hawai’i journal of medicine & public health : a journal of Asia Pacific Medicine & Public Health, 74(12), 406–411.
Rai, P., Ng, A., Intekhab, I., Sim, Y. F., Lai, C. W. M., & Loh, J. (2022). Oral cancer in Asia – a systematic review. Advances in Oral and Maxillofacial Surgery, 8, 100366. https://doi.org/10.1016/j.adoms.2022.100366
Singh, A., Dikshit, R., & Chaturvedi, P. (2020). Betel Nut Use: The South Asian Story. Substance use & misuse, 55(9), 1545–1551. https://doi.org/10.1080/10826084.2020.1753772
Warnakulasuriya, S., & Chen, T. H. H. (2022). Areca Nut and Oral Cancer: Evidence from Studies Conducted in Humans. Journal of dental research, 101(10), 1139–1146. https://doi.org/10.1177/00220345221092751
Wu, N., Roberts, T. J., Apana, N., Venkatesh, S., Deville, N., Pineda, E., Zhang, S., Pathak, M., Taparra, K., & Moss, W. J. (2025). Areca nut-related oral cancer awareness in adults: A meta-analysis. Journal of Cancer Policy, 46, 100649. https://doi.org/10.1016/j.jcpo.2025.100649
Yu, N., Cai, W., Zhang, C., Cai, Q., Zhang, Z., Hu, Y., Sun, Y., Yin, K., Ren, F., Chang, K., Jin, M., Li, D., Zhang, L., Wu, H., & Li, M. (2026b). The multistep progression of areca nut-induced oral cancer: a mechanistic roadmap from pathogenesis to precision therapy. Life Medicine, 5(2), lnag011. https://doi.org/10.1093/lifemedi/lnag011
