Smoking has been consistently associated with an increased risk of oral cancer but smoking patterns do not explain the geographical variation of this cancer. A possible explanation is the chewing of betel quid. Betel quid generally consists of areca nut, part of the Piper betle plant (flower stalk, leaf or stem) and slaked lime (either as a powder or paste). In India and Pakistan, tobacco and other spices are often included as well. The quid is used to produce a sense of euphoria and alertness in the user, but several lines of evidence support the suggestion that the chewing of betel quid increases the risk of oral cancer. Betel quid contains various carcinogens – it is carcinogenic in animal models and there are higher rates of oral cancer in areas where the chewing of betel quid is common. In many countries, but not Papua New Guinea, people put tobacco in the betel quid, as well as smoking it. Few studies have been able to reliably estimate the role of betel chewing (as distinct from the role of tobacco) as an independent risk in oral cancer.
A series of studies undertaken by Thomas in the 1990s and published in The Lancet, led to a possible explanation of the cause of the disease and how it could be prevented. These studies showed that although oral cancer geographically reflected the distribution of betel quid chewing, smoking was a vital co-factor. While the risk of getting oral cancer was doubled for those people who either chewed betel quid or smoked tobacco, those who did both were five times more likely to get oral cancer. In addition, slaked lime when added to the chew appears to have a crucial role in the development of mouth cancer.
The quid is used to produce a sense of euphoria and alertness
In Papua New Guinea oral cancer is predominantly a disease of lowland and coastal regions and is most common in New Ireland Province. In the highland region – where the Areca catechu palm does not fruit – low rates of oral cancer persist in spite of smoking being common. Thomas and his Papua New Guinean colleagues therefore undertook a large study in the lowlands of Papua New Guinea where betel quid use is common but, importantly, does not contain tobacco.
This study was conducted among a mostly pre-literate population (that is, a culture without a written language), which posed some particular challenges. People were interviewed in Melanesian Pidgin. Their age and the length of time they had smoked or chewed was estimated relative to key events such as the Second World War. However, assessing the frequency of smoking and betel quid chewing was more problematic as different groups of people did not necessarily use the same base for their counting system. To combat this, each person was first asked about their daily activities from waking until going to sleep. A typical day was divided into activities such as from sunrise to going fishing or hunting; coming back to work in the garden; eating and sitting around a fire in the evening. The interviewee was asked whether they chewed betel quid or smoked during each period. The specific components of the quid (eg the chewing of commercial building lime) or the type of tobacco smoked (eg most people smoked home grown, high-tar tobacco rolled in newspaper or leaves) was recorded in the local language.
Although the risk of cancer was increased with the frequency of chewing the quid, the effect of chewers smoking was greatly increased. But Thomas also looked at the role of slaked lime added to the quid and found that oral cancer in Papua New Guinea is concentrated at the corner of the mouth and cheek, which corresponds precisely with the site of application of slaked lime in most cases. Powdered slaked lime – a corrosive chemical – is applied to the chewed nut with Piper betle flower stalk at the corner of the mouth. This causes the betel quid ingredients to generate free radicals which, together with carcinogens from the tobacco smoke, cause DNA damage that cannot be repaired because of the rapid cell turnover caused by the caustic lime.
The risk of cancer increased in chewers who also smoked
Over and above the research investigating the cause of oral cancer and its prevention, the team also collaborates as surgeons. As Thomas (a head and neck surgeon) has practised in Papua New Guinea, he is very aware of the problems associated with such surgery in this remote setting. The operations required are technically difficult, both in the removal of the cancer from the mouth and the neck, and the reconstruction of the defect so that the person can swallow and speak. The team is currently establishing links with head and neck surgeons in Papua New Guinea to undertake a visit to transfer practical skills of micro-surgery applicable to local conditions.
In addition, a discussion is now taking place as to how oral cancer can best be prevented. Obviously cutting down on both chewing and smoking is likely to reduce the risk of getting oral cancer, as well as other smoking-related diseases, and Thomas believes that the chewing of commercial building lime as part of the quid should also be discouraged. However, betel quid chewing is deeply engrained in traditional practices and thus there would be wide cultural implications if its use were modified. Furthermore, a recent article in The Lancet has highlighted the problems of a deteriorating health system due to the constraints of a troubled economy. The management of this disease is not easily solved at any level.
Dr Thomas’s work in Papua New Guinea was funded by the World Health Organization and the Royal College of Surgeons of England.
Steve Thomas/Bristol Dental School