What is cancer?

This series of articles aims to enhance the healthcare team awareness of the importance of early detection and management

of orofacial signs and symptoms of cancers and their treatment, and of prevention of the disease.

 

 

Cancer is caused by DNA mutations, which lead to altered cell proteins. Several DNA mutations are necessary before the affected cells change appearance and behaviour to a recognisably pre- or potentially malignant cell characterised by an ability to proliferate in a lesscontrolled fashion than normal (they become autonomous). This is seen under the microscope as

dysplasia – disordered cell size and arrangement, with abnormal cell divisions (mitoses).

 

This can transform to cancer, which is characterised by epithelial cell (keratinocyte) invasion across basement membranes into underlying tissues (figure 1). Ultimately, cancer spreads via lymphatics and blood (metastasis) to lymph nodes, bone, brain, liver and elsewhere.

 

 

DNA mutations do occur spontaneously, but the rate of mutations is increased by various cancer risk factors. Tobacco, alcohol and betel are the main oral cancer risk factors but human papillomaviruses (HPV) play a role in oropharyngeal cancer.

 

The main modifiable lifestyle factors, most of which are used as they are addictive, are tobacco and alcohol. In some cases,

betel, radiation (such as sunlight, ionising), infections (for example HPV and other microbes), or other factors may be responsible. There is protective benefit from a healthy immune system and from diets rich in fruit and vegetables.

 

Environmental and genetic factors may also play a role but are generally less important than the modifiable lifestyle factors. For example, protective mechanisms that may fail and predispose to cancer include genes for enzymes that degrade carcinogens (cancercausing chemicals); genes that repair DNA mutations; genes that repair damaged cells or kill cancerous cells (tumour suppressor genes; TSGs); and genes for immune defences. Some other genes (oncogenes) predispose to cancer.

 

Body		URL
British Association of Head and Neck Oncologists	BAHNO	http://www.bahno.org.uk/
Cochrane Collaboration	Cochrane	http://www2.cochrane.org/reviews/en/subtopics/84.html
Cancer Research UK	CRUK	http://www.openuptomouthcancer.org/index.htm
National Institute of Health and Clinical Excellence	NICE	http://www.nice.org.uk/Guidance/CSGHN
National Institutes for Dental and Craniofacial Research	NIDCR	http://www.nidcr.nih.gov/oralhealth/topics/oralcancer/detectingoralcancer.htm

Table 1: OSCC detail from various bodies.

 

	ICD–9	ICD–10
Lip	140	C00
Tongue	141	C01–02
Gum	143	C03
Floor of mouth	144	C04
Other and unspecified mouth	145	C05–06
Salivary gland	142	C07–08
Oro-, naso-, and hypopharynx Other and ill-defined sites of lip, oral cavity and pharynx	146–149	C09–14

Table 2: WHO International Classification of Diseases.

How does cancer develop?

 

Oncogenesis (carcinogenesis) - is the progression from a normal epithelial cell (keratinocyte) to a pre-malignant or a potentially malignant cell - characterised by a series of steps leading to the aberrant expression and function of molecules regulating cell signalling, growth, survival, motility, angiogenesis (blood vessel proliferation), and cell cycle control.

 

Cell cycle control is disturbed particularly by oncogenes for example, (the epidermal growth factor receptor [EGFR]) gene overexpression or over-activity - which may thus be potential targets for cancer therapy. On the other hand, tumour suppressor genes (TSGs) such as P16 help cell protection but, if defective, can impair cancer protection. Microarray DNA

technology has shown that changes in many genes can be involved in oncogenesis.

 

 

Oral cancer is the largest group of head and neck cancers and is more common than cancers of:

• Bone
• Brain
• Cervix
• Liver
• Ovaries
• Stomach
• Thyroid
• Hodgkin lymphoma

Oral cancer risk increases with age and most cases are in people aged 50 or over. In high incidence countries of the world

however, many cases are reported before the age of 40 and there is a rising incidence in young adults in many other countries (table 1). Epidemiological data show that oral cancer is increasing, and in younger patients.

 

Oral cancer is generally more common in men than women, attributable to heavier indulgence in risk habits (tobacco and alcohol) by men and exposure to sunlight (for lip cancer) as a part of outdoor occupations. However, the ratio of males to females diagnosed with oral cancer has declined and is now about 1.5:1 for the mouth and about 2.8:1 for cancer of oropharynx. Oral cancer is also a problem especially in males of lower Social and Economic Status (SES).

 

Of the many malignant neoplasms that can affect the mouth, oral squamous cell carcinoma –cancer - is the most important. Cancers of the ‘oral cavity and oropharynx’ as classified in the ICD (International Classification of Diseases) include cancers of the lip, tongue and mouth (oral cavity) [ICD-10: C00-06], and oropharynx [ICD-10: C09-C10], but excludes the salivary glands [C07-08] and other pharyngeal sites [C11- 13] (table 2). ICD-9 is shown for comparison.

 

Oral and pharyngeal cancers are the sixth leading cancers in the world and rank in the top three in high incidence areas. There is a wide geographical variation but two thirds of the cases occur in people from resource-poor countries such as in

south Asia (including Sri Lanka, India, Pakistan, Taiwan); Latin America (Brazil, Uruguay and Puerto Rico and Cuba; and Papua New Guinea, and other pacific islands in Melanesia (fig 2). In the USA, people of African heritage appear predisposed,

particularly for oropharyngeal cancers. Within the EU countries the highest male incidence rates are found in France, and Hungary, Slovakia and Slovenia. The incidence rates in Europe are higher in Eastern compared with Western, Northern or

Southern Europe.

 

In 2010, in the UK, there were 6,539 people diagnosed with 1,985 deaths. The UK rates were significantly highest in Scotland but Ireland had the highest rates. Oral cancer is also seen more frequently in UK in Asians and the racial/ ethnic disparity in oral cancer rates in the world is largely attributable to lifestyles, particularly chewing tobacco and areca nut.

 

In the UK, incidence rates are highest in Scotland; rates are also high among south Asian women and in recent/new migrants from eastern EU.

 

 

In general, prognosis decreases with advanced disease, low SES, advanced age and continuing risky lifestyles. The best outcomes for overall five year survival rates for treated oral cancers is over 90 per cent for lip cancer. This relates presumably to the very early diagnosis at this site. The five year survival rates for treated cancers of the tongue, oral cavity,

oropharynx are around 50-60 per cent. Patients usually delay seeking professional advice on average for periods up to three months after having become aware of any oral symptom that could be linked to oral cancer.