Chapter 6 Mouth cancer By Professor Crispian Scully CBE, Professor emeritus, UCL, London and Mr Nicholas Kalavrezos, Maxillofacial & Reconstructive Surgeon of The Head, Face & Neck, University College London Hospital and The Harley Street Clinic.
Introduction Cancer is caused by DNA mutations, which lead to altered cell proteins and function. Mutations can be spontaneous or caused by various mutagens such as tobacco, alcohol or viruses (Figure 1). 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 less-controlled fashion than normal (they become autonomous). The effects of these changes may be seen under the microscope as dysplasia – disordered cell size and arrangement, with abnormal cell divisions (mitoses). This can transform to cancer - characterised by malignant epithelial cells (keratinocytes) which proliferate and invade across the epithelial basement membranes as a ‘growth’ into the underlying tissues. The mass is termed a malignant neoplasm. Ultimately, the cancer spreads locally, often causing a swelling (tumour) and, via lymphatics and blood (metastasis –or ‘secondary’ growth) spreads to lymph nodes, bone, brain, liver and elsewhere. Finally, even with treatment, many cancers recur and can be fatal. People with one particular cancer are also predisposed to develop another malignant neoplasm - a second primary cancer (second primary tumour; SPT) - in the case of mouth cancer, SPTs may be in the mouth, or aerodigestive tract (pharynx, larynx, bronchi, oesophagus).
Figure 1 The early progression of cell mutation
46
What are head and neck cancers? Cancers can arise in any of the tissues or organs in the head and neck: there are over 30 different sites that can be affected (Figure 2). The mouth is the most common site in the head and neck region in which cancer develops. Cancers can develop on the lips, tongue, floor of the mouth (beneath the tongue), the buccal mucosae, the palate, the gingivae or oropharynx (Figure 3). Head and neck cancers can also affect the throat, and there are rarer cancers of the nose, sinuses, salivary glands, skin and middle ear, or arising in other tissues.
Figure 2 Head and neck anatomy
47
Figure 3 Oral anatomy showing common sites of cancer development
(A) What are mouth cancers? Mouth cancers can include:
• Lip cancer; most develop on the lower lip
• Intra-oral cancer; most develop on the lateral tongue & the floor of the mouth
• Oropharyngeal cancer; most affect the tonsils and base of the tongue.
There are also malignant tumours that arise from other structures including the salivary glands and paranasal air sinuses, or other tissues, but these cancers do not share a similar natural history and should be considered separately (Figure 4).
48
Oropharynx
Hypopharyynx
Figure 4 Sites of oropharyngeal and other cancers
(B) What are the types of mouth cancer? Cancers can be described according to the cell type where the cancer began. In the oral mucosa the most common malignancies, and nine out of 10 arise from keratinocytes, are oral squamous cell carcinomas (OSCC) which are more common:
• In older people and in men (as with most cancer)
• In people who have already had mouth or oropharyngeal cancer or potentially
malignant disorders: women have a higher risk of a SPT than men
• In people who have had some other types of cancer such as:
• Cancer of the oesophagus
• Squamous cell skin cancer
• Cervical, anal or genital cancer in women
• Cancer of the rectum in men.
49
Oral precancerous (potentially malignant) disorders include especially:
• Erythroplakia (red patches); over 75% can become cancerous
• Leukoplakia (white patches); from 3-35% can develop cancerous changes
• Submucous fibrosis; from 1- 10% can develop cancerous changes.
• Lichen planus; from 1- 3% can develop cancerous changes.
(B) What is the international classification of mouth tumours? Of the many malignant neoplasms that can affect the mouth, oral squamous cell carcinoma (OSCC) is the most important. Cancers of the ‘oral cavity and oropharynx’ as classified in the WHO International Classification of Diseases (ICD) 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 1). ICD-9 is shown for comparison.
W.H.O International Classification of Diseases
Table 1 WHO Classification
Epidemiology (B) What is the size of the mouth cancer problem? About 2 out of every 100 cancers diagnosed (2%) are mouth cancers (oral and oropharyngeal) and these are the most common cancers of the head and neck. The most common are in the tongue and mouth, collectively accounting for 60% of cases in 2010. Cancer of the lip accounts for around 6% of cases.
50
(B) What is the epidemiology of mouth cancer? Worldwide, approximately 500,000 new cases of head and neck cancer are diagnosed annually, with three quarters of cases affecting people in the resourcepoor, developing world. Factors important in mouth cancer include especially lifestyle modifiable risk factors but are also related to: • Age
Mouth cancer is more common in people over 45
• Gender
Mouth 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
• Social class
Oral cancer is a problem particularly of people of lower social and economic
status (SES), especially in males.
(B) Resource-rich populations. OSCC is the eighth most common form of cancer overall in people in developed countries, though the ranking varies a great deal among countries. The incidence is generally higher in ethnic minorities in developed countries. There is concern about an ongoing increase in younger patients and in women. The prevalence of intraoral cancer appears to be rising in many countries, especially in younger people. More than one in ten cases is now diag¬nosed in people below age 50. Cancer of the lip is uncommon in the UK, with around 340 people diagnosed with it each year. Intra-oral cancer is more common by tenfold. Around 1,900 people have been diagnosed with cancer of the tongue each year and 1,800 diagnosed with cancers affecting other parts of the mouth. There are 14 new oral cancer cases for every 100,000 males in the UK, and 7 for every 100,000 females. By 2030 it is predicted there will be 9,200 cases of oral cancer in the UK every year. The rates do not differ significantly between England, Wales and Northern Ireland for either gender. In the UK, incidence rates of mouth cancer are highest in Scotland but Ireland had higher rates; rates are also high among South Asian women and in recent/new migrants from eastern EU. (B) Is the UK epidemiology of mouth cancer changing? Since the mid-1970s, incidence rates have increased overall for all of the broad age groups, except males aged 80+ . There are likely to be several reasons for the
51
increases, including the ageing population, changing demographics and changing lifestyles such as past changes in the prevalence of major risk factors, such as heavy alcohol consumption, smoking and infection with the human papilloma virus (HPV). Chewing betel is also a risk factor for oral cavity cancer (ICD-10 C02-04 and C06) and this and shisha may have contributed to the increasing trend. The number of people being diagnosed with mouth cancer is now increasing, with notable rises in incidence in younger people and in females. Oropharyngeal carcinoma, which has risen in incidence in the same time frame has appeared in a younger, nonsmoking population. High-risk human papillomavirus (HPV) subtypes have been identified in a significant fraction of these tumours. Greater numbers of sexual partners, early age of first sexual intercourse, and high-risk sexual behaviour are emerging as risk factors for HPV-related disease independent of tobacco and alcohol abuse. (B) Is mouth cancer survival changing? The best outcome for overall 5 year survival rates for treated mouth cancers is over 90% for lip cancer, which relates presumably to the very early diagnosis at this site. The 5 year survival rates for treated cancers of the tongue, oral cavity and oropharynx however are around 50-60%. Survival rates for oral and oropharyngeal cancers have risen slightly over the last 20 years. In general, prognosis decreases with advanced disease, low SES, advanced age and continuing risky lifestyles. Mouth or oropharyngeal cancer due to HPV generally has a better outlook than in cancers not associated with HPV. Generally speaking, the earlier a cancer is found and treated, the better the outcome is likely to be (Figure 4). However, patients frequently delay seeking professional advice on average for periods up to 3 months after having become aware of any oral symptom that could be linked to mouth cancer.
Figure 4 Five year survival rates
52
(A) Risk factors (B) What are cancer risk factors? A risk factor is something that increases the chance of developing cancer. The cancer risk depends on a combination of genes, environment and modifiable aspects of our lives (Figure 5).
Figure 5 The interaction of risk factors
However, having a risk factor for cancer does not mean necessarily that cancer will develop: some people with risk factors never develop cancer, and yet other people without known risk factors can still develop cancer. Research is always trying to unravel the reasons. Anything that increases DNA mutations increases a person’s chances of developing cancer and is called a ‘cancer risk factor’. It is impossible to control mouth cancer risk factors such as gender and age. However, many other factors can be controlled – known as modifiable risk factors – and many of these relate to the lifestyle chosen. Some risk factors are definitive and others are only possible risk factors. The main known definitive risk factors for mouth cancer are using tobacco and drinking alcohol: it is thought that about 3 out of 4 head and neck cancers (75%) are linked to tobacco or alcohol use. Other risk factors include betel, radiation (e.g. sunlight, ionising), and infection with the virus human papillomavirus (HPV), which play a role in cancers at the back of the mouth (the oropharynx) oropharyngeal cancer.
53
Tobacco and alcohol are the main definitive risk factors for mouth cancers in the resource-rich world. Cigarettes and alcohol contain nitrosamines and other chemicals known to cause cancer. Sunlight exposure predisposes to lip cancer. Immune defects or immunosuppression underlie some cases of mouth cancer. Environmental and genetic factors may also play a role but are generally less important than the modifiable lifestyle risk factors. There is protective benefit from a healthy immune system and from diets rich in fruit and vegetables.
54
PROFESSIONAL DENTISTRY
Uniting the Profession
CPD E-Publications Here’s how you can benefit from quality, verifiable content...
Purchase verifiable CPD E-Publications displayed below from £59+vat
OR
Book any paid conference and receive FREE verifiable hours from the below, enough to fulfil your annual requirement.
DENTAL CPD NOW
DIGITAL DENTISTRY
IMPLANTS NOW
20 Verifiable CPD hours
6 Verifiable CPD hours
6 Verifiable CPD hours
£129+vat AVAILABLE NOW
£59+vat PRE-ORDER TODAY
£59+vat AVAILABLE NOW
A contemporary overview of dentistry in the UK for the whole dental team in a series of illustrated articles written by top authors. It features the following 7 CPD verifiable hours of core and recommended topics along with an additional 13 verifiable CPD hours:-
Update your knowledge of the
The essential resource for implantology
high-tech end of dental procedures.
practitioners. Including:
> CAD/CAM DESIGNED
> IMPLANTS & TECHNOLOGY
> MEDICAL EMERGENCIES Mike Pemerberton, Martin Thornhill, Guy Atherton
> LEGAL & ETHICAL ISSUES Len D’Cruz
> SAFEGUARDING ADULTS Elizabeth Bower et al
> SAFEGUARDING CHILDREN Jenny Harris et al
RESTORATIVE DENTISTRY e.g. CEREK. Both from the clinician and laboratory angles > COMPUTER-AIDED
IMPLANT DENTISTRY > DIGITAL RADIOGRAPHY > IMPRESSION TAKING
BY SCANNING > 3D PRINTING & HOW
IT MIGHT IMPACT ON DENTISTRY IN THE FUTURE
> ORAL CANCER Crispian Scully
> RADIOLOGY/RADIOGRAPHY Stephen Hancocks
> INFECTION CONTROL/
DECONTAMINATION Stephen Hancocks
PDF Available for use on PCs, smartphones & tablets
NEED TO TRAIN YOUR WHOLE PRACTICE? Call us for a quote on a package booking
Call: 01332 226590 Visit: professionaldentistry.co.uk
55
FEATURING CBCT SCANS & DIGITAL IMPRESSIONS Aws Alani > TAKING THE SIMPLER
IMPLANT OPTION Zaki Kanaan > IMPLANT RESEARCH UPDATE Stephen Hancocks