Aetiology of Head and Neck Cancers
Introduction: The most common head and neck malignancy is squamous cell carcinoma. It causes 95% of Head and Neck malignancy.
Tobacco and Alcohol: These two substances have been proved to play a role in the etiology of Head and Neck malignancies. Of these two substances tobacco undoubtedly plays a vital role in the etiology of squamous cell cancers of head and neck region. Positive association also exists between tobacco usage and malignancy of upper aerodigestive tracts like oesophagus and lungs.
Studies have shown that concomittent exposure to tobacco and alcohol increased the risk of Head and neck malignancy by 4 times. The risk also increases proportionally as the number of cigarettes smoked per day increases. Cessation of smoking led to a reduction in the incidence of malignancy in the head and neck region. The type of tobacco used also plays a vital role in the pathogenesis of malignancy. Air processed dark tobacco increases the risk of malignancy by 2 - 5 times when compared to light colored tobacco.
Role played by tobacco as a carcinogen: Tobacco smoke contains about 4000 different chemicals in different proportions. Out of these about 43 have been positively identified as carcinogens. These include:
1. Polycyclic hydrocarbons
3. Radio active polonium - 210
It has been demonstrated that there is a risk between the Head and neck squamous cell carcinoma subsite and the method of tobacco use (i.e. smoking, chewing and reverse smoking). Tobacco chewing increased the risk of oral cavity malignancy, while reverse smoking increased the risk of palatal malignancies.
Cannabis smoking has a greater risk of causing head and neck malignancy than smoking tobacco. This could be due to the higher concentration of coal tar and aromatic hydrocarbons when compared to tobacco smoke.
Alcohol (ethanol) is not a carcinogen perse. In combination with tobacco it potentiates the carcinogenic effects of chemicals found in tobacco. This can be attributed to the fact that alcohol is a potent solvent, and it dissolves the carcinogens released from tobacco making it easier to penetrate the body tissues. Ethanol also interferes with synthesis of retenoids, derivatives of vitamin A, the substances which are supposed to have a protective influence against the development of cancer.
Among alcohols Beer is supposed to contain nitrosamines a potent proven carcinogen. On the contrary wine is supposed to contain resveratrol which is a proven cancer chemo protective agent. So the type of alcohol consumed also has a role to play in the development of head and neck cancers. Drinkers of red wine have reduced incidence of head and neck malignancy than even tetotellars.
Figure showing etiology of head and neck cancers
Viruses: Human papilloma virus has been believed to play a role in the aetiology of head and neck cancers. The genotypes of HPV (Human papilloma virus) have been classified in to three categories (risk wise).
1. High risk: (Types 16, 18)
2. Medium: (Types 31, 33)
3. Low: (Types 6, 11)
Infact the adult type of respiratory papillomatosis is caused by low risk HPV genotype, and hence are rarely associated with malignant transformation, where as the juvenile type of respiratory papillomatosis is caused by high risk HPV genotype. Malignant transformation is common in this group.
PCR studies have isolated DNA of high risk HPV types (types 16, 18) from head and neck tumors. Highest correlation could be found in malignant tissues from oral cavity.
Another virus which has a proven etiological role in causing head and neck malignancy is Ebstein Barr virus. This virus has been clearly shown to the cause for nasopharyngeal carcinomas. Patients with nasopharyngeal carcinoma show increased titres of Ebstein Barr virus antibodies.
Sunlight: Exposure to sunlight which contains ultraviolet rays can cause development of squamous cell carcinoma of skin and lips. It can also cause development of melanoma.
Nickel and chromium refining workers who are constantly exposed to these materials have an increased incidence of laryngeal cancers. Similarly exposure to asbestos fibres have also shown to play a role in aetiopathogenesis of head and neck malignancies.
Dietary factors: are also known to play a role in the etiopathogenesis of head and neck malignancies. The classic disorder being the Patterson Brown Kelly syndrome which is characterised by iron deficiency anemia, glossitis, koilonychia, and upper oesophageal webs carrying with it a high risk of post cricoid malignancy. The risk diminishes when the patient is nutritionally supported with iron and B complex supplements.
The association between nasopharyngeal carcinoma and salted fish diet have been documented. The traditional salted fish prepared in southern china contain volatile carcinogens like N-nitrosodimethylamine and N-nitrosodiehtylamine. Both these chemicals have been shown to be carcinogenic in nature.
The association of laryngopharyngeal reflux and laryngeal cancers is still being studied. The final word is not yet out at the time of writing this article.
Genetic causes: The development of head and neck cancers involves loss of control over cell proliferation and cell death. In fact there is no control at all. This loss of control at least partly has been attributed to be faulty genes. The regulation of growth and proliferation of all the cell types in the body is known to be controlled by 40 known proteins that regulate the cell cycle. These regulator proteins are known to be products of proto oncogenes and tumor suppressor genes. Under normal conditions these genes work in a coordinated manner creating a balance between cell proliferation and cell death.
Mutations of these genes may cause abnormal protooncogene activation and tumor suppresor gene inactivation causing this balance to go hayware. These mutations could be point mutations, deletions, amplification of segments of DNA, and chromosomal rearrangements.
Familial predisposition: Head and neck cancers are preventable to a great extent, if only smokers and alcoholics decide to abstain. Studies have shown hereditary predisposition for head and neck malignancies. This could be due to the way in which the carcinogens are being detoxified in these individuals. Majority of ingested carcinogens are not dangerous themselves. It is only their intermediate metabolities which are released during the detoxification process which cause the damage.
Detoxification of these carcinogenic intermediaries require an efficient enzyme system. If a particular toxic intermediary is allowed to accumulate due to some deficiency / defect in the detoxifying enzyme system it could cause irrepairable damage to the system. These active metabolites (toxic intermediaries) can bind covalently to DNA causing genetic mutations.
Polymorphism: is defined as the presence of subtly different versions of one enzyme in different individuals. Polymorphism of the enzymes involved in the metabolism of carcinogens can cause detoxification problems. One enzyme which has been extensively studied for polymorphism is N-acetyltransferase 1. This enzyme is responsible for acetylating a variety of carcinogenic aromatic amines. A variety of polymorphic genotypes of this enzyme has been identified with varying degrees of efficiency. Less efficient the enzyme more is the risk for head and neck cancer. Another enzyme studied is Glutathione S-transferase. Four different familes of this enzyme has been identified with varying efficiencies ( alpha, M, P and T).
Radiation exposure: Exposure to radiation can predispose head and neck cancers due to point mutat ions caused by it. Formerly radiation was used to treat tuberculosis of lymph nodes of neck. Patients who completed this course of treatment developed head and neck malignancy at a later date.