The term "second primary cancers" is applied to cancers that appear to be related to pre-existing treated or untreated cancers but that are in fact entities have arisen independently and not as a result of resurgence, nor as a result of metastasis of the original primary cancer. With respect to the original cancer, such cancers may justifiably be called second primary cancers. Most cancers develop in genetically susceptible persons exposed to exogenous carcinogens. Persons with rare inherited cancer susceptibility genes are at high risk of cancers, and those with genetic variants (genetic polymorphism) of specific genes encoding enzymes involved in breaking down common carcinogens, or in encoding DNA-repair proteins, though also at risk, are at significantly lower risk. Persons who have, or who have been treated for, primary carcinoma of the upper aerodigestive tract are at increased risk of developing second primary carcinomata in this region. This increased risk is most closely associated with tobacco smoking and with long-term excessive consumption of alcoholic beverages; and tobacco and alcohol used together have a synergistic effect. As primary oral squamous cell carcinoma usually develops within a field of pre-cancerised epithelium, and as treatment of the carcinoma does not necessarily eradicate the entire pre-cancerised field, because it is neither histologically detectable, nor is its extent determinable, additional cytogenetic alterations to the transformed keratinocytes in the field may give rise to second primary carcinomata in the upper-aero digestive tract.