This historical medical literature review aims at understanding the evolution of the medical existence of oral cancer over times, particularly better comprehending if the apparent lower prevalence of this type of cancer in antiquity is a real value due to the absence of modern environmental and lifestyle factors or it is linked to a misinterpretation of ancient foreign terms found in ancient medical texts regarding oral neoplasms. Methods: The databases MedLne, PubMed, Web of Science, Elsevier’s EMBASE.com, Cochrane Review, National Library of Greece (Stavros Niarchos Foundation, Athens) and the Library of the School of Health Sciences of the National and Kapodistrian University of Athens (Greece) were extensively searched for relevant studies published during the past century on the history of oral cancer and its treatment from antiquity to modern times, in addition to the WHO website to analyse the latest epidemiological data. In addition, we included historical books on the topic of interest and original sources. Results: Historical references reveal that the cradle of the oral oncology was in ancient Egypt, the Asian continent and Greece and cancer management was confined to an approximate surgical practice, in order to remove abnormal masses and avoid bleeding with cauterization. In the Medieval Age, little progress occurred in medicine in general, oral cancers management included. It is only from the Renaissance to modern times that knowledge about its pathophysiological mechanisms and histopathology and its surgical and pharmacological treatment approaches became increasingly deep all over the world, evolving to the actual integrated treatment. Despite the abundant literature exploring oncology in past civilizations, the real prevalence of oral cancer in antiquity is much less known; but a literature analysis cannot exclude a consistent prevalence of this cancer in past populations, probably with a likely lower incidence than today, because many descriptions of its aggressiveness were found in ancient medical texts, but it is still difficult to be sure that each single description of oral masses could be associated to cancer, particularly for what concerns the period before the Middle Ages. Conclusions: Modern oncologists and oral surgeons must learn a lot from their historic counterparts in order to avoid past unsuccessful efforts to treatment oral malignancies. Several descriptions of oral cancers in the antiquity that we found let us think that this disease might be linked to mechanisms not strictly dependent on environmental risk factors, and this might guide future research on oral cavity treatments towards strategical cellular and molecular techniques.
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