Georgios Nikolaou Papanikolaou (or George Papanicolaou /ppnkla/ ; Greek: . ; 13 May 1883 – 19 February 1962) was a Greek pioneer in cytopathology and early cancer detection, and inventor of the “Pap smear“.
After studying medicine in Greece and Germany, he emigrated in 1913 to the United States. He first reported that uterine cancer cells could be detected in vaginal smears in 1928, but his work was not widely recognized until the 1940s. An extensive trial of his techniques was carried out in the early 1950s. In 1961, he was invited to the University of Miami to lead and develop the Papanicolaou Cancer Research Institute there.
Born in Kymi, Greece, Papanikolaou attended University of Athens, where he studied literature, philosophy, languages and music. Urged by his father, he pursued a medical degree, which he received in 1904. Afterwards, he was conscripted into military service. When his obligation ended in 1906, he returned to Kymi to practice medicine with his father. In 1907, he began studying under Ernst Haeckel at University of Jena for one semester before moving to University of Freiburg, where he was supervised by August Weismann. Again he left after one semester, this time to join University of Munich, from which he graduated with a doctoral degree in zoology in 1910. Afterwards, Papanikolaou returned to Athens and married Andromahi Mavrogeni. He then departed for Monaco, where he worked for the Oceanographic Institute of Monaco, participating in the Oceanographic Exploration Team of the Prince of Monaco (1911).
He first reported that uterine cancer could be diagnosed by means of a vaginal smear in 1928, but the importance of his work was not recognized until the publication, together with Herbert Frederick Traut (1894-1963), of Diagnosis of Uterine Cancer by the Vaginal Smear in 1943. The book discusses the preparation of vaginal and cervical smears, physiologic cytologic changes during the menstrual cycle, the effects of various pathological conditions, and the changes seen in the presence of cancer of the cervix and of the endometrium of the uterus. He thus became known for his invention of the Papanicolaou test, commonly known as the Pap smear or Pap test, which is used worldwide for the detection and prevention of cervical cancer and other cytologic diseases of the female reproductive system.
The fact that malignant cells could be seen under the microscope was first pointed out in a book on diseases of the lung, by Walter Hayle Walshe (1812-92), professor and physician to University College Hospital, London, in 1843. This fact was recounted by Papanikolaou.
In 1928, Papanikolaou told an incredulous audience of physicians about the noninvasive technique of gathering cellular debris from the lining of the vaginal tract and smearing it on a glass slide for microscopic examination as a way to identify cervical cancer. That year, he had undertaken a study of vaginal fluid in women, in hopes of observing cellular changes over the course of a menstrual cycle. In female guinea pigs, Papanicolaou had already noticed cell transformation and wanted to corroborate the phenomenon in human females. It happened that one of Papanicolaou’s human subjects was suffering from uterine cancer.
Upon examination of a slide made from a smear of the patient’s vaginal fluid, Papanicolaou discovered that abnormal cancer cells could be plainly observed under a microscope. “The first observation of cancer cells in the smear of the uterine cervix,” he later wrote, “gave me one of the greatest thrills I ever experienced during my scientific career.”
The Romanian physician Aurel Babe made similar discoveries in the cytologic diagnosis of cervical cancer. He discovered that if a platinum loop was used to collect cells from a woman’s cervix, and the cells were then dried on a slide and stained, it could be determined if cancer cells were present. This was the first screening test to diagnose cervical and uterine cancer. Babe presented his findings to the Romanian Society of Gynaecology in Bucharest on 23 January 1927. His method of cancer diagnosis was published in a French medical journal, Presse Mdicale, on 11 April 1928, but it is unlikely that Papanicolaou was aware of it. Moreover, the two techniques are different in their design. Therefore, although Babe’s publication preceded Papanicolaou’s, the design of the Pap test belongs to Papanicolaou since he had already tried it in 1925 in “Women’s Hospital”. Recent papers have proven that Babe’s method was different from Papanicolaou’s and that the paternity of the Pap test belongs solely to Papanicolaou. Despite this, it must be said that O’Dowd and Philipp believe that Babe was the true pioneer in the cytologic diagnosis of cervical cancer, and in a spirit of recognition and fairness, in Romania, cervical testing is referred to as the Mthode Babe-Papanicolaou in honor of Babe.
At a 1928 medical conference in Battle Creek, Michigan, Papanicolaou introduced his low-cost, easily performed screening test for early detection of cancerous and precancerous cells. However, this potential medical breakthrough was initially met with skepticism and resistance from the medical community. Papanicolaou’s next communication on the subject did not appear until 1941 when, with gynecologist Herbert Traut, he published a paper on the diagnostic value of vaginal smears in carcinoma of the uterus. This was followed two years later by an illustrated monograph based on a study of over 3,000 cases. In 1954, he published another memorable work, the Atlas of Exfoliative Cytology, thus creating the foundation of the modern medical specialty of cytopathology.
In 1978, Papanikolaou’s work was honored by the U.S. Postal Service with a 13-cent stamp for early cancer detection.