Pathway to the Papanicolaou smear: The development of cervical cytology in twentieth-century America and implications in the present day

George Papanicolaou, a Greek immigrant and cytopathologist, was responsible for what is now colloquially known as the “Pap smear”—undoubtedly one of the greatest advances in medicine and public health of the last century. However, his landmark research on the development of cervical cytology for the detection of precancerous lesions of the cervix (“New Cancer Diagnosis,” 1928) made a rather inauspicious debut in an unlikely venue: John Harvey Kellogg's Third Race Betterment Conference—a meeting devoted to the furtherance of the concept and implementation of eugenics. Herein, we discuss the stark juxtaposition of Papanicolaou's landmark discovery amid the pseudoscience of the third Race Betterment Conference. We discuss the latency of Papnicolaou's discovery–its potential implications unrealized–until co-publication with Herbert Traut, which catapulted Papanicolaou's research to the scientific foreground. This gave rise to public health initiatives aimed at establishing the Pap smear as a screening tool. We further delineate the progress made in recent decades with the identification of HPV as the etiological agent for cervical cancer, and the subsequent development of the HPV vaccine, and discuss ongoing research in the present day. In this way, we hope to provide a background and historical context for the development of the Pap smear.