Defining the Earliest Stages of Cervical Cancer How do doctors know if a patient is at risk for disease? In the case of cervical cancer, physicians have the Pap test which screens patients for cervical cancer. As a part of this test, pathologists examine cervical cells under a microscope to check for abnormal cell shape and size. Tissues from this test can be used to identify precancerous stages of cervical disease often before patients show symptoms. The ability to monitor patients for early signs of cervical cancer is fundamental to diagnosis and treatment, and has helped improve rates of patient survival and remission. Her research formed a cornerstone of cervical cancer diagnosis and treatment planning. In order to fully appreciate what Dr. Stern accomplished over her decades-long career, it is important to understand the role of cytopathology in cervical cancer studies as it developed from the 1950s into the twenty first century. *** Today, if abnormal cells are found from the Pap test, they can easily be defined as pre-cancerous or cancerous, and further ranked by stage depending on results of additional biopsies. These pre-cancerous stages are termed dysplasia, or cervical intraepithelial neoplasia (CIN), and are included in textbooks or journal articles on cervical cancer diagnosis. Although dysplasia itself is not cancer, these small changes in cell structure are a strong indicator of abnormal tissue growth that may lead to cancer if left unchecked. Dr. Stern’s findings were a major advance in the field of cervical cancer and helped establish the field of cytopathology. For the first time, physicians had a more effective cancer screening method to identify patients at various stages and initiate treatment in a timely manner. (see Figure 1). Dr. Stern realized that the Pap test presented a unique opportunity to fully characterize all stages of cervical cancer development. Cervical cancer is usually a slowly developing disease, and even in the 1950s it was known that cervical cancer can take decades to fully develop into a tumor and cause symptoms. By only focusing on cervical cancer stages that have already formed tumors, physicians were missing a wealth of potentially relevant data that could help them diagnose patients at even earlier stages. Dr. Stern and other researchers had noted the small changes in cervical cell shape and size in patients who did not display any symptoms and did not have treatable cancer. But Dr. Stern hypothesized that these cellular abnormalities could be useful markers in at-risk patients. Many physicians were still skeptical of using cellular changes as a method to diagnose cancer, much less characterize pre-cancerous stages not causing physical symptoms. Dr. Stern’s ideas about dysplasia and the potential applications of cytopathology were considered radical at the time. Dr. Stern’s career spanned more than three decades, and during this time her lab conducted multiple long-term studies in Los Angeles County. Thousands of patients were examined from different racial and socioeconomic backgrounds for varying periods of time, up to 10 years in some cases [1-7]. The central conclusion of this exhaustive work confirmed her hypothesis. Patients that developed cervical cancer first displayed pre-cancerous cellular abnormalities (dysplasia) in Pap tests. These studies are also inextricably linked to her work on the birth control pill, public health, and improvement of the Pap test which are detailed on the other pages of this site. *** Although Dr. Stern published dozens of papers on this topic, she faced significant pushback in the early years of her work. Nevertheless, by the time she passed away in 1980, dysplasia was increasingly recognized as a warning sign of cervical cancer. Furthermore, cytopathology had become a widely accepted area of research and today is a standard method for cancer diagnosis. Figure 1 outlines the impact of her work on how the Pap test is used to identify patients with pre-cancerous cells in modern medicine. REFERENCES: 1. Stern E. Epidemiology of dysplasia. Obstet Gynecol Surv. 1969;24(7 Pt 2):711-23. PubMed PMID: 5212425. 2. Stern E. Cytological screening for cervical cancer; comparative findings in a 6 year survey of a well population. Cancer. 1958;11(1):122-6. PubMed PMID: 13500307. 3. Stern E. Rate, stage, and patient age in cervical cancer. An analysis of age specific discovery rates for atypical hyperplasia, in situ cancer, and invasive cancer in a well population. Cancer. 1959;12:933-7. PubMed PMID: 13834430. 4. Stern E. Cytohistopathology of cervical cancer. Cancer Res. 1973;33(6):1368-78. PubMed PMID: 4718680. 5. Stern E, et al. A cytological scale for cervical carcinogenesis. Cancer Res. 1974;34(9):2358-61. PubMed PMID: 4843536. 6. Stern E, Neely PM. Dysplasia of the Uterine Cervix. Incidence of Regression, Recurrence, and Cancer. Cancer. 1964;17:508-12. PubMed PMID: 14136534. 7. Stern E, Neely PM. Carcinoma and Dysplasia of the Cervix: A Comparison of Rates for New and Returning Populations. Acta Cytol. 1963;7:357-61. PubMed PMID: 14074943.