For decades, women around the world have made the annual pilgrimage to their doctor for the dreaded but potentially life-saving Papanicolaou test, a gynecological exam to screen for cervical cancer named for Georgios Papanicolaou, the Greek immigrant who developed it.
The Pap smear, as it is commonly known, is credited for reducing cervical cancer mortality by 70% since the 1960s; the American Cancer Society (ACS) still ranks the Pap as the most successful screening test for preventing serious malignancies. Nonetheless, the agency, as well as other medical panels, including the US Preventive Services Task Force and the American College of Obstetrics and Gynecology are making a strong push to replace the Pap with the more sensitive high-risk HPV screening test for the human papillomavirus virus, which causes nearly all cases of cervical cancer.
So, how was the Pap developed and how did it become the gold standard of cervical cancer detection for more than 60 years?
Born on May 13, 1883, on the island of Euboea, Greece, Georgios Papanicolaou attended the University of Athens where he majored in music and the humanities before earning his medical degree in 1904 and PhD from the University of Munich six years later. In Europe, Papanicolaou was an assistant military surgeon during the Balkan War, a psychologist for an expedition of the Oceanographic Institute of Monaco and a caregiver for leprosy patients.
When he and his wife, Andromache Mavroyenous (Mary), arrived at Ellis Island on October 19, 1913, the young couple had scarcely more than the $250 minimum required to immigrate, spoke no English and had no job prospects. They worked a series of menial jobs--department store sales clerk, rug salesman, newspaper clerk, restaurant violinist--before Papanicolaou landed a position as an anatomy assistant at Cornell University and Mary was hired as his lab assistant, an arrangement that would last for the next 50 years.
Papanikolaou would later say the discovery "was one of the greatest thrills I ever experienced during my scientific career."
In his early research, Papanikolaou used guinea pigs to prove that gender is determined by the X and Y chromosomes. Using a pediatric nasal speculum, he collected and microscopically examined vaginal secretions of guinea pigs, which revealed distinct cell changes connected to the menstrual cycle. He moved on to study reproductive patterns in humans, beginning with his faithful wife, Mary, who not only endured his almost-daily cervical exams for decades, but also recruited friends as early research participants.
Writing in the medical journal Growth in 1920, the scientist outlined his theory that a microscopic smear of vaginal fluid could detect the presence of cancer cells in the uterus. Papanikolaou would later say the discovery "was one of the greatest thrills I ever experienced during my scientific career."
At this time, cervical cancer was the number one cancer killer of American women but physicians were skeptical of these new findings. They continued to rely on biopsy and curettage to diagnose and treat the disease until Papanicolaou's discovery was published in American Journal of Obstetrics and Gynecology. An inexpensive, easy-to-perform test that could detect cervical cancer, precancerous dysplasia and other cytological diseases was a sea change. Between 1975 and 2001, the cervical cancer rate was cut in half.
Papanicolaou became Emeritus Professor at Cornell University Medical College and received numerous awards, including the Albert Lasker Award for Clinical Medical Research and the Medal of Honor from the American Cancer Society. His image was featured on the Greek currency and the US Post Office issued a commemorative stamp in his honor. But international acclaim didn't lead to a more relaxed schedule. The researcher continued to work seven days a week and refused to take vacations.
After nearly 50 years, Papanicolaou left Cornell to head and develop the Cancer Institute of Miami. He died of a heart attack on February 19, 1962, just three months after his arrival. Mary continued to work in the renamed Papanicolaou Cancer Research Institute until her death 20 years later.
The annual pap smear was originally tied to renewing a birth control prescription. Canada began recommending Pap exams every three years in 1978. The United States followed suit in 2012, noting that it takes many years for cervical cancer to develop. In September 2020, the American Cancer Society recommended delaying the first gynecological pelvic exam until age 25 and replacing the Pap test completely with the more accurate human papillomavirus (HPV) test every five years as the technology becomes more widely available.
Not everyone agrees that it's time to do away with this proven screening method, though. The incidence rate of cervical cancer among Hispanic women is 28% higher than for white women, and Black women are more likely to die of cervical cancer than any other racial or ethnicities.
Whether the Pap is administered every year, every three years or not at all, Papanicolaou will always be known as the medical hero who saved countless women who would otherwise have succumbed to cervical cancer.