Mary Papanicolaou, the woman whose tireless efforts paved the way for cervical screening

Mary Papanicolaou's legacy stands as a testament to her extraordinary dedication, making her an awe-inspiring figure and a source of gratitude for her pivotal role in the advancement of science and women's health

While the Pap test bears her husband’s name, it was Mary Papanicolaou who played an instrumental role in providing the crucial samples that shaped this life-saving screening method.

In a special tribute piece, the ABC listed the remarkable contributions of the unsung hero whose decades-long dedication laid the foundation for cervical cancer screening.

Mary’s steadfast commitment involved undergoing vaginal tests on a daily basis for over 20 years. Her unwavering participation, alongside her pathologist husband George, led to the development of the Papanicolaou or Pap test that revolutionized cervical cancer screening.

Karen Canfell, director of the Daffodil Centre and chair of Cancer Council Australia’s Cancer Screening and Immunisation Committee, recognizes the significance of Mary’s contribution, describing it as equally vital as George’s. Speaking to the ABC, Canfell stressed that the Pap test, thanks to the foundational work of Mary and George, has undeniably saved countless lives and deserves recognition for its extraordinary impact.

But how did Mary, the daughter of a Greek army colonel, become the central figure in one of the world’s most successful cancer screening programs? What is her enduring legacy?

Who was Mary Papanicolaou

Mary, originally named Andromache, was born in 1890 into the Mavroyeni family, a long line of military heritage. Her great-grandmother had fought valiantly for Greece’s liberation from the Ottoman Empire decades prior. Andromache, meaning “a woman fighting alongside men” in Greek, aptly encapsulates her inner strength and resilience, as highlighted by diagnostic cytologist Nikolaos Chantziantoniou in the Journal of the American Society of Cytopathology.

During her childhood, Mary’s family spent summers at a beach house near Athens, where they formed a close bond with their neighbors, the Papanicolaou family. It was there that Mary, preferring to go by her chosen name, first encountered George. Their paths crossed again when Mary was 20, and George was immediately captivated by her allure, cultural refinement, and education.

The couple eloped and later embarked on a new journey in New York City, armed with only $250 and limited fluency in English. Mary secured a job sewing buttons at a department store, while George sold rugs and performed odd jobs like playing the violin in restaurants and cafes. Despite their humble beginnings, George managed to secure a position as an assistant anatomist at Cornell Medical College in 1914.

Mary soon joined him as a laboratory technician, although she had to volunteer her services due to Cornell’s policy against employing spouses. This marked the beginning of a scientific pursuit that would forever transform women’s health.

Mary Papanicolaou’s role in human research and the development of the Pap Test

Mary Papanicolaou played a pivotal role in advancing the research from guinea pigs to human subjects and the subsequent development of the Pap test. The laboratory where George and Mary worked was led by Charles Stockard, an anatomist and eugenicist who was investigating the effects of alcohol on guinea pig chromosomes.

George spearheaded a project to explore the role of X and Y chromosomes in determining guinea pig sex.

To collect guinea pig eggs before ovulation, George needed to determine the animals’ reproductive cycle, which required sacrificing them.

Drawing inspiration from the fact that guinea pigs menstruated, George wondered if vaginal fluid samples could provide insights into their reproductive cycle. Using a small speculum, he collected daily samples of guinea pig vaginal fluid, examining them under a microscope.

The samples included cells from the cervix’s surface, known as the epithelium.

Over time, George observed distinct patterns in the size and shape of these cells that precisely correlated with ovulation. The findings were published in 1917.

George’s next goal was to apply the same methodology to humans, but as he lacked the required license to access human subjects, he turned to Mary.

This marked the beginning of Mary’s remarkable 21-year commitment to daily testing. Not only did she willingly provide vaginal fluid samples every day, but she also processed and stained her own samples in the lab to enhance the visibility of certain cell components.

This allowed George to track cellular changes in Mary’s reproductive cycle throughout her life, from her fertile years to menopause.

Mary eventually recruited friends to participate, and a larger trial involving women from the New York Women’s Hospital commenced in 1925.

Samples were collected using a thin glass tube resembling a slender turkey baster, which extracted a small amount of fluid.

This method proved effective and convenient, as George and his collaborator Herbert Traut noted in their 1943 book, “Diagnosis of Uterine Cancer by Vaginal Smears.”

Her and the volunteers’ dedication and contributions paved the way for the advancement of cervical cancer screening.

Unfortunately, one of the volunteers in the trial eventually developed cervical cancer, highlighting the importance of early detection through the Pap test.

Dr. George Nicholas Papanikolaou (1883 – 1962). Photo: AHEPA Archives Facebook

Advancements in cervical screening and the transition to HPV testing

The discovery of pre-cancerous changes in cervical cells marked a significant breakthrough for the Papanicolaous.

However, it took a decade for the medical community to recognise the value and effectiveness of their diagnostic technique.

Convincing skeptics of its worthiness proved to be a prolonged endeavour.

The modern-day Pap test differs slightly from Mary’s daily routine.

It involves inserting a speculum to access the transformation zone of the cervix, which is susceptible to virus-induced changes that can lead to cancer.

Australia introduced Pap tests in the 1960s, but it wasn’t until 1991 that the National Cervical Screening Program started offering free biennial tests to sexually active individuals with a cervix aged 20 to 69, later including 18- and 19-year-olds.

The incidence and mortality rates of cervical cancer have significantly decreased as a result.

The introduction of self-collected cervical screening is the latest advancement.

This method, reminiscent of the vaginal fluid sampling of a century ago, now involves inserting a swab into the vagina, swirling it for 20 to 30 seconds, and placing it in a container. The swab is then analysed for the presence of HPV DNA.

This testing method allows for the identification of potential indicators of cervical cancer at an earlier stage than the Pap test. It is more accurate, requiring screening every five years instead of the previous two-year interval, and easier to administer with the use of highly sensitive machines.

Megan Smith, an epidemiologist at the Daffodil Centre, explained that “this new technique focuses on detecting the virus that causes pre-cancerous changes, rather than directly examining cells. Its increased accuracy and simplicity make it more accessible for implementation in areas where screening has traditionally been challenging.”

The ongoing advancements in cervical screening techniques demonstrate the remarkable progress made since Mary Papanicolaou’s daily dedication to testing.

The shift towards HPV testing holds the potential to further enhance early detection and contribute to the prevention of cervical cancer.

Mary Papanicolaou’s lasting legacy in cervical cancer prevention

After over 40 years of work at Cornell, both George and Mary retired in 1957.

While George gained some recognition, including multiple Nobel Prize nominations, Mary’s efforts remained unpaid throughout her career.

Tragically, in 1962, George passed away shortly after assuming the directorship of the Cancer Research Institute of Miami. However, Mary continued to receive awards on behalf of her late husband, and she herself was also honoured.

In 1969, the American Cancer Society presented her with a special citation, acknowledging her ability to recognise greatness and serve it.

Mary remained dedicated to supporting cancer research until her passing on October 13, 1982, at the age of 92.

Her extraordinary commitment and sacrifices in the field of science, including becoming a subject and volunteering for research, choosing not to have children, and dedicating herself to the partnership with George, demonstrated her profound devotion to advancing women’s health.

Speaking to the ABC, Professor Karen Canfell emphasised the immeasurable importance of Mary’s contribution to cervical cancer prevention. She admires the obstacles Mary overcame and the sacrifices she made to pursue a career in science and achieve significant outcomes in women’s health.

“For a woman like me who’s working in the modern era in science, there may have been some difficulties, but nothing like what Mary confronted and what she sacrificed to have a career in science and to make this contribution at every level,” she said.

“She became a subject, she worked as a volunteer, she elected not to have children, and it was all to work in this partnership towards an outcome in health that is so important for women generally.” Professor Deborah Bateson echoed this sentiment, recognising Mary’s remarkable generosity and the devotion she exhibited in advancing scientific progress despite women’s’ position back then.

“It was a tremendous act of great generosity, really,” Prof. Bateson stressed. “When I think about it, I’m in awe, and I’m grateful of that devotion that she gave to this advancement of science — this fantastic, well-educated woman, who perhaps wasn’t able to work to her full capacity because of the limitations and challenges at the time.”

For more information on the legacy of the Papanicolaous and Mary’s efforts visit the official ΓΕΩΡΓΙΟΣ Ν. ΠΑΠΑΝΙΚΟΛΑΟΥ website.