Pap test

The invention: A cytologic technique the diagnosing uterine cancer,

the second most common fatal cancer in American women.

The people behind the invention:

George N. Papanicolaou (1883-1962), a Greek-born American

physician and anatomist

Charles Stockard (1879-1939), an American anatomist

Herbert Traut (1894-1972), an American gynecologist

Cancer in History

Cancer, first named by the ancient Greek physician Hippocrates

of Cos, is one of the most painful and dreaded forms of human disease.

It occurs when body cells run wild and interfere with the normal

activities of the body. The early diagnosis of cancer is extremely

important because early detection often makes it possible to effect

successful cures. The modern detection of cancer is usually done by

the microscopic examination of the cancer cells, using the techniques

of the area of biology called “cytology, ” or cell biology.

Development of cancer cytology began in 1867, after L. S. Beale

reported tumor cells in the saliva from

a patient who was afflicted

with cancer of the pharynx. Beale recommended the use in cancer

detection of microscopic examination of cells shed or removed (exfoliated)

from organs including the digestive, the urinary, and the

reproductive tracts. Soon, other scientists identified numerous striking

differences, including cell size and shape, the size of cell nuclei,

and the complexity of cell nuclei.

Modern cytologic detection of cancer evolved from the work of

George N. Papanicolaou, a Greek physician who trained at the University

of Athens Medical School. In 1913, he emigrated to the

United States.

In 1917, he began studying sex determination of guinea pigs with

Charles Stockard at New York’s Cornell Medical College. Papanicolaou’s

efforts required him to obtain ova (egg cells) at a precise

period in their maturation cycle, a process that required an indicator

of the time at which the animals ovulated. In search of this indicator,

Papanicolaou designed a method that involved microscopic examination

of the vaginal discharges from female guinea pigs.

Initially, Papanicolaou sought traces of blood, such as those

seen in the menstrual discharges from both primates and humans.

Papanicolaou found no blood in the guinea pig vaginal discharges.

Instead, he noticed changes in the size and the shape of the uterine

cells shed in these discharges. These changes recurred in a fifteento-

sixteen-day cycle that correlated well with the guinea pig menstrual

cycle.

“New Cancer Detection Method”

Papanicolaou next extended his efforts to the study of humans.

This endeavor was designed originally to identify whether comparable

changes in the exfoliated cells of the human vagina occurred

in women. Its goal was to gain an understanding of the human menstrual

cycle. In the course of this work, Papanicolaou observed distinctive

abnormal cells in the vaginal fluid from a woman afflicted

with cancer of the cervix. This led him to begin to attempt to develop

a cytologic method for the detection of uterine cancer, the second

most common type of fatal cancer in American women of the

time.

In 1928, Papanicolaou published his cytologic method of cancer

detection in the Proceedings of the Third Race Betterment Conference,

held in Battle Creek, Michigan. The work was received well by the

news media (for example, the January 5, 1928, New YorkWorld credited

him with a “new cancer detection method”). Nevertheless, the

publication—and others he produced over the next ten years—was

not very interesting to gynecologists of the time. Rather, they preferred

use of the standard methodology of uterine cancer diagnosis

(cervical biopsy and curettage).

Consequently, in 1932, Papanicolaou turned his energy toward

studying human reproductive endocrinology problems related to

the effects of hormones on cells of the reproductive system. One example

of this work was published in a 1933 issue of The American

Journal of Anatomy, where he described “the sexual cycle in the human

female.” Other such efforts resulted in better understanding of   reproductive problems that include amenorrhea and menopause.

It was not until Papanicolaou’s collaboration with gynecologist

Herbert Traut (beginning in 1939), which led to the publication of

Diagnosis of Uterine Cancer by the Vaginal Smear (1943), that clinical

acceptance of the method began to develop. Their monograph documented

an impressive, irrefutable group of studies of both normal

and disease states that included nearly two hundred cases of cancer

of the uterus.

Soon, many other researchers began to confirm these findings;

by 1948, the newly named American Cancer Society noted that the

“Pap” smear seemed to be a very valuable tool for detecting vaginal

cancer. Wide acceptance of the Pap test followed, and, beginning

in 1947, hundreds of physicians from all over the world

flocked to Papanicolaou’s course on the subject. They learned his

smear/diagnosis techniques and disseminated them around the

world.

Impact

The Pap test has been cited by many physicians as being the most

significant and useful modern discovery in the field of cancer research.

One way of measuring its impact is the realization that the

test allows the identification of uterine cancer in the earliest stages,

long before other detection methods can be used. Moreover, because

of resultant early diagnosis, the disease can be cured in more

than 80 percent of all cases identified by the test. In addition, Pap

testing allows the identification of cancer of the uterine cervix so

early that its cure rate can be nearly 100 percent.

Papanicolaou extended the use of the smear technique from

examination of vaginal discharges to diagnosis of cancer in many

other organs from which scrapings, washings, and discharges

can be obtained. These tissues include the colon, the kidney, the

bladder, the prostate, the lung, the breast, and the sinuses. In

most cases, such examination of these tissues has made it possible

to diagnose cancer much sooner than is possible by using

other existing methods. As a result, the smear method has become

a basis of cancer control in national health programs throughout the

world