Milestones in the Development of Early DiagnosisCHAPTER 1

At the turn of the 20th century, two surgeons played a crucial role in offering a cure if cervical cancer was diagnosed in stage I or early in stage II. They were F. Schauta and Ernest Wertheim, Wertheim (Fig. 1.1) was assistant to Schauta at Prague. Both worked on cancer cervix. Schauta was invited to Vienna in 1891 to head the department of gynaecology. He took Wertheim with him. Schauta believed in Vaginal Radical Surgery. Later on in 1998 Wertheim went on to describe Abdominal Radical Surgery. Wertheim took the world by storm performing 1300 operations and did not loose one single case to follow up. He studied 40,000 serial sections of operated specimen. But mortality was high because of non availability of good anesthesia, antibiotics, blood transfusion etc. Nevertheless even now, after hundred years it is still regarded as a classic operation.

However when Wertheim went to Paris to present his paper on his surgery he heard of the results of Radium just introduced by Pierre and Marie Curie. He withdrew his paper saying “there is no place for radical surgery when non invasive treatment is available”.

We have to thank Marie Curie (Fig. 1.2) for her pathbreaking discovery of Radium. Marie Sklodowska Curie was born in Warsaw on 7th November 1867 and was an exceptionally bright student. Then women could not enter college in Poland so she went to Paris to do graduate studies. Poland's loss was France's gain. There she met and married Physicist Pierre Curie in 1895. The first radioisotope that Marie isolated was named Polonium after her country, Poland. Later they isolated radium.

The Curie family won four Nobel prizes. Marie and Pierre won the Nobel for the discovery of Radium in 1903. By 1911 Pierre was no more. Marie alone won again for work done by herself. In 1936 their daughter Irene Curie won a Nobel prize as she continued their work. Unfortunately, Marie did not live long enough to see her daughter winning the Noble prize. She died in 1934 of leukemia caused by prolonged exposure to radiation. The world then realized that radiation was not the only answer to treatment of cancer. It was hazardous too.

So once again attention was focussed on early diagnosis. Till this time cases were taken from stage I for treatment. So people wondered what came before stage I. The work of several people lead to the concept of precancer.

Kermawner said that there was an area of preinvasion surrounding invasive cancer. They thought that this is how invasive cancer spread. But it was Schiller in 1926 who said that this is how it begins. Walter Schiller is better known for his Schiller Iodine test. He ultimately left Germany post war and settled in USA. Maximum work on this was done by Telinde and Novak at Johns Hopkins University.

From 1929–34, Pemberton and Smith started reporting these cases as Carcinoma in situ. 1959 Hemperl from Bonn introduced the concept of microinvasion.

But the greatest contribution to the story of Preinvasive Cancer Cervix came from George Papanicolaou.

All these great men have left their footprints on the history of pre and early cancers.

Dr. Papanicolaou (Figs 1.3 and 1.4) is considered the father of cytology. He was born in Kymi in Greece in 1883. He completed his PhD from Germany and in 1913 migrated to USA and worked in Cornell Medical School in the department of anatomy. He did fundamental work in the discovery of ovarian hormones and their effect on vaginal cells. It was while studying vaginal smears at the Women's Hospital, New York that Dr. Papanicolaou saw tumour cells in smears from women with asymptomatic cervical cancer. “The first observation of cancer cells in a smear was the most thrilling experience of my scientific career.” he wrote. He communicated this discovery to the medical world in 1928 but unfortunately it did not arouse any enthusiasm in others. So he left the subject for ten years. It was only in 1941 that he published his work again in American Journal of Obstetrics and Gynaecology with Dr. Herbert Traut. They also presented a monograph titled ‘Diagnosis of Uterine Cancer by Vaginal Smears’ in 1943. Now it was widely accepted as the climate of opinion was very different. The concept of carcinoma-in-situ was more widely accepted. Gynaecologist felt the conquest of cervical cancer was in sight. Papanicolaou finally received the acclaim he deserved. Screening was initiated in Massachusetts in 1945. Cytology progressed well and Pap smear became a routine. Mortality due to cancer cervix which was 14 per 100,000 women in 1940 came down to 4 per 100,000 by 2000. Many screening programmes were started all over the world.

The American Cancer Society sponsored a national cytology conference in Boston in 1948 and about the same time a regular training course in cytology was instituted at the New York Cornell Medical Centre. His wife Mary played an equally important role in developing cytology. After his death in 1962, she continued his work at Papanicolaou cancer research centre in Miami which was set up by them. The American Cancer Society honored her with a plaque “Companion to Greatness”.

In 1924, Hinselmann (Fig. 1.5) was working in Bonn under Professor Von Franque. At that time it was believed that cancer started as a pin point spot and Hinselmann set out to discover a method that would identify this spot.

Like many innovators in history, Hinselmann was not taken seriously by his contemporaries, in the beginning. Once he moved to Hamburg few years later, things seemed to improve, but only temporarily. Then came the second world war with all its calamities. Hinselmann lost his two eldest sons in the war. In the post-war period a jury of British generals sentenced him to three years imprisonment because six gypsy women had been sterilized in his service by his assistants. The sentence was later reduced to half for health reasons. With all these setbacks, colposcopy was forgotten for many years in Germany, but continued to prosper in South America under Hinselmann's students Rieper and Jakob.

Having recovered from the war and imprisonment, Hinselmann decided to restart his work in 1949, at the age of 65. By the time the great success of Papanicolaou's smear test distracted attention from colposcopy. Nevertheless, Hinselmann proved that all modalities if used correctly were necessary to perfect early diagnosis and prevent invasive cancer. His famous words were “Those who believe cytology is superior to colposcopy know nothing of either.”

In 1949, Hinselmann migrated to Brazil where he was treated with due honour. To quote his own words “They gave me back my honour, and made me feel like a human being again.”

Hinselmann made several trips all over the world lecturing and demonstrating his skills. In 1957 he was granted the title of Doctor Honoris Causa by the University of Brazil. With increasing International communication, colposcopy underwent an enthusiastic revival outside Europe, especially in the United States. The ability to obtain a biopsy specimen from the correct site and reduce the number of conization was responsible for the eventual acceptance of colposcopy.

Another radical change in thinking was introduced in 1970 by Zur Hausen, who said that a Papilloma virus infection was a major cause of Invasive cervical cancer. Much research was done in virology to detect the causative viruses. HPV DNA testing was introduced in clinical practice. Primary screening for HPV DNA testing is done in several countries. It decreases the load on pap smear screening and it can be done in conjunction with pap smear. Currently HPV DNA testing is an expensive test. However much research is going on to make it simple, inexpensive and quick so that it can be used for mass screening.

Dr Wahi pursued a post graduate career in Pathology and completed his M.D. in 1934. He then went to U.K. to do the MRCP which he completed in 1938.

It was during Dr. Wahi's tenure at the S. N. Medical College, Agra, that he worked tirelessly on the subjects of oral and cervical cancer. His experimental work on swiss albino mice established beyond doubt the fundamental understanding of the natural history of the disease. It was published in Acta Cytologica.

He trained a large number of students who later developed centres of cytology at Chandigarh, Delhi, Lucknow and Pondicherry and Mumbai.

Dr. Wahi was the recipient of several awards including the Padma Bhushan. He had more than 300 publications in both National and International journals. He was the founder member and first President of the Indian Academy of Cytologists.

By 1960, Hannah Peters had left Bombay but two centres of cytology had developed by then. One was the Contraceptive Testing Unit at Indian Council of Medical Research where all women who were accepting contraceptive had cytology and colposcopy performed on them.

The second was the cytology laboratory of Tata Cancer Hospital. This cytology laboratory was started by the Indian Cancer Society in 1976. It was later amalgamated with the hospital. It is accredited by the International Academy of Cytology.

In 1967 the Association of Medical Women in India celebrated its diamond jubilee. At this time funds were collected which were used to start a cytology clinic at the Cama and Albless Hospital. The superintendent of Cama and Albless Hospital at that time was Dr. Segulla Aptekar, who spearheaded the project and put Dr. Usha Saraiya in charge of it. The clinic was oriented to teaching and research in addition to patient service. Screening was performed for mainly Cama and Albless Hospital patients and also patients from private clinics and rural camps.

In 1976 a special Dysplasia clinic was started where cases with abnormal findings were studied by colposcopy and a long-term study carried out.

In 1984 when the State Cancer Control Programme “was launched, detection centers were started all over Maharashtra, especially at district hospital. An innovative approach of conducting cancer detection camps in urban and rural arrears was greatly successful and spread the message of early detection.

We have come a long way in the last 100 years or so; with the 20^th century having contributed significantly to the history. However the sun has yet to set on the invasive cancer cervix. 21^st century promises to be very eventful with further research in immunology, virology and molecular biology. The recent introduction of vaccines promises to make the goal of control feasible. There is finally some hope that the sun may finally set on Invasive cervical cancer.

The emphasis is more now control of cancer rather than a cure of cancer. The emphasis has also shifted to the control in developing countries where incidence is still high and health infrastructure poor. Emphasis has also to be focused on Public Education and Women's Empowerment. Women have to understand the need to take care of their health and come forward for regular check-ups.