Long Duration in the Progression of Cancer
Cancer is a dreaded disease, all the more so since we are frequently exposed to images of it in its later stages -- after it has destroyed tissues and organs, caused failure of function, and eventually death. While the precise events in the progression of cancer are not yet known, what we do know now is that there is a long interval between the first event that initiates cancer and its full clinical manifestation.
The Process of Carcinogenesis
Research done on animals in the course of this century and numerous clinical observations have contributed to our present understanding of carcinogenesis, i.e. the process of the genesis of cancer. For instance, repeated application of coal tar on rabbits' ears produced cancers of the skin. The procedure first induced papillomas (benign tumours), followed by carcinomas (malignant tumours). Further research revealed that there were changes in the cells of the skin long before the papillomas appeared, and there was another long interval before carcinomas were produced.
Precancerous Changes
While cancer statistics record deaths and diagnoses, they seldom record the incidence of those who harbour cancer cells which may develop into cancer. It is in fact possible now to detect precancerous changes in the respiratory tract, the urinary tract, the gastrointestinal system, the oral cavity, and the female genital tract, thanks to the hard work of generations of medical researchers.
The Case of the Uterine Cervix
Of the various sites mentioned, the best understood is that of the cancer of the uterine cervix. In the late nineteenth century, precise diagnosis of the cancer became possible with the introduction of histopathology, i.e., what a pathologist can see from a biopsy. However, a biopsy involves discomfort for the patient, for an operation has to be performed to take living cells from the uterine cervix for purposes of study and diagnosis.
The next significant breakthrough came with the introduction of the Pap smear method which involves the use of exfoliative or abrasive cytological techniques. A smear of exfoliative cells (as opposed to living cells in a biopsy) from the uterine cervical lining is placed on a glass slide; the addition of some chemicals enables a study of the size, shape and colour of the cells, which can indicate whether the cells are cancerous. The method does away with the operative discomforts and the cost of taking biopsies while yielding the same accuracy. The changes as indicated by a Pap smear correlate well with what a pathologist can see from a biopsy of the cervix. This and the fact that it is a relatively easy test has resulted in its wide application for the screening and early diagnosis of cervical cancer, and has in many instances enabled a cure of the disease before it reaches the invasive stage.
The Case of the Human Nasopharynx
Histologically, the structure of the cells lining the human nasopharynx is curiously similar to that of the cervix. This prompted experts from the University to undertake research to find out if precancerous changes of the nasopharynx are similar to those of the cervix. The research team comprised Prof. Joseph C.K. Lee, Prof. Dolly W.S. Huang, Prof. Michael W.M. Suen and Mr. L.J. McGuire of the Anatomical and Cellular Pathology Department, Dr. H.G.S. Murray of the Microbiology Department, and Prof. C.A. van Hasselt of the Surgery Department. They were awarded a competitive grant of HK$ 620,000 by the Research Grants Council in 1989 to carry out their research.
Using tissue from over 300 biopsies taken from suspected nasopharyngeal carcinoma patients and from 200 human nasopharynxes removed at autopsies, they characterized and defined the changes involved in the development of nasopharyngeal carcinoma. Four different methods were employed.
First, the researchers conducted histological studies wherein tissues were fixed in formalin and embedded in paraffin. Very thin sections (0.005mm) were cut and stained and then viewed under the microscope. The diagnosis was based on colour change, intensity of staining, and the relationship between different tissue components. The appearance of cells, in terms of the amount of cytoplasm and size and shape of nuclei and nucleoli, was also observed.
Morphometric methods were then used to measure the size and distribution of cells in the epithelia of many sections of each specimen. The process was very time-consuming and tedious. In some cases, serial sections were taken to observe the relationship of one group of cells to another. After collecting an enormous amount of data, all information was subjected to statistical analysis to ascertain the effect of a large number of variables.
Researchers can use chemicals to react with specific substances in a cell or tissue to give a colour indicating the nature of a substance, a method called histochemistry. The CUHK team used immunohistochemistry in their research, in which colour reaction is extended further by exploiting the mechanism of antigen-antibody detection in tissues. Appropriate controls help the results to be specific and quantifiable, and the amplification achieved renders the method sensitive, which is why it is used extensively in research and diagnosis in pathology.
The researchers also used lectins (plant products that have specific affinity to carbohydrates on cell surfaces) to distinguish abnormal cells from normal cells. The carbohydrate components recognized by some lectins are not present in normal nasopharyngeal epithelium, but show variable changes when the cells become abnormal.
After in-depth and extensive studies, the researchers finally came to the conclusion that precancerous changes at both sites, i.e. the cervix and the nasopharynx, are highly similar. Corresponding to the three stages of precancerous change of the cervix CIN I, II, and III (CIN denoting the intraepithelial neoplasia of the cervix), the researchers defined those of the nasopharynx as NPIN I, II, and III.
| Precancerous Changes |
| Uterine Cervix | Nasopharynx |
 Hyperplasia |  Hyperplasia |
 Carinoma-in-situ |  Carinoma-in-situ |
 Carcinoma of Cervix Uteri |  Nasopharyngeal Carcinoma |
Direction of Further Related Research
These research efforts are now being furthered by other experts in the Anatomical and Cellular Pathology Department, who wish to ascertain whether a smear method can also be used to diagnose cancerous changes in the nasopharynx as easily and accurately as in the case of the uterine cervix. The road ahead could be arduous and long, bearing in mind the 50 years of hard work and experience that preceded the success of the Pap smear method.
We are now witnessing the development of automatic screening of Pap smears by machines, which can check human error or oversight in the diagnosis of cervical cancer. Spurred on by such progress, the research team headed by Prof. Joseph C.K. Lee hopes that, with more research and systematic collection of accurate data, cytological screening of nasopharyngeal carcinoma using exfoliative cytology can soon be a reality in Hong Kong. This would enable its early detection, and possibly cure, before it reaches the invasive stage.
