Friday, November 28, 2008

Neoplasms: Excerpt 10

Here is another short excerpt from my recently published book, Neoplasms: Principles of Development and Diversity.

"Many more people are alive today as the result of precancer treatment than are alive due to the treatment of cancers.

The successful reduction in deaths from cervical cancer provides a good example of the effectiveness of precancer treatment. Cervical cancer is a type of squamous cell carcinoma that develops at the junction between the ectocervix (the squamous lined epithelium) and the endocervix (the glandular lined epithelium) in the os of the uterine cervix of women. Before the introduction of cervical precancer treatment, cervical carcinoma was one of the leading causes of cancer deaths in women. Today, in many countries that have not deployed precancer treatment, cervical cancer is the leading cause of cancer deaths in women (72, 73). The relatively low number of cervical cancer deaths in the United States is the result of a 70% reduction in age-adjusted mortality after the introduction of Pap smear screening (74–76). No effort aimed at treating invasive cancers has provided an equivalent reduction in the number of cancer deaths as this simple procedure for treating precancers.

Today, we know that almost all cervical cancer is due to infection by one of several carcinogenic strains of human papillomavirus. The strains of human papillomavirus that cause cervical cancer are transmitted during sexual intercourse by men infected with the virus. In the late 1940s (and really up until the early 1980s), the viral etiology of cervical cancer was unknown. We did know that morphologic changes in cervical epithelial characterized the early steps in cervical cancer development. By sampling and examining cervical specimens from women, it was possible to accurately determine whether precancerous changes were present. If precancerous changes were present, a gynecologist could remove a superficial portion of the affected epithelium, and this would, in the vast majority of cases, stop the cancer from ever developing.

Thanks largely to the persistence of Dr. Papanicolaou and his coworkers, a screening test was developed to detect cervical precancers. The Pap smear is obtained by scraping or brushing the junction between the endocervix and the ectocervix and
spreading the detached cells onto a glass slide. The cells are then stained with a histologic reagent (the Papanicolaou stain) that allows the cytologist to visualize subtle alterations in cell morphology. A typical Pap smear contains about 20,000 cells, and every cell must be inspected to rule out dysplasia and other pathologic abnormalities.

A large cytology laboratory can handle hundreds of thousands of Pap smears in a year. In the last half of the 20th century, the Pap smear cytologic evaluation led to at least a 70% drop in the number of deaths from cervical cancer in every country that fully deployed the test.

Morphologic and epidemiologic observations on Pap smears provided clues that led to the identification of several strains of human papillomavirus as the major causes of cervical cancer. [Half of the The 2008 Nobel Prize in Medicine went to Harald zur Hausen, for his work, showing the relationship between human papillomavirus and cervical cancer]. Recently, a vaccine against carcinogenic strains of HPV has been developed. Gardasil and Cervarix are two HPV vaccines that are currently available. If all goes well, most cases of cervical cancer will be prevented by a cancer vaccination. The Pap smear industry will shrink as fewer and fewer women test positive for cervical dysplasia.

The examination of Pap smears is just one of the many activities of a cytology laboratory. Cytologists routinely diagnose cells obtained from virtually any anatomic site and from any body fluid."

- Jules Berman


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