Jewish World Review Nov. 21, 2001 / 6 Kislev, 5762




Modified smallpox vaccine may reduce risk of cervical cancer

By Robert A. Wascher, M.D., F.A.C.S.

http://www.jewishworldreview.com -- CERVICAL cancer is the second most common cancer to specifically affect women, worldwide.

In the United States, it is the 7th most common female cancer, with nearly 16,000 cases diagnosed per year, resulting in 5,000 deaths per year. Cervical cancer is also one of the few human cancers known to be caused almost exclusively by a virus.

The human papilloma virus (HPV) is sexually transmitted, but causes no symptoms in the majority of men or women, although genital warts may sometimes arise following HPV infection. HPV infection of the genital tract is estimated to be present in 70-80% of sexually active women, although not all strains of HPV are thought to cause the changes in the cells of the cervix that can lead to cancer formation. Risk factors for cervical cancer include early age of first intercourse, number of sexual partners, genital warts, and smoking.

In an effort to prevent and treat cervical cancer, a British research team has modified the vaccinia virus previously used to vaccinate against smallpox. Using sophisticated gene manipulation techniques, the team grafted genes from HPV into the DNA of the vaccinia virus. This modified vaccinia virus then produces HPV proteins that can stimulate the immune system. Once stimulated, the immune system may then become more effective in eradicating HPV virus from the cervix of women with precancerous or cancerous cervical lesions.

This modified viral vaccine is currently being evaluated in a new study of women with precancerous changes in the cervix at the University of Wales. This new study is based upon the promising results seen in a previous trial vaccine study involving 29 women with advanced cervical cancer, and upon earlier studies in which the modified vaccine appeared to prevent tumor formation in female mice subsequently infected with cancer-causing strains of HPV. Unlike many previous gene therapy studies using living virus particles as the gene "delivery vehicle," the vaccinia virus used in this new study has a long record of safety as a "live virus" vaccine in humans. This represents an exciting approach to treating-and possibly preventing-a cancer known to be caused almost exclusively by viral infection.

NEW APPROACH TO BREAST CANCER DIAGNOSIS

The Journal of the National Cancer Institute recently reported on the results of a multicenter study of breast ductal lavage in patients known to be at high risk for developing breast cancer. Using tiny catheters, the researchers were able to inject saline solution into the nipple ducts that lead to the milk glands in the breast.

This fluid is then sucked back out of the duct, and analyzed by a pathologist for the presence of abnormal cells. All 507 women included in the study had normal breast exams and mammograms, but were deemed to be at increased risk of developing breast cancer based upon a prior personal or family history of breast cancer.

Atypical (precancerous) cells were found in 24% of the women studied by ductal lavage, or about 3-4 times more abnormal cells found by the earlier use of the more simple nipple aspiration technique. This is not surprising, as ductal lavage resulted in the collection of a median of 13,500 epithelial cells per breast duct, while nipple aspiration collected only an average of 120 epithelial cells per breast.

The human breast has 12-20 ducts that open onto the surface of the nipple, and it is often not possible to place a catheter into every nipple duct. However, this technique does offer a new approach to screening women who are at particularly high risk of developing breast cancer. Under ideal conditions, the test could conceivably detect precancerous or cancerous cells within the breast before physical examination, mammography or ultrasound could detect such lesions. If identified early enough by ductal lavage, patients with microscopic evidence of abnormal breast duct cells could then be offered preventive treatment with tamoxifen or surgery. However, large scale studies of this new technique must first be performed, as the mere presence of atypical ductal cells is known to raise the risk of developing breast cancer, but does not inevitably lead to cancer in all cases. The relationship between the presence of these abnormal cells and breast cancer risk requires further study.

NEW NON-INVASIVE PRENATAL DIAGNOSTIC TEST FOR DOWN'S SYNDROME

Down's syndrome (DS) is the most common genetic cause of mental retardation. DS is also known as trisomy 21, because the condition is caused by the presence of an "extra" (third) chromosome 21, instead of the normal pair. In the United States, approximately 4,000 babies are born each year with DS, or about 1 in every 800-1,000 live births. The incidence of DS is known to rise in the babies in mothers who are older than 35, but can occur at any maternal age.

In addition to mental retardation, which tends to be moderate-to-severe, there are several other features of DS that can occur. These include heart and gastrointestinal tract defects, decreased resistance to infection, visual problems, obesity, spinal malformations, hearing loss, and speech difficulties, among others.

Presently, the most accurate method of diagnosing DS during pregnancy in high-risk women is to insert a needle through the mother's abdomen to aspirate a sample of the amniotic fluid (amniocentesis), or to remove a small piece of the gestational sac around the fetus, both of which are invasive and may cause the loss of the pregnancy. Noninvasive tests, including tests of the mother's blood and ultrasound studies of the fetal skull and neck, are relatively inaccurate and often require testing late into the pregnancy.

As reported in the Lancet, researchers at King's College Hospital Medical School, in London, and the Ohio State University studied 701 fetuses at 11-14 weeks of gestation, using ultrasound to assess for the presence or absence of the nasal bones.

This approach was based upon the frequent observation, in the 19th century, of nasal bone underdevelopment in babies with DS. This ultrasound study determined that the nasal bones were absent in 73% of the fetuses with DS, as compared to only 0.5% of fetuses without DS.

By adding the nasal bone ultrasound study to the standard non-invasive diagnostic techniques, the researchers significantly improved the accuracy of prenatal diagnosis to about 85%, and did so very early in the pregnancy. This represents a significant improvement in the ability to accurately diagnose DS during early pregnancy, and without causing increased health risks to the fetus or the mother. This new ultrasound study of nasal bone development is, therefore, likely to become a standard part of routine prenatal testing.

JWR contributor Dr. Robert A. Wascher is a senior research fellow in molecular & surgical oncology at the John Wayne Cancer Institute in Santa Monica, CA. Comment by clicking here.

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© 2001, Dr. Robert A. Wascher