Ovulation May Weaken Cervical Cancer Vaccine

Strength of immune reaction may fade during menstrual cycle

(HealthDay is the new name for HealthScoutNews.)

TUESDAY, Aug. 5, 2003 (HealthDayNews) -- Vaccines against the strain of human papillomaviruses implicated in half of cervical cancers may weaken dramatically around the time women ovulate.

Although such a falloff hasn't been directly demonstrated, a new study by Swiss and U.S. researchers has found the immune system's response to the vaccine waxes and wanes during the menstrual cycle. The response hits a low during ovulation, when it's as much as nine times weaker than at other times of the month.

The finding isn't cause for alarm, but it raises a question that two ongoing vaccine trials may want to address, says study co-author Dr. Douglas Lowy, a lab chief at the National Cancer Institute. "With these large-scale trials it should be possible to pose the question: Is there possibly a difference in vaccine efficacy for women who are taking [oral] contraceptives versus those who are ovulating."

Cervical cancer strikes nearly a half million women each year worldwide. The disease is the second leading cancer killer in women, claiming almost 300,000 lives annually. The vast majority of those are in the developing world, where access to early screening tests such as the Pap smear is limited.

Almost every case of cervical cancer in the United States and abroad is thought to result from infection with human papillomaviruses, or HPV, which also cause genital warts. One member of this family, HPV 16, is linked to about half of cervical tumors. Blocking infection with the virus should all but erase the risk of developing the cancer associated with the HPV 16 strain.

No cervical cancer vaccine has been approved for marketing in the United States. Two are now being developed, one by Merck & Co., the other by GlaxoSmithKline, and public health experts consider their impending arrival a major advance. Both rely on the same technology, using a single noninfectious protein identical in structure to the molecular backbone of HPV 16 to trigger an immune reaction.

Recent studies have shown both experimental vaccines to be highly effective. One, for example, produced immunity from HPV 16 in every woman who received it.

As the new research suggests, however, timing may play an important role in how well cervical cancer vaccines work. The scientists, who report their results in the Aug. 6 issue of the Journal of the National Cancer Institute, followed two small groups of immunized women. Seven were taking birth control pills and 11 were not, allowing them to have normal menstrual cycles with ovulation.

Tests for proteins, called antibodies, that help the immune system fight HPV 16 showed a strong reaction to the vaccine in fluid collected from the women's cervixes. "The antibodies are found at reasonable levels at the cervix, which is where you would expect them to be if the vaccine" were to be effective, says Lowy, who helped develop the inoculation.

The amount of these antibodies stayed constant in the women on birth control pills. But they varied widely in the other women, spiking as the uterus added cells, plummeting ninefold during ovulation, then climbing again in anticipation of the next period.

Antibodies in general fall around the time of ovulation, Lowy says -- perhaps to make the woman's reproductive tract more hospitable to sperm.

While the exact mechanism for the antibody drop isn't known, Dr. Ronald Alvarez, a cervical cancer expert at the University of Alabama, says the new study, if confirmed, could make a difference in how doctors administer the HPV vaccine.

"It's a piece of information that's important to know. It has to be verified, but it will have some practical significance in terms of when you immunize patients and whether they should be on birth control pills while they're getting."

More information

For more on cervical cancer, try the U.S. Centers for Disease Control and Prevention or the National Cancer Institute.

SOURCES: Douglas Lowy, M.D., chief, laboratory of clinical oncology, National Cancer Institute, Bethesda, Md.; Ronald D. Alvarez, M.D., professor, obstetrics and gynecology, University of Alabama, Birmingham; Aug. 6, 2003, Journal of the National Cancer Institute
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