Prognosis Improves in Cervical Cancer War

Cervical cancer is the second most common cancer among women worldwide, trailing only tumors of the breast. But if a growing coalition of researchers has its way, the insidious disease should fall out of the top 10 within the next two decades and could eventually drop completely off physicians’ radar screens.

Every year, cervical cancer strikes nearly half a million women around the world; about 200,000 women a year die of the disease. But the bottom line, public health authorities say, is that the vast majority of those deaths are unnecessary.

Cervical cancer is caused by a virus called human papilloma virus, or HPV. New technologies for detecting that virus have made it relatively easy to diagnose cervical cancer at its earliest stages, when the disease is virtually 100% curable.

These new tests, some of which can even be conducted by women themselves, could bring cervical cancer screening to large areas of the world where women now receive little or no gynecological care.

Perhaps even more important, researchers have recently begun testing vaccines against HPV that hold the promise of eliminating most cases of cervical cancer by preventing infection.

“Cervical cancer can be the good-news story in our battle against cancer,� said Dr. Omega Logan Silva, president-elect of the American Medical Women’s Assn. “This disease is preventable.�

The first inroad against cervical cancer occurred six decades ago when Dr. George Papanicolau developed the Pap smear, in which cells from the cervix are removed with a swab and examined under a microscope. Abnormal cells indicate the presence of either cancer or dysplasia, a precancerous condition that normally leads to cancer.

Dysplasic cells can be easily removed, preventing their progression to full-fledged cancer. If invasive cancer is detected, the five-year survival rate is less than 50%.

The conventional Pap smear is about 67% accurate, meaning that it misses as much as a third of all abnormalities. Newer versions, such as the ThinPrep technique, increase the accuracy to 75% to 80%.

More than 50 million Pap smears have been given in the United States over the last 45 years, and their use has slashed the incidence of cervical cancer by 75%. This year, the American Cancer Society predicts, 4,800 women will die of cervical cancer and 12,800 will be diagnosed as having the invasive form of the disease.

Many of those will die needlessly. Studies show that 60% or more of the women with invasive cancer had not had a Pap smear in the five years before diagnosis of their disease. In many of the other cases, the screening missed the abnormal cells.

A new test for HPV--a sexually transmitted virus that causes genital warts--could sharply reduce the number of undetected cases. Its use is based on the recent recognition that the vast majority of cervical cancers--perhaps as many as 93%--are caused by HPV. Genetic susceptibility is important and smoking also plays a role, but most women simply will not develop cervical cancer unless they have an active HPV infection.

That doesn’t mean that everyone who is infected by the virus will get cancer. In fact, most women don’t. About 40 million American women have been infected with HPV. But there are at least 70 different strains of the virus and only 13 of them have been linked to cancer. Those 13 together account for only about 1% of all infections.

DiGene Corp. of Beltsville, Md., has developed a test that looks for DNA from those 13 cancer-causing viruses in cell samples taken from the cervix. The test has been approved in the United States as an adjunct to the Pap smear.

The test is most often used now in women who have an abnormal Pap test in which technicians find so-called atypical squamous cells of undetermined significance, or ASCUS.

ASCUS cells are not normal, but they are not clearly precancerous either. Physicians normally wait six months and give a follow-up Pap test to look for changes in the cells--an agonizing period during which the woman often wrestles with fears of cancer.

But a large study by Kaiser Permanente released last May showed that HPV testing can eliminate much of that fear. Dr. M. Michele Manos and her colleagues found that if the ASCUS cells were not infected by HPV, there was little chance of their becoming malignant and no need for immediate follow-up testing. A positive test indicated that further care was necessary.

The HPV test also can be used for primary screening. Last week, two studies in the Journal of the American Medical Assn. explored its use in two high-risk populations that had not previously undergone screening--one in South Africa and one in Costa Rica.

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The teams reported that HPV testing of samples collected by technicians was more sensitive in detecting cancer and dysplasia than conventional Pap smears. In both studies, the HPV test detected 85% to 90% of cancers or dysplasias, compared to less than 70% for the conventional Pap smear. The South African study also examined women who collected their own tissue samples at home using a cotton swab. In that case, the HPV was at least as accurate as the Pap test.

False positive tests--in which the presence of HPV was shown, but no cancerous cells--were more of a problem with HPV testing than with Pap smears. They were most common in women under 35.

Many of these women probably had a transient HPV infection that was subsequently cleared by their immune systems, said Dr. Thomas C. Wright Jr. of Columbia University, who led the Capetown study. Such women should be watched carefully in the future, he added, because they have an increased risk of cancer.

But when the virus is present in a woman over 40, he said, it indicates the presence of a persistent infection and is almost always linked to cancer or dysplasia. “I think for women over age 35 to 40, HPV testing will end up, in the near future, replacing a regular Pap smear,� Wright said.

Given that HPV causes cervical cancer, the next obvious step is to prevent infections by using a vaccine. Several groups have already developed prototype vaccines using genetically engineered proteins from the viral surface in an attempt to stimulate immunity.

One such vaccine, developed by Merck Research Laboratories, contains proteins from four human papilloma viruses that account for as much as 85% of all cancer-causing infections.

A team headed by Dr. Daron Ferris of the Medical College of Georgia recently began clinical trials to test the effectiveness of the vaccine. As is true with all vaccine testing, however, it will be years--perhaps a decade or longer--before researchers can determine whether the HPV vaccine really works. SmithKlineBeecham also has developed an HPV vaccine, and trials of a third vaccine are underway in England.

“If the vaccine is successful, then we would want to vaccinate the population, and that would include vaccinating school-age children at approximately 12 years of age, before individuals become sexually active,� Ferris said.

For more information about cervical cancer and HPV testing, visit:

https://www.cervicalcancercampaign.org

https://www.nccc-online.org

and https://www.digene.com.

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HPV and Cervical Cancer

Screening for infection by the human papilloma virus, or HPV, is a more effective way of detecting cervical cancer than the conventional Pap smear. As many as 93% of cervical cancers are caused by HPV.

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Sources: Digene Corp., Mayo Foundation for Mecial Education and Research

Researched by Times medical writer THOMAS H. MAUGH II