By Lori Tighe
HPV test may alleviate undue worry for the 5 to 7% of U.S. women who receive abnormal Paps annually
To be an American woman with healthcare insurance is to receive an annual Pap smear test. This collective ritual and its associated treatment costs the United States $6 billion annually, making us among the few countries to spend that much on a test to prevent cervical cancer. After breast cancer, cervical cancer ranks second worldwide as the most common cancer in women. About 12,900 cases of cervical cancer are found in the United States annually; 4,400 die from it each year. In comparison, the world has an estimated 400,000 cases annually, which kill 200,000 a year, mostly in developing countries where women can’t afford the $25 Pap test. The United States has traded dollars for deaths.
Although it has done wonders at reducing deaths, the Pap test has a flaw that has perplexed gynecologists and filled women with anxiety for decades. Of the 50 million U.S. Paps performed each year, about 5 to 7 percent, or 2.5 million come back abnormal or ASCUS (Atypical Squamous Cells of Undetermined Significance). They may be pre-cancerous, or they may be nothing. Doctors either direct their patients to a colposcopy, or take a wait-and-see approach and repeat the Pap, since cervical cancer usually takes 10 to 15 years to develop. Only 25 percent of these cases turn out to be precancerous or cancerous, thus many women needlessly undergo colposcopies, or “wait and worry” for nothing. On average, the follow-up treatment costs between $300 to $1,200 per woman.
Generating cost and anxiety
“This generates cost and anxiety. Working up those people has become problematic. It’s one of the most laborious things done in medical practice today, following these Paps up,” said Mark Schiffman, M.D., co-author of ALTS, or the ASCUS/LSIL (Low-grade Squamus Intraepithelial Lesion) Triage Study, done by the National Cancer Institute.
The ongoing ALTS study recently released the most conclusive results yet that a test for HPV, or human papillomavirus, may be the answer for abnormal Paps. In 1999, researchers determined that 13 among 100 types of HPV are found in 99.7 percent of all cervical cancer cases. While the ThinPrep Pap Test is 85 percent sensitive in finding cancers and precancers, an HPV test detects the virus that causes the disease and is 96 percent sensitive in detecting cervical disease. Not only is the HPV test more accurate, it can deliver the news before cells take a turn for the worse.
An NIH study of 3,500 women with ASCUS Pap tests showed that women who tested HPV- infection-free had a 99.5 percent probability of being healthy. It also meant that 45 percent of women studied who were HPV-negative safely avoided a colposcopy and possible biopsy.
Digene Corp. of Gaithersburg, Md., has the only HPV test on the market. Its Hybrid Capture 2 HPV DNA Test uses DNA molecular technology to detect HPV before visible cell changes occur. The Food and Drug Administration (FDA) approved the test in 1999 for U.S. use following an abnormal Pap smear result. The HPV test also is being marketed in select countries as a primary cervical screen, either in conjunction with or separate from the Pap smear.
HPV test to replace Pap?
In October, the company applied to the FDA for its HPV test to be used as a primary screening test in conjunction with the Pap. The company hopes for approval by the second half of 2002, paving the way for the HPV test to possibly replace the Pap as the first line of defense.
“Science suggests you don’t need constant screening for low-risk women,” said Chuck Fleischman, Digene’s president. Using the HPV test with the Pap as primary screening, “you can create a cost-effective, diagnostic method. We believe the use of the HPV test could save the U.S. $1 billion a year.”
The Netherlands is already talking about a woman having only three to four HPV/Pap screenings per lifetime, with better results than with the Pap alone. Yet U.S. doctors prefer to take a wait-and-see approach about curtailing the American woman’s annual Pap ritual.
“Pap smears have been such a gold standard,” said Mark DeFrancesco, M.D., chief medical officer at Women’s Health of Connecticut. “It takes an awful lot of time to change the way we’ve done things for 50 years.”
DeFrancesco uses the HPV test as a follow up to an abnormal Pap test now, and he favors its continued use. “All the evidence I’ve seen shows it’s highly effective and is a very good test. Will it replace the Pap, yes it could. But it remains to be seen.”
About 25 percent of inconclusive Pap patients in the United States now get the HPV test, but should more? Should it one day replace the Pap smear entirely? “It’s hard to say,” said Joanne Grosshans, program manager of the HPV Resource Center of the American Social Health Association. “The Pap is what women are used to receiving and what providers are used to giving. It would require revamping the entire process.” What is needed is more public education on sexually transmitted diseases, because HPV is so common, Grosshans said. An estimated 40 million Americans have HPV, yet a Digene study showed that only 20 percent of women knew that HPV causes cervical cancer.
The HPV test is gathered by swabbing the cervix just like a Pap smear. In fact, the sample can be collected at the time of a Pap smear. The specimen is placed in liquid and sent to a lab. The Digene HPV test uses molecular technology to detect the DNA of high-risk HPV in cervical cells.
When using the ThinPrep Pap Test clinicians can run Digene’s HPV test using the same patient sample, eliminating the need for a return physician visit or collection of a second sample. Most lab results come within one week.
“It’s a very important test,” Grosshans said. “It’s a matter of using it appropriately and dealing with issues associated with the stigma of a sexually transmitted disease.”
Lori Tighe is a freelance writer in Timonium, Md
