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For other articles and previous issues click here. April 19, 2004 The
HPV Connection Prepare to change the way you think about human papillomavirus (HPV). Generally associated with genital warts and thought of as a “dirty” sexually transmitted virus, HPV isn’t something most people want to hear they have. However, chances are high that sexually active people will contract the virus at some point in their lives. But, what many people don’t realize is that there is more to HPV than just warts and a stigma. It has been found to be the sole cause of cervical cancer. New developments in the detection of HPV could change not only the incidence of cervical cancer, but also the way women think about their healthcare. HPV: The Root of the Problem Although cervical cancer is not as common as it once was, there is still cause for concern because HPV is the most common sexually transmitted virus in the United States. “There are more than 100 different strains of HPV, 35 of which can infect the genital tract. Approximately 80% of all sexually active men and women have been or will be infected with one of them in their lives,” Savard says. She adds that because only a few of the genital strains of HPV cause warts and the rest are asymptomatic, many men and women don’t ever know they harbor the virus—a potentially dangerous fact for women since the high-risk strains of HPV responsible for cervical cancer are included in this asymptomatic group. However, Savard says, most of the time, these symptomless HPVs are transient, meaning they will go away on their own. This is true even for the strains of HPV most commonly found in cervical cancer. “In most cases, men’s immune systems will slough it off fairly quickly, and the majority of women’s do the same after one or two years. It is extremely common for someone to have had the virus and not ever know it,” she explains. This could be why HPV has become such a common disease, says Rodney H. Smith, MD, of the Arizona Wellness Center for Women. “It’s true that in 80% to 90% of cases, HPV will take care of itself,” he says. “It’s a very easy problem to control, which is probably why we’ve seen such a big rise in it. We’ve made it just a nuisance disease.” He continues: “In the same way our bodies never get rid of the chicken pox virus, HPV will always be in our systems once we contract it. But, chances are that it will never flare up and become a problem again unless the immune system is compromised. The body naturally keeps it in check.” So, does testing positive for HPV equal cervical cancer? Almost never, says Tom Cox, MD, director of the gynecology clinic at the University of California at Santa Barbara. “A positive test for HPV just means that you need to be rechecked in six to 12 months to see if the virus has gone away. Only if you test positive again would there be a need for further checkup to see if there are changes in the cervix that may need to be treated so that cervical cancer could not occur,” he explains. “Just because a female tests positive for HPV does not mean that she certainly has or will get cervical cancer,” Savard adds. “We’ve got to destigmatize HPV—it’s important to remember that this virus is extremely common but cervical cancer is not.” Of the roughly 100 strains of HPV, there are approximately 20 that have been associated with cervical cancer.1 But, Savard says, there are two that account for a majority. “Strain No. 16 causes about one-half of all cases, and strain No. 18 is responsible for 20% to 25%,” she says. “Again, these are not the types that appear as warts—these are asymptomatic.” It is unknown at this time what causes HPV to trigger the cancer formation, but Smith says several theories abound. “The virus gets in the nucleus of the cervix cells and hijacks the cells’ reproductive mechanisms, thus spreading,” he explains. “We don’t know right now what exactly starts the malignancies to grow.” Setting the Standard: The
Pap Test According to the Penn State College of Medicine, a Pap test is performed by “scraping cells from the surface and inside of the cervix. These cells are then smeared onto glass slides, sprayed with a preservative to protect the cells, and then sent to a laboratory for examination under a microscope.”2 “There’s no denying the importance of the Pap test,” says Cox. “Since it’s introduction, Pap tests have eliminated 75% of cervical cancer deaths in the United States. It was the second most common cancer in women in the late 1940s and the second most common cause of death. Now, it’s No. 11 in incidence and No. 13 in mortality in the United States.” Savard adds that in addition to cervical cancer prevention, Pap tests have also become synonymous with female healthcare. “For so long, women’s health has been defined by the Pap test,” she says. “I used to tell my female cardiac patients that women thought as long as they had their Pap tests, they’d be OK.” As most women know, gynecological exams and other preventative health exams are recommended annually. What many women might not know is that the recommendations of when to start getting Pap tests and how often to get them has changed within the last few years. According to the U.S. Preventive Health Services Task Force and the American Cancer Society, it is now recommended that Pap testing begins three years after first intercourse or at the age of 21, whichever comes first.3 “This is different from the original recommendations that Pap testing begin at age 18 no matter what,” says Savard. “Since chances of getting HPV increase with the number of sexual partners you have and the age at which you first have intercourse, it’s important to begin testing according to these new guidelines.” Cox says that Pap tests, while in most cases effective in early detection of cell changes before they become cervical cancer, do not screen for HPV. “Pap tests are different from HPV detection tests because Paps are only looking at cell changes,” he explains. “Some cell changes that appear may be due to inflammation caused by tampon use, yeast infections, etc. Also, the cell changes on a Pap are often very difficult to read, and cytopathologists often disagree on what is seen. The Pap test is very subjective in that respect.” Savard believes that these inconsistencies can add up. “Approximately 40% of all cervical cancer patients had been screened with Pap tests—meaning the test was not effective in catching the cell abnormalities,” she says. Taking Out HPV The DNAwithPap test is different from a regular Pap test in several ways. “Whereas a Pap test looks at cells through a microscope, an HPV screen looks in the cells’ DNA for a panel of high-risk viruses—all types that have been found in cervical cancer,” explains Cox. “A woman who tests positive on a single HPV test but has a normal Pap reading is most likely to clear the virus on her own. Women who test positive again for HPV will still most likely not have cells that would lead to cancer if not treated, and cancer already present would be very rare, but further evaluation will be important. “In contrast, women who test positive for HPV and have an abnormal Pap test should be evaluated as soon as possible,” continues Cox. “Almost no disease is missed if both the Pap test and the HPV screen come back negative.” Smith says that one part of the approval expected to bring about confusion is the over-30 stipulation. Why 30? “The longer you have HPV, the higher your chances of cervical cancer are,” explains Smith. “The problem is that we can’t yet predict whose viruses are going to develop into cancer, so we’re making the assumption that women over 30 who test positive for HPV are a more high-risk population.” Cox adds, “The problem is that most women under 30 will test positive for HPV—in fact, one in four will be positive at any one time and up to 80% would likely be positive at least once if tested frequently over time. In most of those cases it will be transient. HPV testing of women under 30 would lead to too many positive results; too much worrying over something that almost always goes away on its own.” Savard says that while she agrees with the over-30 stipulation, she believes that it’s important to spread the word about HPV to women of all ages. “Many OB/GYNs don’t tell their patients that they have HPV because they don’t want to scare them,” she says. “But women are smart, and they want information. It all comes down to education. Maybe if more women knew about the connection between HPV and cervical cancer, it would make them take more responsibility for their health.” What This Means for Women’s
Healthcare Women testing negative on both Pap and HPV tests have an extremely low risk of having cervical cancer in the three years following the test, so increasing the screening interval should not increase risk, says Cox. “Even if you contracted the highest-risk HPV the day after your test came back negative, you would not get cervical cancer within the three years before your next screening,” he says. “There’s about a five- to eight-year window at the very minimum between getting the virus and developing cervical cancer. This may provide more leeway to those women who might not be consistent about their checkups.” Cox and Smith say the “waste of money” Savard mentioned is a large factor in the addition of the HPV test. “I believe that this approach should be more cost-effective if it reduces the risk of women having as many false-positives from misclassified Paps as they presently have when Pap tests are done annually,” says Cox. “It saves healthcare dollars,” agrees Smith. “HPV testing won’t save lives—it will just help us identify the women we do and don’t need to pay further attention to. This is not going to make us any less likely to get cervical cancer, but it will tell us who we need to treat more aggressively.” Savard takes a different viewpoint, saying that the DNAwithPap test approval is going to have an immense impact on women’s health. “This is a truly exciting progression because it means that we will most likely see cervical cancer completely eliminated in our lifetimes,” she says. But Smith is more hesitant about the impact it will have. “When we make an assumption based on studies, like with the DNAwithPap test, the real test is what happens in real life,” he says. “We’ll get an opportunity to see if we’re right. The general public needs to realize that this is all a test, all speculation. There will definitely be changes along the way for further fine-tuning, but I think we’re on our way.” — Kara McDonald is an editorial assistant
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