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Banishing Cervical Cancer

A new vaccine promises to prevent cervical cancer, but will its use be widespread?

By CARMEN MARTI

In 1973, researchers concluded that if a virus was found to cause cervical cancer, as was suspected, ?a vaccine cure can be developed.? Thirty-three years later, a vaccine has been developed; now we have the potential to almost completely eradicate cervical cancer, the second biggest cancer killer of women around the world.

?We are at the stage of vaccines,? says Dr. Bobbie Gostout, associate professor of gynecologic surgery at Mayo Clinic and communications chair for the Gynecologic Cancer Foundation. ?We have vaccines to fight measles and vaccines to fight polio. A vaccine to prevent a deadly cancer? That?s huge. This is such good news.?

By the early 1980s, scientists had identified human papillomavirus (HPV), a sexually transmitted disease, as the cause of cervical cancer. The National Cancer Institute went to work and found a way to prompt the immune system to fight the virus. From there, pharmaceutical companies began to develop vaccines.

Two companies are currently on the verge of gaining approval for cervical cancer vaccines. In the United States, Merck & Co. announced in February that its vaccine, Gardasil, was given priority review by the

U. S. Food and Drug Administration. This means approval could be gained here as early as June. Merck has also submitted applications to regulatory agencies in the European Union, Australia, Mexico, Brazil, Argentina, Taiwan and Singapore and has launched a collaboration to study the vaccine in developing populations in India.

In Great Britain, GlaxoSmithKline (GSK) announced it would seek regulatory approval for its experimental vaccine, Cervarix, in Europe and countries outside the United States in 2006.

Both vaccines have been shown to be 100 percent effective in protecting women against two strains of HPV, types 16 and 18, which are linked to more than 70 percent of all cases of cervical cancer. Gardasil has also been shown to prevent types 6 and 11, which account for an estimated 90 percent of genital wart cases. There are more than 100 types of human papillomaviruses. Certain types cause benign papillomas or warts; others are linked to genital cancers, including cancers of the cervix, vulva, vagina, anus and penis. HPV is so prevalent -- approximately 20 million American men and women are currently infected -- physicians say nearly everyone who has had sexual intercourse has been exposed. Ninety percent of women have carried HPV. In most cases, HPV goes away on its own; in others, if undetected, it causes cancer.?

Therefore, a vaccine that prevents human papillomavirus is effectively a vaccine to prevent cervical cancer, since a dozen types of HPV have been identified in 99 percent of cervical cancer biopsy specimens worldwide. If HPV can?t establish itself, neither can the cancer.

These vaccines, Gostout says, which are effective in both females and males, ?are beyond everyone?s wildest expectations.? Even if they don?t live up to the 100 percent effectiveness the clinical trials are producing, ?it doesn?t matter,? she says. ?You have to temper 100 percent with the knowledge that the vaccine will be so widely used it probably won?t be 100 percent effective. But 96, 97, 98 percent will lead to everyone being protected.?

Gostout says at that point a phenomenon called ?herd immunity? kicks in. ?When most are protected,? she explains, ?everyone else is too because the bug isn?t being passed around. The effectiveness rate may not be exactly 100 percent, but it?s ultimately 100 percent.?

This is particularly good news in the United States and other developed countries, where access to health care and attention to reproductive health have become relatively commonplace over the past 20 years. While half-a-million cases of cervical cancer are diagnosed worldwide, leading to approximately 300,000 deaths each year, only about 10,000 new cases of cervical cancer were diagnosed in the United States in 2005, with approximately 3,700 deaths. Around the world, cervical cancer is the second deadliest cancer for women; in the United States, it has been taken off the Top 10 list of cancer deaths for women, thanks to ?the miracle of Pap smear screening,? Gostout says. ?That means something, but it doesn?t mean we?ve won the battle.?

Even in the United States, neighborhoods where the poverty rate is 20 percent or higher are associated with lower rates of cervical cancer screenings, according to a Harvard University study published this winter in CANCER. It found that black women living in poor communities are less likely to be current with cervical cancer screening than those living in wealthier areas.

This is consistent with a National Cancer Institute report last summer that concluded ?the nation?s public health system must improve its delivery of cervical cancer education, screening and treatment and related health care to women at risk.? The researchers noted that ?despite a consistent decline in cervical cancer deaths in the United States overall, patterns of high cervical cancer mortality have existed for decades in specific geographic areas and populations. Those groups with the highest mortality rates include African-American women in the South, Hispanic women along the Texas-Mexico border, white women in Appalachia, American Indians of the Northern Plains, Vietnamese-American women and Alaska Natives.?

But lack of access to health care isn?t the only reason many women in the United States don?t get regular Pap tests. Gostout says complacency also plays a role. Women in the age group when cervical cancer usually develops -- those in their 30s, 40s and 50s -- are often at one of the busiest times of their lives. They juggle childrearing, careers and other responsibilities, sometimes overlooking their own health needs.

Others don?t realize they are at risk, believing a monogamous relationship is preventative, but promiscuous sex isn?t the only way to contract HPV. ?Couples considered to have a healthy sex life are at risk, too,? Gostout says. ?Even single lifetime partners have a 10 percent risk of HPV. This virus is so pervasive it?s hard to avoid getting it.?

Gostout adds that a third reason cervical cancer persists in the United States, is ?Paps aren?t perfect. We don?t have it all under control,? she says. ?There?s work to do in this country.?

Some of that work should include intensifying outreach to women who have rarely or never been screened for cervical, breast or colon cancer and other screenable diseases, the National Cancer Institute study said. Materials need to be developed that are linguistically and culturally appropriate, and strategies to remove cultural and economic barriers to care should be implemented.

For example, ?increasing the number of female providers, particularly those of the patient?s race/ethnicity, is an important step in breaking down resistance to screening,? it concluded. Furthermore, the report called for improved insurance coverage and reimbursement for cancer-related services.

Still, especially in developing countries, the road to curbing cervical cancer is barely even under construction. Screening and treatment efforts have been on the rise, but most women still have little or no access. Reports show that by the time women with complications of cervical cancer do manage to consult a health care provider, the disease is usually at a late stage for which treatment, and even pain relievers, are most often ineffectual.

According to a recent study out of South Africa, ?cervical cancer remains the most common malignancy among females in countries of low income, mainly due to a lack of screening. Responsible factors are centered around inadequacies of the Pap smear: high cost, low sensitivity, the need of a laboratory with high human expertise and a demanding logistic system for mass screening. No alternative screening method seems to be clearly advantageous.?

With the help of the Bill & Melinda Gates Foundation, however, some progress is on the way. In 1999, the foundation made a five-year, $50 million grant to prevent cervical cancer in developing countries. It established the Alliance for Cervical Cancer Prevention, an association linking organizations around the world in the cervical cancer battle, and began identifying international interventions. For example, last June, the Gates Foundation gave the World Health Organization (WHO) $7 million as part of an integrated effort to accelerate the development of vaccines to protect against cervical cancer. It also provided funding to the International Agency for Research on Cancer, Harvard University and the Program for Appropriate Technology in Health (PATH) for a total of $12.9 million in grants.

According to the WHO, its Initiative for Vaccine Research will create a network to facilitate vaccine licensing and monitoring in developing countries and to harmonize and standardize laboratory procedures. It will also create a policy platform and, in consultation with regions and countries, set guidelines for future HPV vaccine introduction.

The International Agency for Research on Cancer will collect new data on HPV in low-resource countries in Asia, Africa and Eastern Europe. Harvard plans to develop models to evaluate both the population impact and cost-effectiveness of different HPV vaccination strategies, and PATH will work to develop partnerships with the private sector, develop a case for investing in HPV vaccine, address country- and region-specific programmatic issues and identify information needs.

?It?s logistically challenging,? says Jacqueline Sherris, a researcher and strategic program leader for reproductive health at PATH. One reason is ?the vaccines are for young women, or you could say, older children, who have not yet become sexually active.? Traditionally, reaching these 13- and 14-year-olds has been difficult. Not only do they often have to travel long distances to reach health care providers, they must also overcome societal attitudes that deny the need for them to get a vaccine against a sexually transmitted disease.

Even in the United States, early responses from conservative groups to the news of a cervical cancer vaccine were negative. ?Abstinence is the best way to prevent HPV,? Bridget Maher of the Family Research Council was quoted as saying in an article posted on newscientist.com a year ago. ?Giving the HPV vaccine to young women could be potentially harmful because they may see it as a license to engage in premarital sex.?

Six months later, however, the Family Research Council reversed itself, posting a statement on its Web site that said, ?Any medical advance in this area holds potential for helping to protect the health of millions of Americans and helping to preserve the lives of thousands of American women.? While still promoting the importance of sexual abstinence and monogamy, the organization now welcomes news of the vaccine.

It?s joined by the Medical Institute for Sexual Health, another traditionally conservative organization. After convening a panel to review the potential vaccine, it announced its support for universal use. On its Web site, the Medical Institute endorses the development and use of vaccines against HPV and other sexually transmitted infections.

?Once you explain to people that the vaccine is a safe, straightforward way to prevent a common disease,? Sherris says, ?the concerns and challenges go away.

Gostout agrees. ?The initial talk of the vaccine promoting sex has been largely dispelled though education. It?s difficult to turn your back on this science.?

?This is definitely a big advance,? says Frances Kissling, president of Catholics for a Free Choice. ?It?s not about abortion. It?s not about contraceptives -- it?s about disease prevention. It?s about healthy sex. I don?t hear much controversy about it.?

But will key constituencies, including parents, insurance companies, pediatricians and gynecologists buy into the program?

Apparently they will. A 2004 survey of Fellows of the American College of Obstetricians and Gynecologists found gynecologists were willing to

include the vaccine in their office practice.

Parents in the United States were also found to be on board. Research presented at the 2005 annual meeting of the Society of Gynecologic Oncologists last March found that ?a vast majority of women would be willing to take a cervical cancer vaccine themselves and would allow it to be administered to their children.?

In a study from the University of Cincinnati College of Medicine last December, family physicians reported their intention to recommend HPV vaccines. Reproductive health organizations such as the Gynecologic Cancer Foundation have also thrown their support behind wide distribution of the vaccine. They?re recommending the FDA make the vaccination mandatory. According to Gostout, this will prompt the insurance companies and government agencies to pay for it.

From an economic standpoint, while the vaccines are expensive, Gostout says, ?This is an expense worth every penny.? The drugs are sure to be a financial boon for the companies that make them, but there?s also a tangible sense of altruism in the push for approval. ?They are as committed to this and as passionate about it as we are,? Gostout says. ?That?s unique among companies.?

But the fact that cervical cancer hits women in their prime and that when advanced life expectancy is measured in months, researchers have been compelled to find solutions for prevention. ?Cervical cancer is a bad disease,? Gostout says. ?If it?s caught early enough, 85 percent of cervical cancer cases can be successfully treated. But once it has advanced, it?s deadly. We don?t have good ways to fight it at that point.?

Gostout says that as a cancer doctor and researcher, cervical cancer is the hardest for her to see. ?This is the one that most often breaks my heart,? she says. ?Lung and colon cancer are different; they hit people later in life. But cervical cancer takes such vibrant women. One day they are fully living, the next they have this devastating disease. It?s a painful, miserable death. For women who aren?t screened, symptoms don?t appear until the cancer has advanced. Life expectancy is then measured in months. It?s almost hopeless.?

But now Gostout says there is good reason to be hopeful. ?We are in a new era of cancer prevention,? she says. ?Now we just need to roll up our sleeves and get working.?

RESOURCES

Women?s Cancer Network, www.wcn.org.

At this Web site, you can take the Cancer Risk Assessment Survey. This confidential, interactive survey, developed by cancer experts, will help you to identify your risk level for developing breast, ovarian, endometrial, cervical, vulvar and vaginal cancer.

National Cervical Cancer Coalition,

www.nccc-online.org

National Cervical Cancer Public Education Campaign, www.cervicalcancercampaign.org

American Cancer Society, www.cancer.org

Centers for Disease Control and Prevention, www.cdc.gov/cancer/nbccedp/index.htm

RISK FACTORS

The vast majority of women infected with an HPV never develop cervical cancer, which suggests that additional factors acting in conjunction with HPV influence the risk of disease development. Cofactors associated, to various extents, with the development of invasive cervical cancer include:

1. High parity Compared to women who had never given birth, those with three or four full-term pregnancies had 2.6 times the risk of developing cervical cancer; women with seven or more births had 3.8 times the risk. Further, because parity appears to be a risk factor for cervical cancer, the use of oral contraceptives may reduce the risk of cervical cancer attributable to parity.

2. Smoking This is among the most consistently identified environmental cofactors likely to influence the risk of cervical cancer. Studies show at least a twofold risk for current smokers compared to non-smokers.

3. HIV Women infected with HIV are more readily infected with high-risk HPV types and are more likely to develop precancerous lesions (and develop them more rapidly) than HIV-negative women in the same age category. Women who are coinfected with HPV and another sexually transmitted agent, such as Chlamydia trachomatis or herpes simplex virus-2 (HSV-2), have a threefold increased risk of developing cervical cancer than are women who are not coinfected.

4. Low socio-economic status This is recognized as a risk factor for many health problems, including cervical cancer, particularly in low-resource settings.

Source: The Alliance for Cervical Cancer Prevention, May 2004

Published: April 01, 2006
Issue: Spring 2006