New vaccine to prevent cervical cancer now available
The first vaccine developed to prevent cervical cancer is now being offered at UK HealthCare and elsewhere in the nation. The vaccine, Gardasil, which is manufactured by Merck & Co. Inc., protects against infection from certain strains of the human papilloma virus (HPV)—a sexually transmitted disease that accounts for 70 percent of the cases of cervical cancer and 90 percent of all cases of genital warts. The Food and Drug Administration granted approval for Gardasil in June 2006, for use in females 9 to 26 years of age.
Kentucky has the second highest cervical cancer death rate in the nation.
Worldwide, HPV infection causes about 470,000 cases of cervical cancer a year and 233,000 deaths, most of them in developing countries where PAP tests have not been implemented. According to the American Cancer Society, up to 11,000 new cases of cervical cancer will be diagnosed in the United States in 2007, with 3,600 deaths. Kentucky has the second highest cervical cancer death rate in the nation.
HPV is the most common sexually transmitted disease in the country. Up to 70 percent of the sexually active men and women become infected at some point in their lives, although most infections are benign. A recent article in JAMA (Journal of the American Medical Association) reports that nearly 27 percent of females age 14 to 59 are infected with HPV. The 20 to 24 age group has the highest incidence rate—almost 45 percent.
There are more than 35 types of HPV that affect the genital tract. Gardasil was developed to target types 16 and 18, which cause most cervical cancers; and types 6 and 11, the main cause of genital warts. It contains no live virus and is for prevention only.
How studies were conducted
Beginning in 2002, four clinical trials were conducted in 21,000 women to test how well Gardasil works in women between the ages of 16 and 26. The studies also evaluated whether the vaccine can protect women already infected with HPV.
In one of the most recent studies, reported in the May 2005 edition of the British medical journal The Lancet, 552 women in the United States, Europe and Brazil between the ages of 16 and 23 were given either the vaccine or a placebo. The women were not pregnant, had no previous abnormal Pap smears and had no more than four male sexual partners in their lifetime. The study did not exclude women with previous HPV infections.
Researchers tested the effectiveness of the vaccine in reducing HPV 6, 11, 16 and 18 infections, cervical precancers (dysplasia), cervical cancer and genital warts. Participants were randomized to receive three injections of the vaccine or the placebo over a six-month period. For the next 30 months they underwent gynecological exams and sampling for HPV infection.
Incidence of persistent HPV infection or cervical dysplasia fell by 90 percent in vaccinated women.
Over the two and a half years of follow-up after vaccination, the incidence of persistent HPV infection or cervical dysplasia fell by 90 percent in women who had been vaccinated, as compared with those who received the placebo. Women who were not HPV-negative throughout the vaccination period were not similarly protected, indicating that the vaccination works only prior to infection. The study did not look at cervical cancers since they typically take at least 10 years to develop and are preceded by precancerous lesions.
Although further research is needed to determine how long protection lasts, women in the study still had high levels of serum antibodies from the vaccine nearly three and a half years after receiving the injections.
The researchers suggest that Gardasil might be most effective in 10- to 13-year-old girls who are likely to be HPV negative.
“The expectation that the vaccine will reduce cervical cancer rates, the fact that HPV infection affects most women, and the lack of effective means to prevent HPV infection in sexually active people lend support to the vaccination in preadolescents,” they wrote.
The Centers for Disease Control recommends that girls 11 to 12 receive the three-shot regimen, with catch-up vaccinations for those 13 to 26 who have not been vaccinated previously. Many states are considering legislation that would make HPV vaccinations mandatory.
Merck is conducting more clinical trials to gauge the long-term effectiveness of Gardasil and the vaccine’s general safety. The previous studies have shown that pain at the injection site and headaches were the main side effects. The manufacturer is also studying the safety and effectiveness of Gardasil in men.
Another manufacturer, GlaxoSmithKline is developing its own HPV vaccine, Cervarix, and plans to apply for FDA approval later this year.
For more information, see:
- Prophylactic quadrivalent human papillomavirus (types 6,11,16, and 18) L1 virus-like particle vaccine in young women, The Lancet Oncology, v. 6, no. 5, May 2005
- Prophylactic human papillomavirus vaccines, The Journal of Clinical Investigation, v. 116, no. 5, May 2006
- Human papillomavirus infection, JAMA, v. 297, no. 8, February 28, 2007
- Prevalence of HPV infection among females in the United States, JAMA, v. 297, no. 8, February 28, 2007
- Cervical cancer, Health Information, UK HealthCare
- Gynecological health, Health Information, UK HealthCare
UK HealthCare Cancer Services - Markey Cancer Center
For more information, or to make an appointment with a UK HealthCare physician, please call UK Health Connection at 1-800-333-8874.
What the news means for you
Christopher P. De Simone, MD
Vaccine effective only prior to HPV infection
I’m very pleased with the development of the new vaccine for cervical cancer. All of the studies have shown that its efficacy exceeds 90 percent. It’s a great boon for medicine; however, I don’t think it’s going to be the massive cure that people think it will be. The vaccine works only in preventing disease among women who have not acquired the HPV virus through sexual relations. Once a woman has the virus, it’s too late to use the vaccine.
“HPV infection is something we all have. . . . about 70 percent of the population, both men and women, will have had the HPV virus by the time they’re 50.”
Preliminary studies indicate that the vaccine confers protection for about 18 to 20 months. However, it hasn’t been around that long so it’s hard to predict the long-term effects. Researchers think it will last a lifetime. There has been talk of a booster as well. But until we get long-term follow up of the women who’ve had the shots, we won’t know that.
Prevalence of HPV
Most of us have a connotation that you’re less than clean if you have a sexually transmitted disease, but HPV infection is something we all have. It’s not something you get because you made a “poor choice.” We know that about 70 percent of the population, both men and women, will have had the HPV virus by the time they’re 50.
There are about 100 different strains of the HPV virus, roughly 35 of them affecting the genital area. Other HPV strains cause different problems. Plantar warts that appear on the hands, for example, are caused by an HPV virus. There are so many strains, it’s very hard to develop an immunity to all of them. If a woman has HPV 31, a strain which causes cervical cancer, Gardasil won’t protect against that.
Detecting and treating disease
Cervical cancer is a long disease process that starts with a person acquiring the HPV virus. The virus then has to transform the cell into dysplasia and then the dysplasia evolves into a cancer. The time between acquisition of the virus and the development of squamous cancer of the cervix is approximately 10 years. Adenocarcinoma is a glandular cancer that takes a shorter period of time to develop, but it is much less common.
“Cervical cancer is a long disease process that starts with a person acquiring the HPV virus.”
The longer a person goes without treatment for dysplasia, the more likely she is to develop cervical cancer. That’s why Pap smears are so important for screening. The Pap smear works very well in detecting cervical dysplasia before it becomes cancer.
Dysplasia is graded as mild, moderate and severe and treated accordingly. The usual treatment for moderate to severe dysplasia is LEEP – loop electrosurgical excision procedure, an outpatient procedure. A wire with electricity running through it is used to cut away areas of abnormal cells on the cervix. Most cases of mild dysplasia will regress; about 60 percent within one year. Generally, a woman’s immune system will take care of the condition without treatment. If it persists beyond two years, then it should be treated.
If the dysplasia is severe and goes untreated, there is a 12 percent risk the patient will develop cancer within two years. That risk goes up to 40 percent within five years and 70 to 80 percent in eight years.
Administering the vaccine
Since the vaccine works best in young women before sexual activity, I believe this will chiefly be an issue for pediatricians and family care physicians. My personal preference would be that young men get it as well. We know that they harbor the virus just as much as women, although men are usually asymptomatic.
I would advise parents to look at the long-term consequences. If we can prevent cervical cancer and cervical dysplasia, I don’t see why we shouldn’t administer the vaccine before sexual activity.
Dr. De Simone is a gynecologic oncologist with the UK Markey Cancer Center and assistant professor of obstetrics and gynecology in the UK College of Medicine.