The recommendations for use of the Gardasil vaccine, which provides protection against two strains of the human papillomavirus responsible for most cases of cervical cancer, were issued by the FDA’s Advisory Committee on Immunization Practices in June 2006.

“The guidelines state that routine vaccination with Gardasil is recommended for 11- and 12-year-old females and for females ages 13 to 26 who have not previously been vaccinated or who have not completed the full series, and that vaccination with Gardasil can be started at nine years of age,” Merck said in a news release.

“Because of the ease of weekly dosing and the lower cost of outpatient cisplatin administration in combination with radiation therapy for the treatment of locally advanced cervical cancer,” Dr. Mark H. Einstein said, there has been “a trend to use outpatient weekly cisplatin despite no randomized, controlled comparison trials showing equivalency to inpatient 5-day regimens.”

In the January issue of Cancer, Dr. Einstein of Montefiore Medical Center, the Bronx and colleagues note that cisplatin administration concomitant with radiotherapy for the treatment of locally advanced cervical cancer has evolved from a 5-day per 21-day inpatient regimen developed in the mid-1980s to a weekly outpatient regimen.

To examine possible differences in outcome, the researchers compared data on 50 patients who underwent the 5-day regimen with cisplatin at 20 mg/m² every 21 days along with radiotherapy, and a further 27 patients who had outpatient weekly cisplatin at 40 mg/m² concomitant with radiotherapy.

After controlling for stage, 3-year progression-free survival was 90% in the 5-day group and 76% in the weekly group, a significant difference.

In addition, adjusting for stage, age, and completion of treatment, the risk of treatment failure among the weekly group was 3.46 times higher than that in the 5-day group. The weekly group also had a 3.43 times higher risk of developing acute toxicities than the 5-day group.

“We found,” continued Dr. Einstein, “that the way most of us who treat cervical cancer in this country are currently administering chemotherapy — as an outpatient — imparts worse survival and more toxicity than the way we used to administer cisplatin — as an inpatient — over 5 days.”

“We believe,” he concluded, “these important findings merit a prospective, randomized trial to determine if a true difference between these two chemotherapy regimens exists.”

Cervical cancer is currently the second-leading cause of cancer death among women worldwide. The American Cancer Society estimated that over 9,000 women would be diagnosed with the disease in 2006 and over 3,000 would die from it in the U.S. alone.

Cervical Cancer Can Be Prevented
Cervical cancer can be prevented in most cases. Women can great reduce their cervical cancer risk by getting a regular Pap smear. A Pap smear is a highly effective cervical cancer screening tool, detecting abnormal cervical changes long before they become cancerous.

However, the Pap smear is not a diagnostic test, and regular Pap smears are needed to detect any abnormal changes that may become cancerous.

The HPV vaccine, approved by the FDA in June 2006, is also a highly effective means of cervical cancer prevention. The human papillomavirus (HPV), a virus transmitted through sexual skin-to-skin contact, is known to cause cervical cancer in women.

The vaccine works by preventing four strains of HPV. Two of the strains that the vaccine protects against are known to cause cervical cancer. The other two strains that are covered are responsible for genital warts.

What You Can Do to Keep Your Cervix Healthy
Get Screened: A regular Pap smear is essential in detecting cervical abnormalities. The American College of Obstetricians and Gynecologists recommend that a woman have her first Pap smear about three years after her first sexual intercourse or by age 21, whichever comes first. How often you have a Pap smear depends on your age, previous Pap results, and overall cervical cancer risk factor. Remember, annual exams are still necessary even if you do not have a Pap smear every year.

Get Vaccinated: The HPV vaccine is an excellent method of preventing cervical cancer. In clinical trials, Gardasil was 100 percent effective against HPV strains 16 and 18, which are responsible for 70 percent of cases of cervical cancer. It was also 99 percent effective against HPV strains 6 and 11, which are responsible for 90 percent of cases of genital warts.

Gardasil is available to to young women ages nine to 26, with a target age of 11 to 12 years. Talk to your doctor to see if you are eligible to receive the vaccine.

Abstain from Sexual Contact and Intercourse or Limit the Amount Sexual Partners You Have: HPV is transmitted through both sexual intercourse and sexual skin-to-skin contact, so no penetration is needed to contract HPV. Abstaining from all sexual activity is an ideal method of HPV prevention, yet unrealistic for most adults. Limiting the amount of sexual partners you have and staying in a monogamous relationship can reduce your risk factor for developing HPV.

Quit Smoking: Besides the obvious risk of developing lung cancer and heart disease, smoking affects the cervix also. Smoking has been linked to the development of cervical dysplasia and cervical cancer, especially if a woman has HPV. In fact, smokers are twice as likely to develop cervical cancer than non-smokers.

Follow your health professional’s advice about when you need to have a Pap smear. You can significantly lower your risk of full-blown cervical cancer developing by adhering to a strict schedule of having regular pelvic exams, as directed by your health care provider, throughout your lifetime.

Even if you’ve had a hysterectomy, regular pelvic exams are necessary to detect other diseases, as well as cancers of the vulva or vagina, which occur more frequently post-hysterectomy.

What Increases Your Risk for Cervical Cancer?
The single greatest risk factor for the development of cervical cancer is the human papilloma virus or HPV. This makes HPV the cause of nearly 100 percent of cervical cancers. While there are about 100 types of HPV, only 20 types of HPV factor into future cervical cancer. The two types of HPV that are precursors to the majority of cervical cancers are HPV 16 and HPV 18. Although the majority of women who get cervical cancer also have HPV, not every woman who either has or has had previous diagnosis of the human papilloma virus will ever have cervical cancer. However, HPV16, HPV18, or another of the 20 types that may lead to cervical cancer is typically present in women diagnosed with cancer of the cervix.
Having or having had a previous diagnosis of HPV, in addition to having one or more of the following risk factors for cancer of the cervix can significantly affects your personal risk of cervical cancer. Your answer to the following questions can help you to determine your cervical cancer risk:

Did you begin having sexual activity before age 18?

Have you had more than one sexual partner, or several sexual partners?

Has the person(s) you had sex with have sex with other partners?

Have you ever had any type of sexually transmitted disease or STD?

Are you over age 60?

Do you smoke?
For each question that you answered “yes,” your risk of cervical cancer significantly increases when you have or have ever had a diagnosis of HPV. Many times the presence of the human papilloma virus is unknown, making asking your health care provider for a HPV test during your next Pap smear essential. The recommendation for HPV testing is for women to have this test once every three years, unless your health care provider feels it’s unnecessary, or you need more frequent HPV testing. Remember, the most important thing you can do to help prevent future cervical cancer diagnosis is for you to strictly follow you health care providers instructions for future visits, and for any follow-up tests or procedures after an abnormal Pap smear result is obtained.

References: National Women’s Health Information Center NWHIC, American Cancer Society ACS, National Health Institutes NHI

While some cases of cervical cancer cannot be prevented, there are many things a woman can do to reduce her risk of developing cervical cancer.

How to Reduce Your Risk of Cervical Cancer

1.Get a regular Pap smear. The Pap smear can be the greatest defenses for cervical cancer. The Pap smear can detect cervical changes early before they turn into cancer. Check cervical cancer screening guidelines to find out how often you should have a Pap smear, or check with your doctor.

2.Limit the amount of sexual partners you have. Studies have shown women who have many sexual partners increase their risk for cervical cancer. They also are increasing their risk of developing HPV, a known cause for cervical cancer.

3.Quit smoking or avoid secondhand smoke. Smoking cigarettes increases your risk of developing many cancers, including cervical cancer. Smoking combined with an HPV infection can actually accelerate cervical dysplasia. Your best bet is to kick the habit.

4.If you are sexually active, use a condom. Having unprotected sex puts you at risk for HIV and other STD’s which can increase your risk factor for developing cervical cancer.

5.Follow up on abnormal Pap smears. If you have had an abnormal Pap smear, it is important to follow up with regular Pap smears or colposcopies, whatever your doctor has decided for you. If you have been treated for cervical dysplasia, you still need to follow up with Pap smears or colposcopies. Dysplasia can return and when undetected, can turn into cervical cancer.

6.Get the HPV vaccine. If you are under 27, you may be eligible to receive the HPV vaccine, which prevents high risk strains of HPV in women. The HPV vaccine, Gardasil, was approved by the FDA to give to young girls as young as 9. The vaccine is most effective when given to young women before they become sexually active.

1. Practice Safe Sex
Safe sex is not only essential for preventing pregnancy, but also for sexually transmitted diseases like the human papillomavirus (HPV). HPV is a common sexually transmitted virus and is the primary cause of most cases of cervical cancer. You can reduce your risk of being infected with HPV by using a condom during sexual intercourse. A condom won’t provide 100-percent protection against HPV, but studies show that condoms do provide some protection against HPV. You are much better off with your partner wearing a condom than not wearing one.

2. Limit How Many Sexual Partners You Have
Practicing safe sex is more than just wearing a condom. It also means limiting the amount of sexual partners you have in your lifetime. Having multiple sexual partners increases your risk of being infected with HPV and other sexually transmitted diseases.

3. Get Screened Regularly for Cervical Cancer
Getting a regular Pap smear is a highly effective way to reduce your risk of cervical cancer. The Pap smear is a simple test that can detect abnormal cervical changes long before they become cancerous. The key to the effectiveness of the Pap smear is having it done regularly. How often you need a Pap smear varies from woman to woman, based on age, previous pap smear results, and your cervical cancer risk factor. Always consult with your doctor about how often you should be having Pap smears.

If your Pap smear results are abnormal, be sure to follow up with your doctor’s recommendations. This could mean more frequent Pap smears or a colposcopy, an exam that allows the cervix to be viewed more closely.

4. Be a Non-Smoker
Simply put, smoking offers no health benefits. It is common knowledge that smoking affects the lungs, but did you know that smoking can affect your cervix? Studies show that smoking can actually speed up the process of cervical damage caused by HPV. Quitting now greatly reduces your risk of several types of cancer, including cervical cancer.

5. Get Immunized Against HPV
HPV is a common sexually transmitted virus known to cause cervical cancer in women. Fortunately, there is an approved vaccine that not only protects against high risk strains, but also against two strains known to cause genital warts. Gardasil is available to women under 27, with a target age of 11 to 12 years of age. The vaccine is given in a series of three shots over a course of six months. It is most effective when given to young women before they become sexually active.

But the HPV vaccine is no magic bullet: it has the potential to substantially reduce the prevalence of cervical cancer, but not to eradicate it. Now that an HPV vaccine is already on the market, while a second is expected to receive regulatory approval soon, health professionals and health-care policymakers face tough decisions.

Questions such as ‘who should get the vaccine and at what age?’, ‘how to include HPV vaccination in a comprehensive cervical cancer control programme?’ and ‘which sustainable funding mechanisms should be in place?’ are just the start.

Such decisions may be easier for developed countries which have data on HPV and cervical cancer prevalence, existing vaccination programmes and ample clinical trial data on the HPV vaccine itself, while developing countries may not have a complete set of epidemiological data or a mechanism to deliver the vaccine.

But even for developed countries, cost is a major barrier to making the vaccine widely available.

In June 2006, Merck’s Gardasil received approval from the US Food and Drug Administration and, shortly afterwards, was provisionally recommended by the US Advisory Committee on Immunization Practices for girls and women aged nine to 26.

As of the end of 2006, the vaccine had been approved in 49 countries worldwide, with more expected to join the list this year. The quadrivalent vaccine gives 100% protection against infection from HPV types 16 and 18, which are responsible for around 70% of all cervical cancers. It also protects against HPV types 6 and 11 that cause genital warts. GlaxoSmithKline Biologicals applied to the European Agency for the Evaluation of Medicinal Products for international regulatory approval in March 2006 to market its bivalent vaccine Cervarix for HPV types 16 and 18.

“There are challenges for countries in terms of cost and so on, but this vaccine is unique and offers tremendous possibilities.”
Dr Teresa Aguado, WHO’s coordinator for the Initiative for Vaccine Research, Product Research and Development team.

Meanwhile, the World Health Organization (WHO) has been developing information that countries can use to formulate their policies on HPV vaccination.

“Vaccines have been tested in North America, Latin America, Europe, to some extent in Asia, but not in Africa yet,” said Dr Teresa Aguado, WHO’s coordinator for the Initiative for Vaccine Research, Product Research and Development team.

Last year WHO made available to countries policy and programme guidance notes and technical briefing notes on introducing HPV vaccines. The documents drive home the need to educate governments, health professionals and the public about both viruses and vaccines, and the importance of collaboration between reproductive health, immunization, child and adolescent health and cancer control programmes.

“The guidelines make it clear that partnership between health programmes is vital for a coordinated introduction of the vaccine,” said Dr Nathalie Broutet of WHO’s Department of Reproductive Health and Research. “Vaccine introduction gives these programmes the opportunity to deliver other interventions while immunizing against HPV.”

This year promises to be a significant one for HPV vaccination. WHO’s six regions plan meetings to discuss these issues, starting with one in April of WHO experts and government officials from the South-East Asian and Western Pacific regions.

Merck’s market price, before agents’ fees, is approximately US$ 90 a dose for a three-dose vaccination schedule in the United States, so the vaccine is expensive even by developed-world standards. “Whether it saves money will vary from country to country, but according to our analysis and others’ it’s expected to be cost-effective in the developed world,” said Dr Richard Haupt, executive director for medical affairs at Merck’s vaccine division.

“It’s important to make sure Gardasil is available globally. We’re working with international organizations like WHO, the GAVI Alliance and the Bill & Melinda Gates Foundation, organizations that are crucial in getting vaccines to the developing world, and we will engage in tiered pricing,” Haupt added.

The vaccine is also on the WHO prequalification list, which could open the door to purchases in developing countries via United Nations agencies.

Developing countries that acquire the vaccine would need to decide whether to start vaccinating females alone or both adolescent girls and boys.

The most successful vaccination programmes have been community-wide and avoid any stigma associated with single sex vaccination, but the cost may restrict HPV vaccination to girls, especially since clinical data on efficacy in boys are still being gathered.

The second question is how to reach the population. Although the vaccine is approved for women up to the age of 26, it is generally considered to be best administered at the age of nine to 13 years, before girls become sexually active and potentially exposed to HPV.

“For countries where schools are well attended by girls, a school-based vaccination programme can be the answer. Otherwise, alternatives for vaccine delivery will have to be identified and tailored to the country context,” said Aguado.

For the public and even health professionals, the first stage is education. For example, researchers found that few women in Hong Kong are aware of the role of HPV in causing cervical cancer. “HPV and cervical cancer are not that well-taught in medical or nursing school, so health-care providers need education too,” said Professor Hexter Y S Ngan of the Department of Obstetrics and Gynaecology at the University of Hong Kong Li Ka Shing Faculty of Medicine.

Hong Kong officials say they do not have enough data to decide whether to introduce the HPV vaccine widely. “There are data on the prevalence of HPV infection of certain population sub-groups in Hong Kong, but prevalence data for the general female population and some population sub-groups, such as very young females, are insufficient,” said Dr Tse Lai Yin, consultant in community medicine at the Hong Kong Department of Health’s Centre for Health Protection.

Aside from cost-effectiveness, vaccination delivery and education, the advent of the HPV vaccine has raised other issues. Promoting an anticancer vaccine and, at the same time, making it clear that HPV is a sexually transmitted infection will require deft handling in the wording of policy, education and publicity materials.

“Screening and treatment services will still be required, because the vaccines only prevent about 70% of cervical cancer cases and because it will be years, if not decades, before we see the full benefit of vaccination in terms of a reduction in the incidence of cervical cancer,” said Dr Andreas Ullrich, medical officer with WHO’s department of Chronic Disease and Health Promotion.

Countries will also need to decide what type of screening testing to use, as traditional cytology, visual methods and HPV-specific testing have their pros and cons.

“There are challenges for countries in terms of cost and so on,” said Aguado, “but this vaccine is unique and offers tremendous possibilities.”

Jane Parry, Hong Kong SAR