Drugs Log

Merck, the manufacturer of the quadrivalent HPV vaccine Gardasil, already being administered in many countries to girls as young as 12 to help prevent cervical cancer, has announced findings of a trial that shows it is also effective for women as old as 45.

The drugmaker announced details of an investigational study where Gardasil reduced the rate of infection due to four strains of sexually transmitted human papillomavirus (HPV) in women up to the age of 45, at the 24th International Papillomavirus Conference (IPC) in Beijing, China, yesterday, Sunday November 4th.

Gardasil is a quadrivalent, recombinant vaccine designed to reduce infection due to HPV strains 6, 11, 16 and 18 and trials have already shown it be to effective for girls and women aged 9 to 26 years in the prevention of cervical cancer, precancerous or dysplastic lesions, and genital warts. In trials it was shown that by protecting against the four HPV strains that cause most of the diseases, it prevented 70 per cent of cervical cancer cases and 90 per cent of genital warts cases.

In the latest international, multi-center, trial involving more than 3,800 women, the three dose vaccine was also shown to prevent 91 per cent of persistent infection, low-grade cervical abnormalities and pre-cancers, as well as external genital lesions caused by the four strains of HPV in women aged 24 to 45.

The women in the trial had no history of genital warts; hysterectomy; LEEP (loop electrosurgical excision procedure) or biopsy-diagnosed cervical HPV disease in the five years previous to enrollment. They were also all free of infection from at least one of the four HPV strains when they were enrolled in the study and remained free of infection from the same strains when they finished the three doses of vaccine or placebo.

Dr Eliav Barr, executive director of Biologics Clinical Research and head of the HPV Vaccine Program, Merck Research Laboratories said in a press statement that:

“Women remain at significant risk for acquiring HPV infections and developing HPV-related diseases throughout their lifetime.”

“These data build on the clinical program for GARDASIL and will help us to understand the potential benefit that GARDASIL may have in women through age 45,” added Barr.

The drugmaker will be submitting the results of the trial with an application to the US Food and Drug Administration (FDA) before the end of the year to extend approved indication of the vaccine for women up to 45. The FDA approved Gardasil in June 2006 and the vaccine is recommended for use in the US for girls and women aged 11 to 26 by the Centers for Disease Control and Prevention (CDC).

Researchers tracked the incidence of persistent infection, cervical intraepithelial neoplasia (CIN) and external genital lesions caused by the four HPV strains (6, 11, 16 and 18) and diseases caused by HPV 16 and 18.

The results showed that:

• There were 4 cases of of persistent infection, CIN or external genital lesions (genital warts and vaginal and vulvar lesions) caused by HPV 6, 11, 16 or 18 in the vaccine group compared to 41 cases in the placebo group.
• This equated to a 91 percent reduction in incidence (at 95 per cent confidence interval, or CI) over an average follow up of 1.65 years.
• There were 4 cases of of persistent infection, low-grade cervical abnormalities and pre-cancers, and external genital lesions caused by HPV types 16 and 18 alone, in the vaccine group, and 23 cases in the placebo group.
• This equated to a 83 per cent prevention rate (at 95 per cent CI) for diseases caused by HPV types 16 and 18 alone.
• The vaccine prevented 100 per cent of persistent infections, external genital lesions, and low-grade cervical abnormalities and pre-cancers, caused by HPV strains 6 and 11.
• It also reduced abnormal Pap test results related to HPV 16 and 18 by 94 percent (at 95 per cent CI).
• The most common adverse events related to the injection site (redness, pain, pruritis, swelling, warmth) and were higher in the vaccine than the placebo group (76.4 versus 64.2 per cent).

Gardasil is widely available in the US, and all the country’s 55 immunization programs have adopted it. In addition to the US, the vaccine is approved in 85 countries throughout the world, including all of the European Union, Australia, Brazil, Canada, Mexico, New Zealand and Taiwan.

HPV is a common infection, and it is estimated that some 20 million people in the US have it and that 80 per cent of women will have acquired it by the age of 50. In most people HPV is self-limiting and disappears by itself. But for some women, the higher risk HPV strains can lead to cervical cancer if untreated.

Nearly half a million cases of cervical cancer are diagnosed worldwide every year, and 240,000 women die from it each year. It is the second most common cause of cancer death in women worldwide.

In June 2006, the Advisory Committee on Immunization Practices (ACIP) voted to recommend the first vaccine developed to prevent cervical cancer and other diseases in females caused by certain types of genital human papillomavirus (HPV). The vaccine, Gardasil®, protects against four HPV types, which together cause 70% of cervical cancers and 90% of genital warts.

The Food and Drug Administration (FDA) licensed this vaccine for use in girls/women, ages 9-26 years. The vaccine is given through a series of three shots over a six-month period.

Some general information about genital HPV & Cervical Cancer

Genital HPV is a common virus that is passed on through genital contact, most often during vaginal and anal sex. About 40 types of HPV can infect the genital areas of men and women. While most HPV types cause no symptoms and go away on their own, some types can cause cervical cancer in women. These types also have been linked to other less common genital cancers— including cancers of the anus, vagina, and vulva (area around the opening of the vagina). Other types of HPV can cause warts in the genital areas of men and women, called genital warts.

How is HPV related to cervical cancer?
Some types of HPV can infect a woman’s cervix (lower part of the womb) and cause the cells to change. Most of the time, HPV goes away on its own. When HPV is gone, the cervix cells go back to normal. But sometimes, HPV does not go away. Instead, it lingers (persists) and continues to change the cells on a woman’s cervix. These cell changes (or “precancers”) can lead to cancer over time, if they are not treated.

How common is HPV?
At least 50% of sexually active people will get HPV at some time in their lives. Every year in the United States (U.S.), about 6.2 million people get HPV. HPV is most common in young women and men who are in their late teens and early 20s.

Anyone who has ever had genital contact with another person can get HPV. Both men and women can get it – and pass it on to their sex partners- without even realizing it.

How common is cervical cancer in the U.S.? How many women die from it?
The American Cancer Society estimates that in 2006, over 9,700 women will be diagnosed with cervical cancer and 3,700 women will die from this cancer in the U.S.

How common are Genital Warts?
About 1% of sexually active adults in the U.S. (about 1 million people) have visible genital warts at any point in time.

Is HPV the same thing as HIV or Herpes?
HPV is NOT the same as HIV or Herpes (Herpes simplex virus or HSV). While these are all viruses that can be sexually transmitted— HIV and HSV do not cause the same symptoms or health problems as HPV.

Can HPV and its associated diseases be treated?
There is no treatment for HPV. But there are treatments for the health problems that HPV can cause, such as genital warts, cervical cell changes, and cancers of the cervix, vulva, vagina and anus.

Other ways to prevent HPV and Cervical Cancer

Another HPV vaccine is in the final stages of clinical testing, but it is not yet licensed. This vaccine would protect against the two types of HPV that cause most (70%) cervical cancers.

Are there other ways to prevent cervical cancer?
Regular Pap tests and follow-up can prevent most, but not all, cases of cervical cancer. Pap tests can detect cell changes in the cervix before they turn into cancer. Pap tests can also detect most, but not all, cervical cancers at an early, curable stage. Most women diagnosed with cervical cancer in the U.S. have either never had a Pap test, or have not had a Pap test in the last 5 years.

There is also an HPV DNA test available for use with the Pap test, as part of cervical cancer screening. This test is used for women over 30 or for women who get an unclear (borderline) Pap test result. While this test can tell if a woman has HPV on her cervix, it cannot tell which types of HPV she has.

Are there other ways to prevent HPV?
The only sure way to prevent HPV is to abstain from all sexual activity. Sexually active adults can reduce their risk by being in a mutually faithful relationship with someone who has had no other or few sex partners, or by limiting their number of sex partners. But even persons with only one lifetime sex partner can get HPV, if their partner has had previous partners.

It is not known how much protection condoms provide against HPV, since areas that are not covered by a condom can be exposed to the virus. However, condoms may reduce the risk of genital warts and cervical cancer. They can also reduce the risk of HIV and some other STIs, when used all the time and the right way.