Research moves HPV vaccines within view

When discussing sexually transmitted diseases (STDs) with your patients, what do you tell them about human papillomavirus (HPV)? Exposure to HPV can have significant health implications, particularly for women. Some strains of the virus, including HPV-16 and HPV-18, can trigger cancers of the cervix.

About 10,370 cases of invasive cervical cancer will be diagnosed in the United States in 2005, according to the American Cancer Society (ACS).1 About 3,710 women will die from the disease in 2005, the ACS estimates.1

You soon may be able to tell women about a vaccine against HPV if scientists are able to deliver a product that is safe and effective. Merck & Co. in Whitehouse Station, NJ, and GSK Biologicals in Rixensart, Belgium, have vaccines in advanced clinical trials.

In just-published research, scientists report Merck’s trial HPV vaccine reduced the combined incidence of persistent HPV 6, 11, 16, and 18 infection and related diseases, including new cervical pre-cancers and genital warts.2 The quadrivalent vaccine, under development as Gardasil, is in Phase III clinical trials in the United States, Canada, Europe, and Latin America, says Kelley Dougherty, spokeswoman for Merck & Co. The company plans to file for Food and Drug Administration approval in the second half of 2005, with subsequent filings in Canada and Europe, she states.

Information presented at the recent International Papillomavirus Conference and Clinical Workshop in Vancouver, British Columbia, indicates that GSK’s Cervarix bivalent vaccine, targeting strains 16 and 18, also may provide cross-protection against strains 31, 45, and 52.3,4 GSK began a Phase III trial of the vaccine in 2004. It is scheduled to run for four years.5

Findings from the Gardasil study, a Phase II randomized, double-blind, placebo-controlled trial, indicate the quadrivalent HPV vaccine reduced the incidence of HPV infection and any HPV-related diseases by 90% compared with placebo.2

The trial evaluated 552 women ages 16-23 from the United States, Europe, and Brazil, who were randomized to receive the vaccine or a placebo three times over six months. The women were followed for 2.5 years, with a primary endpoint of reduction in the combined incidence of persistent HPV types 6, 11, 16, and 18 infections and related diseases, including precancerous conditions such as cervical intraepithelial neoplasia.

Thirty-six cases of disease, persistent infection, or detection of HPV on the last visit on record were seen in the placebo group compared to four in the group who received the vaccine. Of the four cases in the vaccine group, one was confirmed as persistent infection. In the other three cases, HPV was detected on the last study visit but was not later confirmed as a persistent infection.

How will vaccine be used?

If a vaccine is approved, successful implementation will require definition of the vaccine’s public health impact, cost effectiveness, the optimal age for vaccination, and the duration of protection, says Luisa Villa, PhD, head of the virology group at the Ludwig Institute for Cancer Research, São Paulo, Brazil. Villa served as lead author of the Gardasil research paper.

Lack of effective means to prevent HPV infection in sexually active adolescents and adults supports the value of vaccinating preadolescents; however, this may prove difficult because there are no systematic vaccination programs now in place for adolescents and young adults, she says.

"Ideally, this could be envisaged as a good opportunity to establish programs that would deliver contraception and STD information as well as vaccination against HPV and other diseases," Villa observes. "Besides infrastructure aspects, the physicians that will see adolescents and potentially deliver the HPV vaccine — most probably pediatricians — do not seem to be fully aware of the situation and soon-availability of the vaccine."

Another important aspect of setting up an immunization program will relate to the durability of vaccine’s induced immune responses, she says.

Thus far, the longest follow-up for the quadrivalent vaccine was 30 months after vaccination. Extension of this and other trials are under way to better assess the efficacy of the vaccine along time, Villa states. "Certainly this is one of the most important aspects that will define policies for vaccine implementation," she notes. "There is no a priori reason to think that the observed waning of antibody titers will pose a problem, but one has to show that a vaccine administered four to 10 years prior to onset of sexual activity will still be protective."

References

1. American Cancer Society. What Are the Key Statistics About Cervical Cancer? Atlanta; January, 2005. Accessed at: www.cancer.org/docroot/CRI/content/CRI_2_4_1X_What_are_the_key_statistics_for_cervical_cancer_8.asp?sitearea=.

2. Villa LL, Costa RLR, Petta CA, et al. Prophylactic quadrivalent human papillomavirus (types 6, 11, 16, and 18) L1 virus-like particle vaccine in young women: A randomised double-blind placebo-controlled multicentre Phase II efficacy trial. Lancet Oncology 2005; 6:271-278.

3. Dubin G, Colau B, Zahaf T, et al. Cross-protection against persistent HPV infection, abnormal cytology and CIN associated with HPV-16 and 18 related HPV types by a HPV 16/18 L1 virus-like particle vaccine. Presented at the 22nd International Papillomavirus Conference and Clinical Workshop. Vancouver, British Columbia; April 30-May 6, 2005.

4. Hirschler B. Glaxo’s Cervarix provides wide protection in study. Reuters, May 3, 2005. Accessed at http://today.reuters.com/news/default.aspx.

5. GlaxoSmithKline Biologicals. PATRICIA: Trial launched of new vaccine aimed at preventing cervical cancer. Press release. March 6, 2004. Accessed at: www.gsk-bio.com/webapp/PressCorner/PressDetail.jsp?PressId=10389.