Cervical Cancer Vaccine Offers Cross Protection against Multiple HPV Types

CHICAGO-A three-dose regimen of the quadrivalent human papillomavirus (HPV) vaccine Gardasil-designed to prevent infection with HPV types 6, 11, 16, and 18-also provides a significant degree of cross-protection against other common oncogenic strains of the virus, researchers reported here at the International Conference on Antimicrobial Agents and Chemotherapy (ICAAC).

In ongoing trials of more than 11,000 women age 15 to 26, the vaccine offered nearly 40% cross-protection against 10 non-vaccine oncogenic types of HPV-31, 33, 35, 39, 45, 51, 52, 56, 58, and 59, said chief investigator Darren R. Brown, MD, Professor of Medicine, Microbiology, and Immunology at Indiana University School of Medicine, who reported the findings of the prespecified, subgroup analysis of the prospective Females United To Unilaterally Reduce Endo/ectocervical Disease (FUTURE) I and II trials.

38% Cross-Protection

Dr. Brown's previous research, presented earlier this year at the American Association for Cancer Research Annual Meeting, showed that the vaccine continues to offer nearly 100% protection against HPV types 16 and 18, together responsible for about 70% of cervical cancer cases, five years following administration.

The vaccine also protects against infection with HPV types 6 and 11, responsible for about 90% of genital warts.

The new study shows that the vaccine also:

▪ Provides 38% protection against 10 HPV strains responsible for another 20% of cervical cancer cases.

▪ Offers 45% protection against persistent infection from types 45 and 31, the third and fourth most common HPV strains.

▪ Is 62% effective against cervical intraepithelial neoplasia 2/3 or adenocarcinoma in situ caused by those two strains. Dr. Brown noted that this was the primary endpoint of the analysis.

▪ Offers 28% protection against persistent infection from types 31, 33, 45, 52, and 58.

▪ Is 43% effective against cervical intraepithelial neoplasia 2/3 or adenocarcinoma in situ caused by those two strains.

This is the first demonstration of cross-protection for any HPV vaccine against precancerous lesions of the cervix. It really affords an extra degree of protection for young women who have been vaccinated, he said.

All Related

Dr. Brown said that it's not a surprise that the vaccine offers protection against additional types of HPV, as they are all related.

For example, 31 is a close cousin of 16. So you would expect some, but not complete, protection against additional subtypes, which is what we found, he explained.

The vaccine stimulates the production of neutralizing antibodies that prevent the virus from entering cells, he noted. The different degrees of cross-protection against various HPV types are probably due to the varying levels of antibody generated, he said.

The study was funded by the vaccine's manufacturer, Merck & Co., Inc.

Noteworthy from Public Health Point of View

Scott Hammer, MD, the Harold C. Neu Professor of Medicine, Professor of Public Health, and Chief of the Division of Infectious Diseases at Columbia University and Cochairman of the conference, said that the findings are noteworthy from a public health point of view.

We didn't know if the type-specific protection stopped at the water's edge or if there would be cross-protection. The new study offers strong support that Gardasil is about 35 to 40 percent effective in preventing infection with other types of human papilloma virus that cause cervical cancer, he said.

Carolyn D. Runowicz, MD, Director of the Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center and a past president of both the American Cancer Society and the Society of Gynecologic Oncologists (SGO), said the findings are good news because there is some cross protection against other HPV types-It's obviously not 100 percent protection, but you would not expect that.

This is what we were hoping would happen but didn't know until we saw these data, she said.

Dr. Runowicz added that the findings support recommendations that women who have not been sexually active are the prime candidates for the vaccine.

Beth Y. Karlan, MD, another past president of SGO and Director of the Women's Cancer Research Institute and the Gilda Radner Hereditary Cancer Detection Program at Cedars-Sinai Medical Center in Los Angeles, said, The public health message is real and groundbreaking. For the first time we can vaccinate our children against cervical cancer. This is really a paradigm shift.

While the prior data demonstrated a 70% reduction in the risk of cervical cancer, these new data elevate that reduction because of the halo effect to include 10 additional oncogenic HPV types. Plus, the vaccine provides significant risk reduction for venereal warts.