HPV vaccine may offer protection from infection types not included in the vaccine

Data from two studies published in The Journal of Infectious Diseases indicate that the quadrivalent human papillomavirus vaccine may offer protection from HPV types not included in the vaccine.

Both studies were designed and sponsored by Merck.

In the first study by Brown et al, data indicated the quadrivalent HPV vaccine (Gardasil, Merck) decreased the risk for cervical intraepithelial neoplasia grades-1 to -3 associated with the non-vaccine types of HPV that cause approximately 20% of cervical cancers.

This study included data from two phase-3, double blind, placebo-controlled clinical trials (FUTURE I and FUTURE II) examining the efficacy of the HPV vaccine among 17,622 women aged 15 to 26 years. Infection endpoint data were taken from protocol 12, a substudy of the FUTURE I trial; endpoint data included here is approximately 3.6 years post-dose-one follow-up.

Participants tested negative for 14 HPV types at baseline and underwent cervico-vaginal sampling and Pap smear testing on a regular basis for four years. Biopsy samples were collected using HPV genotype sampling and histological diagnosis were determined by a pathology panel.

Data indicated a 40.3% decrease in the incidence for HPV types 31 and 45 (95% CI, 13.9% to 59%) and a 43.6% decrease in cervical intraepithelial neoplasia 1-3/adenocarcinoma in situ (95% CI, 12.9% to 64.1%).

The researchers further observed a 25% reduction for HPV types 31, 33, 45, 52 and 58 (95% CI, 5% to 40.9%) and a 29.2% reduction in cervical intraepithelial neoplasia 1-3/adenocarcinoma in situ (95% CI, 8.3% to 45.5%). Reductions were most significant for HPV type 31.

Intention-to-treat analysis

Similar indications of cross-protection were confirmed in a companion study by Wheeler et al.

This intention-to-treat analysis examined 17,599 women who received one or more doses of the HPV vaccine or placebo. The researchers examined whether administration of the HPV vaccine reduced the incidence for HPV infection or cervical disease associated with HPV types 31, 33, 45, 52, and 58 for the duration of six months or longer.

Results indicated a reduction in these types of HPV by 17.7% (95% CI, 5.1% to 28.7%) and a reduction in the rate of cervical intraepithelial neoplasia 1-3 by 18.8% (95% CI, 7.4% to 28.9%). The combined incidence for infection with HPV types 31 and 45 was reduced by 31.6% (95% CI, 15.4% to 44.7%).

“These results complement the vaccine’s high prophylactic efficacy against disease associated with HPV 6, 11, 16 and 18 infections,” the researchers wrote. “Long-term monitoring of vaccinated populations will be needed to more fully ascertain the population-based impact and public health significance of these findings.”

In an accompanying editorial, Rolando Herrero, MD, of the Proyecto Epidemiológico Guanacaste, Fundación INCIENSA, San José, Costa Rica, wrote, “The cross protection reported in this issue of the Journal is definitely good news. However, 30% maximum protection against precursor lesions could reduce the burden of cervical cancer an additional 6%, compared with that afforded by the HPV-16/18 vaccine. This could represent ~30,000 cases worldwide but would still not afford protection against at least 25% of cancers, making the development of safe, effective, and low-cost polyvalent vaccines a major priority for both academia and industry, to ensure success in the fight against cervical cancer.” – by Jennifer Southall

For more information:

• Brown D. J Infect Dis.2009;199:926-935.
• Wheeler C. J Infect Dis.2009;199:936-944.

These are provocative data that suggest a potentially meaningful level of protection associated with HPV vaccination directed at specific viral types not included in the vaccine. Although further follow-up is required to more critically define both the magnitude and duration of cross-protection, the data provide hope that the actual level of benefit from vaccination will exceed that already documented by the impact of this strategy on the major oncogenic types [16 and 18].

– Maurie Markman, MD

Vice President For Clinical Research
University of Texas MD Anderson Cancer Center