HPV 16/18 vaccine ineffective against preexisting infection

To cure an established infection, researchers would need to generate a different kind of immune response.

Researchers have demonstrated there is no therapeutic benefit with the bivalent human papillomavirus 16/18 L1 protein virus-like particle vaccine for human papillomavirus types 16/18 in young women with preexisting infection.

“Our study provides strong evidence that there is little, if any, therapeutic benefit from the vaccine in the population we studied. Furthermore, we see no reason to believe that there is a benefit of the vaccine elsewhere because the biological effect of vaccination among already infected women is not expected to vary by population,” the researchers wrote in the study. Results were published in the Journal of the American Medical Association.

“These results were not surprising because the mechanism of action of the vaccine is through antibodies that block infection at the time of exposure. To cure an established infection, researchers need to generate a different kind of immune response, the so-called cell-mediated immunity, which, in addition, has to be directed to components of the virus that are different from the ones targeted by the vaccine,” Rolando Herrero, MD, an epidemiologist from Guanacaste, Costa Rica, told Infectious Disease News.

This study includes a subset of patients from an ongoing study of more than 7,000 women from Costa Rica.

Costa Rican study

Prior to enrollment, participants were required to fulfill the following requirements:

• Aged between 18 and 25 years.
• Able to speak and understand Spanish.
• Were in good general health.
• Willing to provide consent.

The study population consisted of 2,189 women from Costa Rica who tested positive for HPV at enrollment. The researchers gave all participants who were sexually active a pelvic exam, and blood samples were collected from all participants to test for HPV infection at enrollment.

Participants were randomly assigned to receive three doses of either the bivalent HPV 16/18 L1 protein virus-like particle AS04 vaccine (Cervarix, GlaxoSmithKline) (n=1,088) or a control hepatitis A vaccine (n=1,101). Participants were vaccinated at baseline, one month after the first dose and six months after the second dose.

At the six-month visit, all sexually active women were asked to self-collect a cervicovaginal specimen with a swab for further HPV DNA testing.

The participants were then required to attend a follow-up visit one year after enrollment, at which time all sexually active women were given a second pelvic exam.

HPV was determined with a molecular hybridization assay by using chemiluminescence with HPV RNA probes at enrollment.

Enrollment specimens and specimens collected at the six-month and 12-month visits were also tested for HPV by PCR.

Clearance rates for HPV 16/18

At the six-month visit, clearance rates for HPV 16/18 infection among the HPV-vaccinated group were 33.4% compared with 31.6% in the control group; at the 12-month visit, clearance rates among the vaccinated group were 48.8% compared with 49.8% in the control group.

“There was no evidence of a therapeutic effect for other oncogenic or nononcogenic HPV categories among the participants who received all vaccine doses with single infections or among participants stratified by entry variables such as HPV 16/18 serology, cytologic results or HPV DNA viral load,” the researchers wrote.

Rates of viral clearance among the control group at the six-month visit were higher in various other HPV types when compared with HPV 16 (ranging from 44.6% to 61.1%); clearance rates at the 12-month visit ranged from 59.2% to 78.1%.

According to the researchers, these results indicated the rates of viral clearance for a 12-month period are not influenced by vaccination.

“Vaccine efficacy for preventing persistent infection of HPV 16/18 at six months was 2.5% and was –2% at 12-months. These findings are consistent with data from trials of the quadrivalent HPV 6/11/16/18 vaccine. These data reinforce that women with abnormal pap smear results or those with positive HPV results should be managed according to current guidelines and that HPV vaccine does not have a role in treatment,” Lauri E. Markowitz, MD, of the CDC, wrote in an accompanying editorial.

“We want physicians to get the clear message that this vaccine will not help women who have an infection or lesion caused by HPV 16 or 18,” Herrero said. – by Jennifer Southall

For more information:

• Hildesheim A, Herrero R, Wacholder S, et al. Effect of human papillomavirus 16/18 L1 virus-like particle vaccine among young women with preexisting infection. JAMA. 2007;298:743-753.
• Markowitz L. Editorial: HPV vaccines — prophylactic, not therapeutic. JAMA. 2007;298:805-806.