The new human papillomavirus-16/18 vaccine does not appear to be effective in treating women with pre-existing viral infection and should be used for prevention only, according to an article in the August 15 issue of the Journal of the American Medical Association.

The vaccines were designed to prevent infection and subsequent development of cervical atypia and cancer. Some research has suggested that use of the vaccine could help clear the virus in women with pre-existing infection, according to background information in the article.

Allan Hildesheim, PhD, of the National Cancer Institute, Bethesda, MD, and colleagues conducted a study to address the question of whether women positive for viral DNA should be encouraged to receive vaccination to induce or accelerate clearance of viral infection.

The trial was conducted in two provinces of Costa Rica and included 2,189 women age 18 to 25 years who were positive for viral DNA. Participants were randomized to three doses of HPV-16/18 vaccine (1,088 patients) or a control hepatitis A vaccine (1,101 patients) over 6 months.

There was no evidence that human papillomavirus vaccination significantly altered rates of viral clearance. At the six-month visit, rates of clearance were 33.4 percent versus 31.6 percent for HPV-16/18 among participants who received active vaccine and control vaccine, respectively. At the 12-month visit, rates of clearance among participants in the active group and control group, were 48.8 percent versus 49.8 percent, respectively.

There was no evidence of vaccine effects with further analysis on selected study entry characteristics reflective of disease extent, including HPV-16/18 antibody results, cytologic results, and viral load.

Similarly, no evidence of vaccine effects was observed in analyses stratified by other study entry parameters thought to potentially influence clearance rates and vaccine efficacy including time since sexual initiation, oral contraceptive use, cigarette smoking, and concomitant infection with Chlamydia trachomatis or Neisseria gonorrhoeae.

“These findings have important clinical implications. For example, in countries where HPV DNA testing is incorporated in cervical cancer screening and prevention efforts, adult women who have abnormal Papanicolaou test results induced by HPV infection and/or who test positive for an oncogenic HPV type using the clinically available HC2 test might be interested in receiving the HPV vaccine to treat their existent infection,” the authors wrote. “… our results demonstrate that in women positive for HPV DNA, HPV-16/18 vaccination does not accelerate clearance of the virus and should not be used for purposes of treating prevalent infections.”

In an accompanying editorial, Lauri E. Markowitz, MD, of the Centers for Disease Control and Prevention, Atlanta, commented on the findings:

“What are the implications of these data and how do they bear on recommendations? The lack of therapeutic efficacy of the quadrivalent HPV vaccine was considered in deliberations by the Advisory Committee on Immunization Practices (ACIP). These data, along with data demonstrating the high likelihood of acquiring HPV infection soon after onset of sexual activity and data on sexual behavior in the United States, all contributed to recommendations for routine immunization at 11 to 12 years of age. Because the vaccine has no therapeutic efficacy, the greatest effect will be realized if the vaccine is administered before sexual debut, prior to exposure to HPV.”

“In making the recommendation for this age group, the ACIP also considered safety and immunogenicity data and programmatic issues. While there are safety and immunogenicity data in this age group through 18 months, as well as studies indicating good protection through 5 years after vaccination among older women, as for other new vaccines, data on long-term efficacy are limited. Data on longer-term efficacy will be important, particularly when targeting vaccination of 11- to 12-year-olds. Post-licensure safety monitoring, as done for all vaccines, will also be important.”