HPV Vaccine and Others Safe, Effective When Coadministered

Norra MacReady

January 16, 2014

Adding a human papillomavirus (HPV) vaccine to a child's other immunizations does not affect the safety or efficacy of any of the vaccines involved, a new study suggests.

In a systematic review of 9 studies, "[n]oninferiority of immune response and an acceptable safety profile were demonstrated when HPV vaccine was coadministered with other vaccines" in all but one of the investigations, Alinea S. Noronha, MD, from the Division of STD Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, and coauthors write in an article published online January 8 in Vaccine.

Coadministration improves a child's chances of getting all the vaccines he or she needs, they explain. "Optimizing clinical visit time by administration of multiple recommended vaccinations at office visits could improve vaccine coverage by eliminating missed opportunities."

Dr. Noronha and colleagues reviewed 1 double-blind and 8 open-label, randomized controlled trials of multiple vaccine coadministration published between 2008 and 2012. The quadrivalent HPV vaccine was used in 4 studies, and the bivalent vaccine in 5 studies. There were between 144 and 1871 participants in each study, ranging in age from 9 through 25 years. Coadministered vaccines included the meningococcal conjugate vaccine in 3 studies; the tetanus, diphtheria, acellular pertussis (Tdap) vaccine in 3 studies; the combined Tdap and polio vaccines in 2 studies; the hepatitis B vaccine in 2 studies; and the combined hepatitis A and B vaccines in 1 study.

Each study assessed immune response by measuring seroconversion or seroprotection, defined as the percentage of participants with antibody concentration or titers above a predetermined threshold. Vaccine noninferiority was determined by comparing geometric mean titers, geometric mean antibody concentration, or seroconversion rates with those of the control group. "Reviewed studies reported noninferior antibody responses against diphtheria, tetanus, hepatitis B, hepatitis A, polio and meningococcal antigens in coadministered groups when compared to individually vaccinated groups," the authors write.

Noninferiority of the immune response to pertussis was observed in all but one of the studies that tested for it. In that study, coadministration of the Tdap, meningococcal conjugate vaccine, and HPV vaccines resulted in failure to meet the noninferiority criteria established for the geometric mean concentration ratios of antipertussis pertactin and antifilamentous hemagglutinin antibodies, defined as the ratio of the antibody concentration of the coadministered group compared with that of the control group. Both are antipertussis antibodies. Some evidence suggests that the meningococcal rather than the HPV vaccine may be responsible for this finding, the authors say. Its clinical significance is unclear.

Safety was determined by having the study participants report symptoms 30 minutes after vaccine administration and at various intervals thereafter. The most commonly reported symptoms were adverse events at the injection sites, such as pain, swelling, and bruising. The incidence of adverse events was inconsistent, but overall there were few significant differences between the control and coadministered groups.

Although the authors did not review studies of all the coadministered vaccines, "available data suggests [the] HPV vaccine is safe and effective when administered with other vaccines," they conclude.

"Given [that] HPV vaccine coverage is below target levels in the United States," these findings may provide an extra dose of reassurance that vaccine coadministration is wise.

The authors have disclosed no relevant financial relationships.

Vaccine. Published online January 8, 2014. Abstract

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