Quadrivalent HPV Vaccine Appears Safe, but Skeptics Remain

October 3, 2012 — Among females, routine administration of quadrivalent human papillomavirus (HPV) vaccine was associated with no new safety concerns, according to findings of a large retrospective study.

Nicola P. Klein, MD, PhD, from the Kaiser Permanente Vaccine Study Center in Oakland, California, and colleagues reported their findings online October 1 in the Archives of Pediatric and Adolescent Medicine.

According to the researchers, HPV causes approximately a half million new cases of cancer annually, mainly among women in developing countries. In 2006, the US Food and Drug Administration (FDA) approved quadrivalent (types 6, 11, 16, and 18) HPV vaccine, recombinant (Gardasil, Merck and Co. Inc), which raises immunity to protect against a range of diseases attributed to multiple types of HPV.

The vaccine is indicated for females aged 9 to 26 years for protection against genital warts and gynecologic cancers. More recently, the vaccine was approved for administration to males and females 9 to 26 years of age for the prevention of anal cancer.

Prelicensure clinical trials indicated that the quadrivalent vaccine is highly immunogenic and safe in females. The current study was undertaken as a postlicensure commitment to the FDA and an initial licensure trial in females for the European Medicines Agency.

The researchers evaluated medical records from a cohort of female patients 9 to 26 years of age who received the quadrivalent vaccine between August 2006 and March 2008. The retrospective study included a total of 189,629 patients who received at least 1 dose (any-dose population), and a subset of 44,001 patients who received all 3 recommended doses within 12 months (3-dose population).

The safety study monitored postvaccination emergency department visits and hospitalization event codes found in electronic medical records and categorized the codes according to groups defined by the Healthcare Cost and Utilization Project.

The results indicate that vaccination may be associated with syncope on the day of vaccination (odds ratio [OR], 6.0; 95% confidence interval [CI], 3.9 - 9.2) and skin infections occurring 1 to 14 days after immunization (OR, 1.8; 95% CI, 1.3 - 2.4). No major adverse effects were associated with the vaccine.

"Our findings are consistent with a previous study that noted an elevated reporting rate for syncope to the passive Vaccine Adverse Event Reporting System following [administration of quadrivalent vaccine]," the researchers conclude.

They add that their results "contrast with the recent Vaccine Safety Datalink study, which did not detect an increase in syncope after [administration of quadrivalent vaccine] when compared with rates following health care visits for other vaccinations,” the investigators write. “The difference may be that, within this age group, injections rather than [the vaccine] specifically could be related to syncope."

"Future studies will be needed to develop a better understanding of the relationship between injections and/or vaccinations and syncope among adolescents and young adults," they add.

Other research groups are also evaluating the safety of the HPV vaccine. Lucija Tomljenovic, PhD, from the Department of Ophthalmology and Visual Sciences at the University of British Columbia in Vancouver, Canada, and colleagues recently carried out a systematic review of HPV vaccine pre- and postlicensure trials to assess the evidence of their effectiveness and safety. "We found that HPV vaccine clinical trials design, and data interpretation of both efficacy and safety outcomes, were largely inadequate," she told Medscape Medical News.

"Given this, the widespread optimism regarding HPV vaccine's long-term benefits appears to rest on a number of unproven assumptions, which are at odd with factual evidence, and significant misinterpretation of available data," she said. "For example, the claim that HPV vaccination will result in approximately 70% reduction of cervical cancers is made despite the fact that the clinical trials data have not demonstrated to date that the vaccines have actually prevented a single case of cervical cancer."

"Further reduction of cervical cancers might be best achieved by optimizing cervical screening and targeting other factors of the disease rather than by the reliance on vaccines," she added.

The study was sponsored by Merck & Co Inc. Dr. Klein receives research support from Merck & Co Inc, GlaxoSmithKline, Pfizer, Novartis, and sanofipasteur for unrelated studies. Other authors received research funding from Merck & Co Inc (for another study related to HPV4), served as an unpaid consultant to Merck & Co Inc, an received research funding from Merck & Co Inc, Amgen, and Pfizer (for unrelated studies). Two authors are employees of Merck & Co Inc. Dr. Tomljenovic has disclosed no relevant financial relationships.

Arch Pediatr Adolesc Med. Published online October 1, 2012. Abstract