No Emerging Safety Concerns With 9-Valent HPV Vaccine

By Will Boggs MD

November 21, 2019

NEW YORK (Reuters Health) - After three years of adverse-event surveillance and more than 28 million doses, the nine-valent human papillomavirus (9vHPV) vaccine shows no new or unexpected safety concerns, according to results from two studies.

"The results of this large safety study should reassure parents and patients; the 9vHPV vaccine is both safe and effective," Dr. James G. Donahue of the Marshfield Clinic Research Institute, in Marshfield, Wisconsin, told Reuters Health by email. "Hopefully, these results will help to diminish any hesitancy or concern about HPV vaccination."

The safety profile of the quadrivalent HPV vaccine (4vHPV) is well-established. In prelicensure clinical trials, the 9vHPV vaccine had a similar adverse-event profile. Since 2016, the 9vHPV vaccine is the only HPV vaccine distributed in the United States.

Dr. Donahue and colleagues conducted near real-time vaccine safety surveillance for 24 months after the 9vHPV vaccine became available (from October 2015 to October 2017) at six Vaccine Safety Datalink sites.

Among nearly 839,000 doses of 9vHPV administered during this interval, there were no signals for anaphylaxis, chronic inflammatory demyelinating polyneuropathy (CIDP), Guillain-Barre syndrome, seizure, stroke, or venous thromboembolism, the team reports in Pediatrics, online November 18.

Isolated statistical signals for pancreatitis, appendicitis, and allergic reactions were ultimately classified as false-positives, because cases were attributed to causes other than vaccination, showed no temporal clustering, or were observed in only a single analysis.

"When considering vaccination in terms of the benefits and risks, HPV vaccines have been shown to be very effective at preventing cancer-causing infections," Dr. Donahue said. "At the same time, there is a long track record that demonstrates their safety. This study, along with other recent studies, substantially adds to the safety profile of the HPV vaccines."

In the second study, also online November 18 in Pediatrics, Dr. Tom T. Shimabukuro of the U.S. Centers for Disease Control and Prevention (CDC), in Atlanta, and colleagues analyzed postlicensure surveillance reports of adverse events after 9vHPV to the Vaccine Adverse Event Reporting System (VAERS) from December 2014 through December 2017.

During this period, nearly 28 million doses of 9vHPV were distributed in the U.S., and VAERS received 7,244 U.S. reports of adverse events after 9vHPV. Overall, 97.4% of these reports were nonserious.

This translates into an overall crude reporting rate to VAERS of 259 reports per million 9vHPV doses distributed and seven serious reports per million 9vHPV distributed.

The crude reporting rate for syncope was 26 reports per million doses distributed, and the rates for all other conditions were less than one per million.

There were seven reports of death after 9vHPV, but five were hearsay reports that included no medical information or other documentation that could confirm a death has occurred, and in the other two cases, there was no documentation to suggest that 9vHPV caused or contributed to the deaths.

"There have been concerns among the public about particular conditions like primary ovarian insufficiency (POI), postural orthostatic tachycardia syndrome (POTS), complex regional pain syndrome (CRPS), and autoimmune disorders after HPV vaccines, including Gardasil 9," Dr. Shimabukuro said by email. "The findings from this analysis indicate that reports of these conditions are rare after Gardasil 9 and there are no unusual or unexpected reporting patterns that would suggest a link to Gardasil 9. Other analyses have demonstrated no association between HPV vaccines and these conditions. Together, these findings all indicate that HPV vaccines like Gardasil 9 are safe."

Dr. Nadja Alexandra Vielot of the University of North Carolina at Chapel Hill, who has studied the HPV vaccine, told Reuters Health by email, "These findings do not suggest an undue risk of severe adverse events following HPV vaccination and support the current CDC recommendations for routine and catch-up HPV vaccination. A provider's recommendation is one of the strongest predictors of HPV-vaccine acceptance, and providers can greatly influence vaccine uptake by informing parents that they recommend HPV vaccination and that their own children or grandchildren have been vaccinated."

"Vaccine providers should continuously monitor HPV-vaccine safety by reporting adverse events to VAERS," she said. "While rigorous studies continue to support the safety of HPV vaccines, pharmacovigilance is key to understanding the long-term safety of vaccines that we cannot necessarily discern from clinical trials. It is also important for maintaining trust in our scientific communities and health systems and making informed recommendations for vaccine policy."

Dr. Vielot, who was not involved the new studies, added, "HPV vaccination represents a unique opportunity to prevent the more than 300,000 cervical cancer deaths that occur each year across the globe. It is important to emphasize the burden of HPV-associated outcomes relative to vaccine safety risks to build support for this life-saving intervention."

Neither study had commercial funding.


Pediatrics 2019.