“There are two encouraging takeaways from our study,” said lead author Jessica Kahn, M.D., M.P.H., professor of pediatrics and the Dr. Ernest Baden Chair in Head and Neck Pathology at Einstein. “First, HPV vaccines work remarkably well in a real-world setting, even among women at high risk for HPV and who may not have received all vaccine doses. Second, we saw clear evidence of herd immunity, meaning when enough people are vaccinated, the vaccine indirectly protects unvaccinated people by reducing overall virus transmission. These results reinforce the potential of the HPV vaccine to prevent infection and, ultimately, eliminate cervical cancer globally.”
HPV is the most common sexually transmitted infection worldwide and is the primary cause of cervical cancer. HPV also causes other genital cancers as well as head and neck cancers in both women and men. According to the International Agency for Research on Cancer, HPV is responsible for more than 690,000 new cancer cases each year—about 4.5% of all cancers globally.
Testing a Vaccine’s Real-World Performance
While randomized clinical trials have shown that HPV vaccines confer strong protection from infection, “participants in those studies tended to be healthier and at lower risk for HPV than the general population, so they weren’t necessarily representative of the broader community,” said Dr. Kahn, who also serves as senior associate dean for clinical and translational research and director of the Harold and Muriel Block Institute for Clinical and Translational Research at Einstein and Montefiore. “That’s why we needed to evaluate how the vaccine works in real-world settings that included young women who were at relatively high risk for HPV and had different levels of vaccine uptake.”
The research team conducted six studies in Cincinnati of 2,335 adolescent and young adult women between 2006—just before the first HPV vaccine became available—and 2023. Participants ranged in age from 13 to 26 at enrollment. Many reported sexual behaviors that increased risk for HPV (79% had two or more male sexual partners) and 51% had a history of at least one sexually transmitted infection.
Participants were considered vaccinated if they had received at least one dose of any of the available HPV vaccines:
the 2-valent vaccine, which protects against HPV types 16 and 18 (responsible for over 70% of cervical cancers); the 4-valent vaccine, which protects against HPV types 16 and 18 and adds protection against types 6 and 11 (which cause about 90% of genital warts); and the current 9-valent vaccine, introduced in 2014, which in addition to HPV types 6, 11, 16 and 18, protects against five additional cancer-related HPV types (31, 33, 45, 52, and 58); the types targeted by this vaccine cause about 90% of cervical cancers. Over the 17-year study period, HPV vaccination rates rose from 0% to 82%. As vaccination coverage increased, the rates of HPV infection dropped dramatically among vaccinated participants:
Infections from HPV types covered by the 2-valent vaccine fell by 98.4% Infections from types covered by the 4-valent vaccine dropped by 94.2% Infections from types covered by the 9-valent vaccine declined by 75.7% “These outcomes show that HPV vaccines are highly effective outside of controlled trials and could dramatically reduce rates of cervical cancer and other HPV-caused cancers, including other genital cancers and head and neck cancers,” said Dr. Kahn.
“Our analysis of the data indicates that those reductions in infection rates were primarily due to the vaccine’s introduction and not because of changes in sexual behavior or other factors,” said Aislinn DeSieghardt, M.S., the paper’s first author and clinical research coordinator at Cincinnati Children’s Hospital Medical Center, Cincinnati, OH. “I also want to thank the all the young women who participated in the study, who have meaningfully contributed to this research that has the potential to save more lives.”
A Vaccine’s Benefits Extend to Unvaccinated Women
The researchers also found strong evidence of herd immunity. Among unvaccinated women:
Infections with HPV types covered by the 2-valent vaccine decreased by 71.6% Infections with HPV types covered by the 4-valent vaccine dropped by 75.8% Dr. Kahn noted that the high degree of herd immunity was likely related to robust vaccination rates and vaccination of boys as well as girls. While there wasn’t enough data yet to confirm herd protection from the more recently introduced 9-valent vaccine, the results are promising.
“In the U.S. and other countries with widespread HPV vaccination programs, cervical cancer rates are already declining,” Dr. Kahn said. “Yet in 42 countries, it remains the leading cause of cancer death among women. Globally, only 27% of girls have received at least one dose of this lifesaving vaccine – with coverage ranging from just 1% in the Eastern Mediterranean region to 68% in the Americas. By expanding uptake of this highly safe and effective vaccine, and ensuring access to screening and treatment, we can achieve one of the greatest public health victories of our time: the elimination of cervical cancer worldwide.”
The study is titled “Population-Level Effectiveness and Herd Protection 17 Years After Human Papillomavirus Vaccine Introduction.” Additional authors include Aislinn DeSieghardt and Lili Ding both at Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, Aaron Ermel and Darron Brown, both at Indiana University School of Medicine, Indianapolis, IN, Eduardo L. Franco at McGill University, Montreal, Canada, Casey Dagnall at Leidos Biomedical Research, Inc., Frederick, MD and National Cancer Institute, Rockville, MD, and Sem Yao at Western Reserve Hospital, Cuyahoga Falls, OH.
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About Albert Einstein College of Medicine
Albert Einstein College of Medicine is one of the nation’s premier centers for research, medical education and clinical investigation. During the 2024-25 academic year, Einstein is home to 712 M.D. students, 226 Ph.D. students, 112 students in the combined M.D./Ph.D. program, and approximately 250 postdoctoral research fellows. The College of Medicine has more than 2,000 full-time faculty members located on the main campus and at its clinical affiliates. In 2024, Einstein received more than $192 million in awards from the National Institutes of Health. This includes the funding of major research centers at Einstein in cancer, aging, intellectual development disorders, diabetes, clinical and translational research, liver disease, and AIDS. Other areas where the College of Medicine is concentrating its efforts include developmental brain research, neuroscience, cardiac disease, and initiatives to reduce and eliminate ethnic and racial health disparities. Its partnership with Montefiore, the University Hospital and academic medical center for Einstein, advances clinical and translational research to accelerate the pace at which new discoveries become the treatments and therapies that benefit patients. For more information, please visit einsteinmed.edu, follow us on Twitter, Facebook, Instagram, LinkedIn, and view us on YouTube.
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