Human papillomavirus (HPV) is a common sexually transmitted pathogen. For some HPV types, infection can cause people to develop warts on different parts of the body. Some types of HPV are asymptomatic, but they can be passed from person to person. However, some of the most dangerous strains cause cancer. When HPV infection persists for a long time, the virus can damage the infected cells and transform them into cancer cells. Cancer driven by HPV is aggressive – cervical cancer caused by the virus is a leading cause of cancer-related deaths in developing countries – but these cancers are largely preventable.
Preventing long-term HPV infections is critical to prevent cervical cancer development. There are no treatments to eliminate HPV once a person is infected, but scientists have developed vaccines that effectively prevent infection and subsequent cancer cases. These vaccines prime the immune system prior to HPV infection by showing the immune system non-infectious parts of the HPV virus. When a real virus shows up, the immune system can act quickly and eliminate the HPV before serious infection starts. Initially, doctors and researchers recommended that people receive three doses of the HPV vaccine to be well-protected from the virus. A three dose regimen can be difficult to complete in resource poor countries or remote areas. As time went on, clinical trials found that two doses and then just one dose were just as effective at preventing disease, so the recommendations were changed to reflect this. Requiring fewer doses simplifies the vaccine regimen and alleviates the financial burden of vaccine programs on developing countries with the highest prevalence of HPV. Despite the benefits of fewer-dose vaccine regimens, whether they give the same long-term immune memory as 3-dose regimens is unclear. To address this question, Drs. Joseph Carter and Denise Galloway decided to measure HPV immune memory in patients that received two- and three-dose regimens.
Investigating a patient’s immune memory to any specific pathogen is challenging. At baseline, there are not many immune cells that exist to counteract HPV in a vaccinated subject’s body. Because they are so infrequent, it is impractical to count the cells persisting years after the initial 2 or 3 doses of HPV vaccine. Additionally, some immune cells only ramp up production in response to a pathogen, so it is impossible to tell how quickly these cells would intervene without the pathogen present. One way to measure immune memory years after vaccination could be to expose vaccinated participants to the HPV virus itself. This would cause the body to activate its immune memory to a level that researchers could measure. Because of ethical issues, this approach is impossible for clinical trials. Instead, the Galloway group used the next best thing: an extra dose of HPV vaccine.
This extra dose lets researchers measure the immune response to HPV. Participants in the trial received the extra dose of HPV vaccine anywhere from 3 to 10 years following their initial 2- or 3-dose regimen. After receiving the dose, the researchers measured HPV-specific immune memory cells and how quickly other immune cells intervened after the extra vaccine dose. Excitingly, the group found that there were no differences in any of the immune memory markers that they measured between participants receiving 2- or 3-dose regimens initially. This means that the simpler, more cost-effective 2-dose regimen is just as effective as the 3-dose regimen at preventing HPV infection or disease over a long period of time. This trial supports continuing the current 2-dose regimen in the future, a move that would continue to free up funds and alleviate stress on medical systems of countries with high HPV prevalence.
This work was supported by Merck Sharp & Dohme LLC.
Fred Hutch/University of Washington/Seattle Children's Cancer Consortium member Dr. Denise Galloway contributed to this work.
Carter JJ, Smith RA, Scherer EM, Skibinski DAG, Sankaranarayanan S, Luxembourg A, Kollmann T, Marty KD, Sadarangani M, Dobson S, Galloway DA. 2025. Term immune memory responses to human papillomavirus (HPV) vaccination following 2 versus 3 doses of HPV vaccine. Vaccine. 50:126817.
Kelsey Woodruff is a PhD candidate in the Termini Lab at Fred Hutch Cancer Center. She studies how acute myeloid leukemia cells remodel the sugars on their membranes to reprogram cancer cell signaling. Originally from Indiana, she holds a bachelor's degree in Biochemistry from Ball State University. Outside of lab, you can find her crocheting and enjoying the Seattle summers.
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