Numbers game: Researchers explore whether fewer than 3 doses of HPV vaccine are effective.

Abstract

CancerVolume 122, Issue 1 p. 11-12 CancerScopeFree Access Numbers game: Researchers explore whether fewer than 3 doses of HPV vaccine are effective First published: 17 December 2015 https://doi.org/10.1002/cncr.29815Citations: 1AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Vaccinating adolescents for human papillomavirus (HPV), the most common sexually transmitted virus in the United States, continues to present challenges both nationally and globally, and now researchers are questioning whether all 3 doses of the vaccine are necessary. New evidence indicates that 1 or 2 doses of the vaccine may be as effective as 3; however, those same researchers do not want parents or adolescents to think that they need only 2 doses. “The vaccines have not been approved in the United States for fewer than 3 doses, and the last thing we need is to have a pause in our attempts to get coverage with all 3,” says Cosette Wheeler, PhD, regents' professor in the departments of pathology and gynecology at the University of New Mexico Health Sciences Center in Albuquerque. “We don't have the data we need to make a change in the recommendations.” Dr. Wheeler, who has spent more than 20 years researching the molecular epidemiology of HPV in cervical precancer and cancer and was involved with early research on HPV vaccines, was one of the co-authors of a study recently published in Lancet Oncology.1 The study involved a combined analysis of 2 independent studies of the bivalent HPV-16/18 AS04- adjuvanted vaccine (Cervarix) and showed that 3 doses, 2 doses, and 1 dose of the vaccine protected equally against infection with the HPV types included in the vaccine 4 years after vaccination. The results were pooled from the National Cancer Institute–sponsored Costa Rica Vaccine Trial and the GlaxoSmithKline Biologicals–sponsored Papilloma Trial Against Cancer in Young Adults (PATRICIA). In both trials, participants were randomly assigned to receive 3 doses of the HPV-16/18 vaccine or a control vaccine. Investigators decided to conduct the pooled analysis after they had seen results from the Costa Rican trial showing that although approximately 20% of the participants received fewer than 3 doses, most often because of pregnancy, the efficacy was the same, regardless of the number of doses received. They decided to pool the data with results from the PATRICIA trial to confirm their findings and also to address other research questions. The pooled findings included 611 participants who received 2 doses and 292 who received just 1 dose of the vaccine. Another key finding was that participants who received 2 doses of the vaccine 6 months apart showed evidence of partial crossprotection against other HPV types not included in the vaccine; however, women who received 1 dose or 2 doses just 1 month apart showed no evidence of cross-protection. (Current US guidelines state that the vaccines should be given in 3 doses over a 6-month period.) “These results are very helpful,” says Electra Paskett, PhD, professor of cancer research in the Division of Cancer Prevention and Control at Ohio State University. “They give more ammunition for researchers to study the efficacy of 3 versus 2 versus 1 dose and the amount of time that should occur between doses.” Elise Kohn, MD, head of gynecologic cancer therapeutics at the National Cancer Institute, says, “The authors are to be congratulated for getting the per case data and examining the depth of the question to provide detailed and provocative findings to further support the potential value of this vaccine in less than 3 doses.” Other Vaccines This study focused only on Cervarix, which is the 2-valent HPV vaccine manufactured by GlaxoSmithKline. It specifically targets the HPV-16 and HPV-18 strains, which cause 75% of cervical cancers. The trial did not look at the efficacy of different numbers of doses of the 2 other vaccines currently approved by the Food and Drug Administration (FDA) for use in the United States: Gardasil, approved in 2006, which prevents infection by 4 strains of HPV (6, 11, 16, and 18) and Gardasil 9, approved in 2014, which protects against the 4 strains in the previous version of Gardasil as well as strains 31, 33, 45, 52, and 58. Both are produced by Merck. Although Cervarix was approved by the FDA in 2009, it was approved to be administered only to females aged 10 to 25 years. Meanwhile, Gardasil was approved by the FDA for use in males and females aged 9 to 26 years. For those reasons and probably because it was approved earlier, Gardasil is currently the main HPV vaccine used in the United States, Dr. Wheeler says. “We need more data on the vaccines we use in this country to make these extrapolations,” Dr. Wheeler says. “When we began these studies, we didn't know how all the [vaccine approval] decisions in the US would be made.” The Cervarix vaccine is used in other countries, and a number of other countries have already switched to administering 2 doses of the HPV vaccine because of evidence showing that the number of antibody titers in patients appears the same when 2 doses are compared with 3 doses. However, that evidence is not sufficient to change guidelines in the United States. A randomized trial comparing different dose levels would be needed for that, the researchers say. At the same time, the Gardasil and Cervarix vaccines should be compared with each other in terms of safety and effectiveness, Dr. Wheeler says, because they are based on different adjuvants that trigger different types of immune responses. More data in that area are expected to become available soon. GlaxoSmithKline is conducting a 3-year randomized clinical trial to evaluate the immunogenicity and safety of Cervarix administered according to a 2-dose schedule versus Gardasil (4-valent vaccine) administered according to a 2-dose schedule or the standard 3-dose schedule. Is 1 Dose Enough? “We all believe we can give 2 doses, but whether we can give just 1 remains unknown,” Dr. Wheeler adds. The benefit of using 1 dose would be increased uptake of the HPV vaccine not just in the United States but worldwide, researchers note. In the United States, for example, only 40% of female adolescents (aged 13 to 17 years) are estimated to have received all 3 doses of the HPV vaccine in 2014 according to the Centers for Disease Control and Prevention (CDC). The goal of the CDC for herd immunity is 80% coverage, Dr. Paskett says. Most crucial, however, is HPV vaccination in the developing world, where 80% to 85% of the annual cervical cancer deaths occur. The vaccine is not widely available in those countries, and few cervical cancer screening programs exist. A report by the Kaiser Family Foundation notes that in 2013, Merck and GlaxoSmithKline were awarded United Nations Children's Fund contracts to provide Gardasil and Cervarix vaccines to people in developing countries at significantly reduced prices. As a result, HPV vaccination is expected to be supported in 28 countries by the end of 2017. At the same time, if it is ultimately shown that only 1 dose of the vaccine is needed, the evidence would significantly improve vaccine coverage in developing countries by eliminating the infrastructural, logistical, and cost challenges of providing more than 1 dose in those countries, researchers say. “With 1 dose [effectiveness], if we could vaccinate every woman under age 15 in the world, over time you could eradicate cervical cancer,” Dr. Wheeler says. “There are not many examples of that. If it takes 3 doses, we probably can't have that impact.” Investigators note that a variety of other issues related to HPV vaccines will have to be addressed with additional research. They include assessing these vaccines at different dose levels in boys as well as girls, monitoring the duration of protection afforded by fewer doses, and learning the most effective intervals between doses. With 1 dose [effectiveness], if we could vaccinate every woman under age 15 in the world, over time you could eradicate cervical cancer. —Cosette Wheeler, PhD References 1 Kreimer AR, Struyf F, Del Rosario-Raymundo MR, et al. Efficacy of fewer than three doses of an HPV-16/18 AS04-adjuvanted vaccine: combined analysis of data from the Costa Rica Vaccine and PATRICIA trials. Lancet Oncol. 2015; 16: 775– 786. CrossrefCASPubMedWeb of Science®Google Scholar Citing Literature Volume122, Issue1January 1, 2016Pages 11-12 This article also appears in:CancerScope Archive 2014-2019 ReferencesRelatedInformation