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Single Dose of Human Papillomavirus Vaccine May Prevent Most Cervical Cancer

Just 1 dose of the Cervarix human papillomavirus (HPV) vaccine was able to protect 85% of young women against cancer-causing HPV types 16 and 18, suggesting that it could prevent a majority of cervical cancer cases, including in settings were administration of the full 3-dose series is difficult, according to an analysis of data from 2 large trials published in the June 9 edition of Lancet Oncology.

HPV is among the most common sexually transmitted infections, with most people acquiring one or more of the approximately 100 genotypes soon after they become sexually active. HPV can trigger abnormal cell changes including anal-genital warts and anal, cervical, and other genital cancers.

Until recently, 2 vaccines were FDA-approved for HPV prevention: GlaxoSmithKline's Cervarix, which protects against HPV types 16 and 18 (the primary causes of anal and cervical cancer), and Gardasil, which protects against HPV 16 and 18 as well as 6 and 11 (which cause genital warts). This past December the FDA approved a new "9-valent" version of Gardasil that also protects against the less common cancer-causing types 31, 33, 45, 52, and 58.

U.S. public health officials recommend HPV vaccination for young women and men age 9 to 26. In the U.S. the approved schedule is 3 doses administered within 6 months. But the need for multiple doses can hinder adherence and many people do not receive the full series. This can be especially problematic in resource-limited areas where people do not receive frequent health care. Last year the World Health Organization released guidelinescalling for girls to receive 2 rather than 3 HPV vaccine doses, based on research showing that the 2-dose schedule is equally effective. A 1-dose vaccine would improve convenience and reduce cost even further.

Aimée Kreimer from the U.S. National Cancer Instituteand fellow investigators with the Costa Rica Vaccine Trial and PATRICIA study groups did a post-hoc analysis of pooled data from a pair of Phase 3 randomized controlled trials to evaluate the efficacy of the bivalent HPV 16/18 vaccineby number of doses, and to explore whether it offers some protection against HPV types not included in the vaccine.

Together the 2 trials enrolled more than 26,000 young women (age 15-25 years) in Asia, Europe, Latin America, and North America. Participants were randomly assigned to receive 3 doses of either the HPV-16/18 AS04-adjuvanted vaccine or a control hepatitis A vaccine. Doses were scheduled for enrollment, 1 month later, and 6 months later, but not everyone actually completed the full series (mainly due to pregnancy).

This combined analysis looked at outcomes after an average 4 years of follow-up and included 22,327 women who received 3 doses, 1185 who received 2 doses, and 543 who received 1 dose. The primary study endpoint was one-time detection of the first new infection with HPV 16 or 18.

Vaccine efficacy against incident HPV 16/18 was found to be 77.0% for 3 doses, 76.0% for 2 doses, and 85.7% for 1 dose. In addition, efficacy against HPV types 31/33/45 was 59.7% with 3 doses, 37.7% with 2 doses, and 36.6% with 1 dose.

"4 years after vaccination of women aged 15-25 years, 1 and 2 doses of the HPV-16/18 vaccine seem to protect against cervical HPV-16/18 infections, similar to the protection provided by the 3-dose schedule," the study authors concluded. "2 doses separated by 6 months additionally provided some cross-protection. These data argue for a direct assessment of 1-dose efficacy of the HPV-16/18 vaccine."

Given that HPV types 16 and 18 cause approximately 70% of all cervical cancer cases, these results suggest that a single vaccine dose may be able to prevent most cervical cancer in young women. Further research is needed to see whether 1 dose offers similar protection against anal cancer in young women and men.

"Our findings question the number of HPV vaccine doses truly needed to protect the majority of women against cervical cancer, and suggest that a 1-dose schedule should be further evaluated," Kreimer stated in a Lancet media release. "If 1 dose is sufficient, it could reduce vaccination and administration costs as well as improve uptake. This is especially important in less developed regions of the world where more than 80% of cervical cancer cases occur."

"If HPV vaccines could be delivered as one dose, while retaining their efficacy against the most oncogenic HPV types 16 and 18, the global burden of cervical cancer would substantially decrease," said Julia Brotherton from the Victorian Cytology Service Registries in Melbourne. "Data from studies have shown how effective 1-vaccine dose campaigns can be in even the most resource-poor settings...This campaign would not need ongoing resources to sustain annual vaccination programs against HPV in settings with many pressing health priorities and small numbers of health-care workers."

6/17/15

Reference

AR Kreimer, F Struyf, MR Del Rosario-Raymundo, 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 Oncology S1470-2045(15)00047-9. June 9, 2015 (Epub ahead of print).

Other Source

The Lancet. The Lancet Oncology: Two large trials provide further evidence that one dose of HPV vaccine could prevent the majority of cervical cancers. Media release. June 8, 2015.