Two doses of HPV vaccine may be as effective as three

This study is the first to show preliminary evidence that a two-dose HPV vaccination regimen may provide protection as effective as that of the three-dose regimen. The findings are encouraging, but very preliminary, Dr. Jennifer Kahn and Dr. David L. Bernstein wrote in an editorial.

An effective two-dose regimen is a goal worthy of pursuing because many barriers prevent the fullest utilization of the HPV vaccine, wrote Dr. Kahn and Dr. Bernstein.

"These barriers include the high cost of vaccination and the many challenges associated with administration of a three-dose vaccine, especially given the lack of infrastructure for adolescent vaccination programs in many countries ... A two-dose series could lead to a substantial increase in the number of girls completing the vaccine series for the same cost, ensuring that greater numbers are protected."

The short-term equivalent immunogenicity demonstrated in the study indicates the potential for developing such a regimen and thus, reaching many more girls in their early adolescence – the time when they mount the most robust immune response. "However, and most important, antibody responses for HPV-18 at month 24 and HPV-6 at month 36 were significantly higher for girls who received three doses. This comparison of girls 9-13 years of age receiving two vs. three doses is important clinically, because girls in this age group are targeted for vaccination."

However, an amended regimen should also be tested in girls aged 13 and older, because, although younger girls are the primary vaccination target, many older girls are actually vaccinated.

"Depending on the results of these studies, clinical efficacy studies should be conducted to ensure that two doses of the ... vaccine are sufficient to prevent incident and persistent HPV infection, precancers (not only cervical but also anal, vaginal, and vulvar precancers), and anogenital warts, because the immunologic response that correlates with protection against HPV is unknown."

Males represent a big question mark in this entire equation, the authors noted.

"Studies of immunologic responses in men will also be important, because there is now a recommendation for men to receive the quadrivalent vaccine in the United States. If a two-dose series were immunogenic in men, cost-effectiveness estimates could become more favorable with respect to male vaccination, which in turn could alter vaccine recommendations for men. Also, if a two-dose schedule is recommended, consideration must be given to the possibility that a month 0 and 6 schedule may delay protection compared to a month 0, 1 to 2, and 6 schedule."

If these future studies do confirm a durable immune response from a two-dose schedule, the global impact could be significant, Dr. Kahn and Dr. Bernstein concluded.

"The potential to further reduce morbidity and mortality due to HPV-related cancers would be especially significant in less developed regions of the world, where the cost of vaccination and implementation of adolescent vaccination programs present significant barriers, but where primary prevention strategies are most urgently needed."

Dr. Kahn is an adolescent medicine expert in the department of pediatrics at Cincinnati Children’s Hospital Medical Center, and Dr. Bernstein is an infectious diseases expert in the department of pediatrics at the medical center. Dr. Kahn is on a grant review committee administered by the Society for Adolescent Health and Medicine (funded by Merck), which is funding projects designed to improve adolescent vaccination rates, and is cochair on clinical trials of the HPV vaccine in HIV-infected women and men funded by the National Institutes of Health, with Merck providing the vaccines. Dr. Bernstein receives speaking fees and royalties from GlaxoSmithKline for sales of a rotavirus vaccine.