Are we ready for a single-dose HPV vaccine?

A new paper in the journal Lancet Oncology evaluates outcomes after vaccination with Cervarix, which is the HPV vaccine that is effective against the 2 most oncogenic (cancer-causing) strains: HPV 16 and 18. The paper is actually a compilation of results from two studies of Cervarix among women ages 15-25 and now has four years of follow-up data on more than 26,000 women.

While the intent of both studies was to give all women three doses, not everyone received all three. (It was often a pregnancy that lead to the dropout.) The outcomes of women who received one and two doses were compared with the women who received all three. When the data was analyzed, one dose of Cervarix was equally effective at protecting against infection with HPV 16 and 18 as two and three doses. Antibody levels were lower with one dose versus two or three but still much higher at four years than would occur after a “natural” HPV infection. When two doses were given six months apart, there was some cross-protection against infection with HPV 31/33/45 (other cancer-causing strains not in the vaccine).

Both HPV vaccines (Cervarix and Gardasil) were developed with a prime-prime-boost schedule, which means doses at 1,2, and 6 months. These vaccines are highly effective at producing antibodies, and there is some data to suggest two doses (the 2nd dose at six months) are as good as the three. The U.K. has already moved to a 2 dose regimen for both vaccines.

These results cannot be translated to Gardasil, the other HPV vaccine. This is because there are one of two things giving the immune system such a good kick from a single dose of Cervarix — the virus-like particles (VPL, which are recognized by the immune system and stimulate an antibody response) or the adjuvant (the ingredient that helps trigger the immune response). VLP vaccines are very good at stimulating the immune system and typically produce high levels of antibodies that last. If the favorable response to a single dose of Cervarix is due to the VPL, then a single dose could potentially be enough for Gardasil. However, if the response is due to the adjuvant, then this will be unique to Cervarix as it has a completely different adjuvant than Cervarix.

This isn’t enough data to move to a single-dose of Cervarix just yet. In a press release from Lancet Oncology Dr. Cosette Wheeler, co-lead author, indicated that a randomized study will be needed to confirm the findings. Also, according to Dr. Wheeler duration of protection from the single dose for more than four years will need to be confirmed.

The public health implications of going to a single dose would be huge. This vaccine protects against the two viruses that cause about 70 percent of cervical cancers, and a single dose would reduce costs dramatically as well as simplify administration. If a single dose proves as effective in a prospective trial, this could be a real game changer, especially for women in third world countries where cervical cancer screening programs are virtually non-existent. However, even in industrialized countries the cost savings would be huge, and it is reasonable the think that vaccination rates might rise if only a single dose was needed.