A single dose of the bivalent human papillomavirus (HPV) vaccine (Cervarix) offers a similar level of protection against the HPV-16/18 infections - which cause about 70% of cervical cancers - as current two- and three-dose schedules, according to data from two large phase 3 trials.

Worldwide, cervical cancer is the fourth most common cancer in women. The bivalent vaccine targets HPV types 16 and 18 that are responsible for about 70% of cervical cancers. The HPV-16/18 vaccine was initially approved to be given in three doses over 6 months, but many countries are moving to a two-dose schedule in adolescents.

This new combined analysis of two independent trials strengthens previous findings from the NCI Costa Rica HPV Vaccine Trial (CVT) which reported that young women who received three, two, or one dose of the bivalent vaccine were equally protected against infection with HPV-16/18 for at least 4 years after vaccination.

“Our findings question the number of HPV vaccine doses truly needed to protect the majority of women against cervical cancer, and suggest that a one-dose schedule should be further evaluated. If one 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,” says co-lead author Dr Aimée Kreimer from the National Cancer Institute (NCI), National Institutes of Health. 

Due to the lack of efficacy data on fewer than three doses, the researchers conducted a post-hoc analysis combining data from the CVT that included 7466 healthy women aged 18–25 years old and the Papilloma Trial against Cancer in Young Adults (PATRICIA) trial in 18644 healthy women aged 15–25 years from Asia-Pacific, Europe, Latin America, and North America. Women in both trials were randomly assigned to receive the HPV-16/18 vaccine or a control (hepatitis A) vaccine, given in three doses: at enrollment, 1 month, and 6 months. However, some of the women received fewer than three doses, mainly because their vaccination was discontinued due to pregnancy.

After excluding women with no follow up or who had cervical HPV infection at enrolment, the investigators calculated vaccine efficacy against HPV infection after three doses (22,327 women), two doses (1,185), and one dose (543). Women were followed on average for 4 years.

High vaccine efficacy was seen against incident HPV-16/18 infections regardless of the number of doses received. This result was also observed in a subgroup of women with no sign of HPV infection either before or at the time of first vaccination, suggesting that these results are relevant to sexually-naïve girls in the recommended age range for HPV vaccination (ie, 11–12 years).

In further analyses, partial protection against other HPV types not included in the vaccine formulation was seen among women who received two doses 6 months apart, similar to that reported for three doses.

The authors caution that more data are needed before policy guidelines can be changed. Dr Cosette Wheeler, co-lead author from the University of New Mexico Health Sciences Center, Albuquerque, USA, explains, “Using existing data, we showed that a single dose of the bivalent HPV vaccine may be sufficient to substantially reduce cervical cancer incidence. Yet, a new randomised study will be needed to confirm these findings and move the field forward. Additionally, duration of protection from a single dose must be demonstrated beyond 4 years.”

CVT was funded by the US National Cancer Institute intramural research program, National Institutes of Health Office of Research on Women’s Health, and Ministry of Health of Costa Rica; GlaxoSmithKline Biologicals SA funded the PATRICIA trial.