2 HPV vaccine doses found as good as 3

Two doses of vaccine — and possibly a single dose — may offer as much protection against infection with cancer-causing forms of human papillomavirus as the standard three-dose series, according to results from a large study in Costa Rica.

The finding, the first clinical evidence suggesting that two doses or even one dose may be as effective as three, holds promise for women in resource-poor countries and may have important implications for relatively rich countries, such as the United States, where vaccine uptake has been difficult to achieve, and where less than a third of girls receiving HPV vaccine are estimated to get  a full three doses.

In the study, 7,466 women aged 18-25 years, most of them sexually active, were randomized to receive three doses of the HPV16/18 vaccine Carvarix, or a hepatitis A control vaccine, as part of an ongoing phase III, randomized controlled trial.

All women in the study were supposed to receive three doses of either HPV vaccine or control, however, some of the women received fewer doses, largely because of pregnancy and referral to colposcopy.

The fact that many women did not complete the series allowed researchers,  led by an epidemiologist of the US National Cancer Institute, to conduct an analysis comparing the efficacy of fewer than three doses of this HPV vaccine with the standard regimen  in preventing newly detected persistent HPV16 and HPV18 infections. Persistent infections were defined as evident in visits 10 or more months apart; all women in the study were seen annually during 4 years of follow-up.

After excluding women who had no follow-up or who were HPV16 and HPV18 positive at enrollment, 5,967 women who received three doses of HPV or hepatitis vaccine (2,957 received HPV or 50%), 802 who received one dose (196 HPV or  51%) were entered into analysis, for a total of 7,153.

Vaccine efficacy was 80.9% for three doses of HPV vaccine (25 and 133 1-year persistent HPV16/18 HPV infections in the HPV and control arms, respectively), 84.1% for two doses (3 and 17 infections), and 100% for one dose (0 and 10 infections). Persistent HPV16 or HPV18 infections were found to be unrelated to dosage of the control vaccine.

Noted that although the study used data from a large randomized trial, their analysis was not randomized. However, “the attack rates of new infections were essentially equal among women who received one, two and three doses of the control vaccine. Equal attack rates in the control arm suggested that risks of infection were the same regardless of number of doses received. Furthermore, pregnancy, the most common reason that women received a reduced number of doses, was unrelated to vaccine assignment,” and therefore unlikely to bias the findings.

They acknowledged that while the benefit appeared to be the same for two and three doses, the duration of that benefit beyond 4 years was uncertain, and required further research.

Additionally, researchers cautioned that their findings from the bivalent vaccine trial could not be extrapolated to the widely used quadrivalent HPV vaccine Gardasil, which is also administered in a three-dose series. Nor could they be considered relevant to populations with a greater incidence of comorbidities, particularly disease affecting the immune system.