Women aged 24-45 years not already infected with the human papilloma virus (HPV) can be protected by the HPV vaccine, concludes an Article to be published in The Lancet, written by Dr Nubia Muñoz, National Institute of Cancer, Bogotá, Colombia, and colleagues.
Changes in sexual behaviour during the past 30 years, characterised by rising age at first marriage and an increase in divorce rates, have led to more widespread premarital intercourse and acquisition of new sexual partners around middle-age, respectively. Thus there is a potential for older women to benefit from vaccination against the HPV virus, which is transmitted through sexual intercourse and can lead to cervical cancer or other cervical disease. In this randomised trial, women with no history of cervical disease or cancer or genital warts, caused by HPV types 6, 11, 16 and 18, were vaccinated with either the quadrivalent HPV vaccine, which aims to protect women from all four vaccine types, or placebo.
A total of 1,911 women received the vaccine and 1,908 were given placebo, at day 1 and months 2 and 6. There were two endpoints assessed— the first was 6 months or more duration of infection and cervical and external genital disease due to HPV6, 11, 16, 18; and the second the same as above but due to HPV 16 and 18 only. The mean follow-up time was 2.2 years (with more data to be reported at the end of the four-year trial). Specific populations among the women were analysed.
The per-protocol population consisted of 1,615 women given the vaccine and 1,607 placebo. These women all tested negative for the relevant vaccine HPV type on day 1 and also up to month seven. They also had to have had all three vaccine doses within one year, and have one or more follow-up visits after month seven. The researchers found that, among these women, four cases of infection or disease occurred in the vaccine group compared to 41 in the placebo group – meaning the vaccine showed 91% efficacy against all four virus strains.
Looking at HPV 16 and 18 only, four cases occurred in the placebo group compared with 23 in the placebo group, giving a vaccine efficacy of 83%. The intention-to-treat populations included women who not been completely vaccinated and/or had pre-existing HPV infection. When these women were included in the analysis, vaccine efficacy against all four HPV types was lower at 31%, while that specifically against types HPV 16 and 18 was 24%.
The authors say: “Lower effectiveness (about 30%) detected in the mixed population (susceptible women and those who have already acquired HPV infection or HPV-associated disease) suggests that the public health effect of vaccinating women aged 25–45 years will be smaller than that recorded after vaccinating susceptible adolescents. This notion will be assessed in future cost–benefit analyses.”
While the study had a dual endpoint, the authors note that most of the women that reached the endpoint had infections, rather than cervical/genital disease. Thus the high vaccine efficacy in the intention-to-treat population was mostly as a result of efficacy against infection. The authors say: “Maximum effect from prophylactic HPV vaccination programmes will be achieved in women who are susceptible to infection and disease related to vaccine HPV types (those not previously exposed). Notably, most adult women enrolled in the current study remained susceptible to vaccine HPV types at entry. Almost all women enrolled were susceptible to three or four vaccine HPV types, and about a third were positive to HPV 6, 11, 16, or 18 at baseline by serological or DNA testing; therefore about two-thirds were susceptible to all four vaccine HPV types. Most women who were HPV positive were positive to only one HPV type, meaning that the quadrivalent HPV vaccine could still potentially benefit these women via protection against vaccine HPV types with which they are not infected with.”
They conclude: “The quadrivalent HPV vaccine is efficacious in women aged 24–45 years not infected with the relevant HPV types at enrolment.”