The findings of the PATRICIA study are reported in an article Online First and in a future edition of The Lancet. It shows that the HPV-16/18 AS04-adjuvanted vaccine (GlaxoSmithKline) has high efficacy against the precancerous cervical lesions that can eventually lead to cervical cancer. There is confirmation that the vaccine also shows cross-protective efficacy against other oncogenic (that cause cancer) Human Papillomavirus (HPV) types closely related to HPV-16/18. In addition, it also shows efficacy in the cohorts relevant to universal mass vaccination and catch-up programs. The article is written by Dr Jorma Paavonen, of the University of Helsinki, Finland, and collaborators.

The women included in the study were aged 15 to 25 years and were vaccinated at months 0, 1, and 6. Analyses were done in the according-to-protocol cohort for efficacy. The ATP-E included all women who were given three vaccine doses, had normal pap smears or pap smears showing mild abnormalities at baseline, complied with the protocol and were evaluable for the primary endpoint. There were 8,093 in the vaccine group, 8,069 in the control group. The total vaccinated cohort (TVC) included all women who received at least one vaccine dose, regardless of their baseline HPV status. It represents the young sexually active population. There were 9,319 in the vaccine group, 9,325 in the control group. The TVC-naïve included women showing no evidence of oncogenic HPV infection at baseline. It represents women before they become sexually active. There were 5,822 in the vaccine group, 5,819 in the control group. The primary endpoint was to assess vaccine against cervical intraepithelial neoplasia 2+ (CIN2+) which are the precancerous lesions that can eventually lead to full-blown cervical cancer.

The average monitoring was a little less than three years after the third dose. Vaccine efficacy was 93 percent against CIN2+ that was associated with HPV-16/18 in the primary analysis. Vaccine efficacy was 98 percent in an analysis in which causality to HPV type was assigned in lesions infected with multiple oncogenic types. Vaccine efficacy against CIN2+ irrespective of HPV type detected in lesions was 30 percent in the TVC and 70 percent in the TVC-naïve. The matching values against CIN3+ which is a more serious pre-cancer were 33 percent in TVC and 87 percent in TVC-naïve. This indicates a larger contribution of HPV-16/18. The vaccine also proved to be protective against other cancer causing HPV types, particularly HPV-31 which is related to HPV-16 and HPV-45 which is related to HPV-18. In general, the vaccine efficacy was estimated between 37 percent and 54 percent against twelve non-vaccine oncogenic HPV types. As a result, the cross-protective efficacy of this vaccine could represent 11 to 16 percent additional protection against cervical cancer to that afforded by efficacy against HPV-16/18. This percentage is established by calculating 37 to 54 percent of the 30 percent of cervical cancers that are from types of HPV other than 16 and 18.

The authors explain: “The reduction in the number of lesions in the TVC and TVC-naïve was accompanied by a significant proportional reduction in the numbers of colposcopy referrals and cervical excision procedures. Reduction in the number of cervical excision procedures might be accompanied by a reduction in the numbers of preterm births and other adverse pregnancy outcomes because these outcomes have been shown to be associated with the treatment of CIN.”

The researchers comment on the strengths and weaknesses of the study. The duration and size of the study are the strong points, as well as the diversity of the participants from North America, Latin America, Europe, and Asia-Pacific regions. Some other regions like Africa were not included, but trials are now in progress in these areas. The boundaries of the research include that the accurate rate of incidence for CIN2+ lesions from non-vaccine HPV types could have been underestimated. This possible miscalculation results from the fact that it takes longer for such lesions to develop compared to lesions caused by HPV-16/18.

The authors write in conclusion: “The HPV-16/18 AS04-adjvanted vaccine showed high efficacy against CIN2+ that was associated with HPV-16/18 and non-vaccine oncogenic HPV types, and substantial overall effect in cohorts that are relevant to universal mass vaccination and catch-up programmes.”

“Although the importance of continued tests for pap or HPV in vaccinated and unvaccinated women must be emphasised, HPV vaccination has the potential to substantially reduce the incidence of cervical cancer and precancer, and the numbers of colposcopy referrals and cervical excision procedures.”

In an associated observation, Dr Karin B. Michels, of theHarvard Medical School, Boston, USA and Dr Harald zur Hausen,of the German Cancer Research Centre, Heidelberg, Germany, write: “Currently, the targets for HPV vaccination are girls and young women aged 11-26 years prior to sexual debut. While good utilization of the program will reduce cervical cancer incidence in a couple of decades, this subgroup of the population at risk is too small to limit the spread of the virus. The only efficient way to stop the virus is to also vaccinate the other half of the sexually active population: boys and men.”

They write in closing: “Women have shouldered responsibility for contraception since its inception. The goal to eradicate sexually transmitted carcinogenic viruses can be jointly carried by women and men and could be accomplished within a few decades.”

“Efficacy of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by oncogenic HPV types (PATRICIA): final analysis of a double-blind, randomised study in young women”
J Paavonen, P Naud, J Salmerón, C M Wheeler, S-N Chow, D Apter, H Kitchener, X Castellsague, J C Teixeira, S R Skinner, J Hedrick, U Jaisamrarn, G Limson, S Garland, A Szarewski, B Romanowski, F Y Aoki, T F Schwarz, W A J Poppe, F X Bosch, D Jenkins, K Hardt, T Zahaf, D Descamps, F Struyf, M Lehtinen, G Dubin, for the HPV PATRICIA Study Group
DOI: 10.1016/S0140-6736(09)61248-4

Written by Stephanie Brunner (B.A.)