The final analysis of the PATRICIA study 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. The vaccine also shows cross-protective efficacy against other oncogenic (cancer-causing) HPV types closely related to HPV-16/18. Furthermore, it also shows efficacy in the cohorts relevant to universal mass vaccination and catch-up programmes. The findings are reported in an article online first and in an upcoming edition of The Lancet, written by Dr Jorma Paavonen, University of Helsinki, Finland, and colleagues.
The study looked at women aged 15-25 years who were vaccinated at months 0, 1, and 6. Analyses were done in the according-to-protocol cohort for efficacy (ATP-E, which included all women who were given 3 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; vaccine=8093, control=8069), the total vaccinated cohort (TVC, included all women who received at least one vaccine dose, regardless of their baseline HPV status; represents young sexually active population; vaccine=9319, control=9325), and TVC-naïve (no evidence of oncogenic HPV infection at baseline; represents women before sexual debut, vaccine=5822, control=5819). The primary endpoint was to assess vaccine against cervical intraepithelial neoplasia 2+ (CIN2+)—the precancerous lesions that can eventually lead to full-blown cervical cancer.
The mean follow-up was just under three years after the third dose. Vaccine efficacy against CIN2+ that was associated with HPV-16/18 was 93% in the primary analysis and 98% 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% in the TVC and 70% in the TVC-naïve. Corresponding values against CIN3+ (more serious precancer) were 33% in TVC and 87% in TVC-naïve, indicating the larger contribution of HPV-16/18 to The vaccine was also shown to be protective against other oncogenic (cancer causing) HPV types – most notably HPV-31 (related to HPV-16) and HPV-45 (related to HPV-18). Overall, the vaccine efficacy was calculated as between 37% and 54% against 12 non-vaccine oncogenic HPV types. Globally, around 70% of cervical cancer is estimated to be caused by HPV-16/18, with the remaining 30% caused by other oncogenic HPV types. Thus the cross-protective efficacy of this vaccine could represent 11—16%* additional protection against cervical cancer to that afforded by efficacy against HPV-16/18.
The authors say: "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 authors note the strengths and weaknesses of the study. The strengths include its duration and size, plus the diversity of the participants, which included a broadly representative group of women from North America, Latin America, Europe, and Asia-Pacific regions. However Africa and some other regions were not included, but trials have since begun in these areas. Limitations include that the true incidence rate for CIN2+ lesions from non-vaccine HPV types could have been underestimated, since it takes longer for such lesions to develop compared to lesions caused by HPV-16/18.
The authors conclude: "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 accompanying Comment, Dr Karin B. Michels, Harvard Medical School, Boston, USA and Dr Harald zur Hausen, German Cancer Research Centre, Heidelberg, Germany, say: "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 conclude: "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."
Dr Jorma Paavonen, University of Helsinki, Finland T) +358 50 4272060 E) Jorma.Paavonen@hus.fi
Dr Karin B. Michels, Harvard Medical School, Boston, USA (currently in Europe) T) +49 1622853785 E) kmichels@rics.bwh.harvard.edu
For full Article and Comment, see: http://press.thelancet.com/patriciafinal.pdf
Notes to editors: *the figure of 11—16% is found by calculating 37—54% of the 30% (30% of cervical cancers are from types of HPV other than 16 and 18)
Journal
The Lancet