A new analysis of the clinical trials of HPV vaccines to prevent cervical cancer raises doubts about the vaccines’ effectiveness. The analysis, published by the Journal of the Royal Society of Medicine, assessed 12 published phase 2 and 3 randomized controlled efficacy trials of the HPV vaccines Cervarix and Gardasil. Carried out by researchers at Newcastle University and Queen Mary University, the analysis revealed many methodological problems in the design of the phase 2 and 3 efficacy trials, leading to uncertainty regarding understanding the effectiveness of HPV vaccination. The researchers found that the trials were not designed to detect cervical cancer, which takes decades to develop. Women in the trials were followed up for 6 years or less, apart from one trial extension to just under 9 years. While the researchers found evidence that vaccination prevents low grade abnormal cell changes, they said this is not clinically important because no treatment is given. Trials may have overestimated efficacy by combining high-grade cervical disease with low-grade cervical changes that occur more frequently but often resolve spontaneously without progressing. The researchers found insufficient data to clearly conclude that HPV vaccine prevents the higher-grade abnormal cell changes that can eventually develop into cervical cancer. Calling for women to still attend regular cervical screening, co-author of the study, Professor Allyson Pollock, of Newcastle University, said: “We have good evidence that cervical screening significantly reduces the risk of cervical cancer in women regardless of whether they have been vaccinated. “As with changes to the information given on breast cancer screening program, it is important that parents and young people are told about the uncertainties in the information leaflets and advice given by GPs. People need to be aware that given these uncertainties it is important that even if you have the vaccine, women attend cervical screening, which we know can prevent the development of cervical cancer.” Lead researcher Dr Claire Rees, of Queen Mary University, said: “Abnormal cell changes are likely to have been overdiagnosed in the trials because cervical cytology was conducted at 6-12 months rather than at the normal screening interval of 36 months. This means that the trials may have overestimated the efficacy of the vaccine as some of the lesions would have regressed spontaneously.” The researchers also found that the trial populations had limited relevance and validity for real world settings. The women in the trials were older than the target population. Professor Pollock who is director of the Newcastle University Centre for Regulatory Science added: “The process would be improved by identifying and reducing the uncertainties generated by trial design for example avoiding use of composite surrogate measures with different natural histories, prevalence and rates of regression and progression. Also developing long-term phase 4 and observational studies and non-industry funded trials to avoid conflicts of interest.“ Source
