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Background In 2009 the World Health Organisation (WHO) recommended the inclusion of routine human papilloma virus (HPV) vaccines in national immunisation programmes to reduce the global burden of cervical cancer. The aim of this review was to critically appraise the evidence of efficacy of HPV vaccines in the studies used by the WHO in support of its recommendation.
Methods The efficacy-publications were retrieved from the WHO Immunisation, Vaccines and Biologicals webpage and each publication was appraised against the Critical Appraisal Skills Programme (CASP) framework and compared with WHO Strategic Group of Experts’ GRADE-evaluation of evidence with special focus on outcome measures, length of follow-up and general applicability of the results.
Results The WHO based its decision on three phase III trials and two phase II trials. The age range of enrolled females (15–26 years) was not compatible with the recommended vaccine age (9–13 years). All five studies used surrogate endpoints, namely cervical intraepithelial neoplasia (CIN) stadia I, II and III and Adenocarcinoma in situ (AIS). The direct effect of HPV vaccines on the natural history of cervical cancer was not assessed. Gardasil’s® efficacy for the prevention of cervical lesions associated with all known HPV types was very low and not statistically significant for CIN 3 and AIS. Gardasil® and Cervarix® proved efficacious only when all endpoints were grouped and when a subgroup analysis was undertaken of HPV 16 and or 18 naïve women. Individual endpoints were measured in two trials only and the number of cases was small and confidence intervals were wide. Grouping endpoints is problematic because of different rates of progression and regression especially for CIN 1, which is also the most prevalent cervical lesion. The percentage of cervical lesions associated with HPV types 16 and or 18 was lower than the 70% reported in medical literature. Maximum follow up was 6.4 years with only two trials examining participants for more than 4 years. General applicability of results is not clear due to lack of data on recruitment and composition of country samples.
Conclusion WHO’s recommendation to include routine HPV vaccination in national immunisation programmes is based on weak evidence namely surrogate outcome measures, which are very likely to regress spontaneously. Data on long-term efficacy are lacking.