Cochrane review on the efficacy and safety of HPV vaccines by Sciensano authors

Sciensano’s conflict of interest policy

In May 2018, the Cochrane Database of Systematic Reviews¹ published a meta-analysis on the safety and efficacy of HPV vaccines. The first three authors are researchers from the Cancer Centre of Sciensano. The review concluded that HPV vaccines offer good protection against the HPV types in the vaccine and also against precancerous cervical lesions associated with these HPV types. 

The efficacy of the vaccines is excellent among girls and young women aged under 26 years if they do not carry the relevant HPV types. Efficacy reduces with age and also when considering the population as a whole, because part of the population has already come into contact with HPV. HPV is mainly sexually transmitted. Persistent infection with high-risk types cause almost all cervical cancers and a significant proportion of cancers of the anus, vulva, vagina, penis and throat. 

The Cochrane review also concluded that HPV vaccines are responsible for local (pain, swelling, erythema) and mild general side-effects which usually disappear after a few days. No significant association could be established between HPV vaccines and serious side-effects.

In reactions it was stated that the Cochrane review was incomplete, biased, did not demonstrate evidence of protection against cancer and that the authors were influenced by the industry. The Cochrane Review primarily addressed data published in scientific journals. Not all HPV vaccination studies have been published, but results can sometimes be found in “grey literature” (trial registers). 

However, additional analyses carried out by the teams of the Editor-in-Chief of Cochrane and Sciensano demonstrated that the results of published and unpublished trials are very similar and therefore found that the criticisms were not justified².  The Cochrane Funding Arbiters conducted an assessment before and after the publication of the Cochrane Review and rejected the criticism of a conflict of interest and found that the review adhered to Cochrane’s strict conflict of interest policy.

Sciensano has expertise recognised throughout the world in the area of prevention and treatment of cervical cancer. In this context, collaboration with the industry that produces tests or vaccines is difficult to avoid. Scientific studies involving collaboration with the industry are, however, only conducted within a strict legal framework that guarantees the independence of the studies. 

The VALGENT studies are an example of public-private collaboration. They are set up by the Cancer Centre of Sciensano and contribute to the evaluation of HPV tests³. VALGENT is a protocol for the evaluation of HPV tests, developed by experts in HPV virology and by epidemiologists specialised in the methodology of test evaluation. This protocol was published in a recognised scientific journal after peer review. VALGENT is a model of public-private scientific research that provides relevant and valuable information and this model can also be applied to testing for other diseases.

VALGENT is set up by researchers and is not an initiative from the industry that produces HPV tests. The contracts are signed by the Directions of the institutions concerned (recognised virology laboratories and Sciensano), after approval of the respective legal services. The firms must bear the costs of laboratory testing and statistical analyses. These costs are paid to the scientific institution and not to the scientists concerned who thus have no financial benefit from the collaboration with the VALGENT network. The publication of the results relating to the validation of an HPV test is submitted to the producer concerned. The latter can propose corrections of errors but it cannot prevent a publication on the pretext that the test does not fulfill the validation criteria.

Transparency and scientific rigour guarantee the added value for public health. The list of HPV tests, validated via VALGENT, is internationally recognised and used to design new programs for early detection of cervical cancer.

References

1. Arbyn M, Xu L, Simoens C, Martin-Hirsch PP. Prophylactic vaccination against human papillomaviruses to prevent cervical cancer and its precursors. Cochrane Database Syst Rev 2018;5: CD009069.
2. Tovey D, Soares-Weiser K, Cochrane’s Editor in Chief responds to a BMJ Evidence-Based Medicine article criticizing the Cochrane Review of HPV vaccines. 2018.
3. Arbyn M, Depuydt C, Benoy I, Bogers,J.; Cuschieri,K.; Schmitt,M.; Pawlita,M.; Geraets,D.; Heard,I.; Gheit,T.; Tommasino,M.; Poljak,M.; Bonde,J.; Quint,W. VALGENT: a protocol for clinical validation of human papillomavirus assays. J Clin Virol 2016;76 (Suppl 1): S14-S21.