Human Papillomavirus (HPV) Vaccines as an Option for Preventing Cervical Malignancies: (How) Effective and Safe?

Abstract

We carried out a systematic review of HPV vaccine pre- and post-licensure trials to assess the evidence of their effectiveness and safety. We find that HPV vaccine clinical trials design, and data interpretation of both efficacy and safety outcomes, were largely inadequate. Additionally, we note evidence of selective reporting of results from clinical trials (i.e., exclusion of vaccine efficacy figures related to study subgroups in which efficacy might be lower or even negative from peer-reviewed publications). Given this, the widespread optimism regarding HPV vaccines long-term benefits appears to rest on a number of unproven assumptions (or such which are at odd with factual evidence) and significant misinterpretation of available data. For example, the claim that HPV vaccination will result in approximately 70% reduction of cervical cancers is made despite the fact that the clinical trials data have not demonstrated to date that the vaccines have actually prevented a single case of cervical cancer (let alone cervical cancer death), nor that the current overly optimistic surrogate marker-based extrapolations are justified. Likewise, the notion that HPV vaccines have an impressive safety profile is only supported by highly flawed design of safety trials and is contrary to accumulating evidence from vaccine safety surveillance databases and case reports which continue to link HPV vaccination to serious adverse outcomes (including death and permanent disabilities). We thus conclude that further reduction of cervical cancers might be best achieved by optimizing cervical screening (which carries no such risks) and targeting other factors of the disease rather than by the reliance on vaccines with questionable efficacy and safety profiles.

HPV vaccines and cancer prevention, science versus activism

“…Instead, what the clinical trials have shown is that HPV vaccines can prevent some of the pre-cancerous CIN 2/3 lesions associated with HPV-16 and HPV-18 infection, a large fraction of which would spontaneously resolve regardless of the vaccination status [2-4]. For example, in adolescent women aged 13 to 24 years, 38% of CIN 2 resolve after one year, 63% after two and 68% after three years [5].…”

“…[7] CIN 2 is the least reproducible of all histopathologic diagnoses and may in part reflect sampling error. While CIN 3 is a more reliable marker for cancer progression than CIN 2, the use of this marker is not without caveats [2,10]. …”

“…Indeed, the optimistic assumption that HPV vaccination (even if proven effective against cervical cancer as claimed), will result in 70% reduction of cervical cancers appears to be largely based on premature, exaggerated and invalid surrogate marker-based extrapolations [2,11]. Crucially, these assumptions failed to take into account several important real-world factors such as:…”

HPV vaccine: Why the rush?

“…Adverse reactions as serious as permanent disability or even death (139 deaths so far) [2] are likely to result from the aluminium adjuvant that accumulates in the central nervous system. [3] The goal -the prevention of cervical cancer -remains to be proven. Finally, the two existing vaccines 'protect' only against two out of ten or more high-risk HPV types.…”

“…Finally, the two existing vaccines 'protect' only against two out of ten or more high-risk HPV types. [3][4][5][6][7] Ever since gaining Food and Drug Administration approval in 2006, Merck has been heavily criticised in the USA for their overly aggressive lobbying campaigns and marketing strategies. [4] Further, the vast majority of publications on the topic have been authored by Merck or GlaxoSmithKline (GSK) employees, or researchers employed by or funded by these companies.…”