By Helen Petousis Harris 03/03/2017 11


A new study used the World health Organization’s global database of reports of adverse events associated with the use of a medicine (VigiBase), including vaccines, to look at reporting patterns after HPV vaccine.

The cases in VigiBase are collected for 125 member states, including NZ, who participate in the WHOs International Drug Monitoring Programme. The data from all the member states are pooled together. The pooled database is extensive (it is really bigly 14.468 million reports as of yesterday, although the paper mentions that in 2010 it was 10.3 million.

The ‘cases’ in the database are reports of events that have occurred either in association with, or following, the use or administration of a medicine. These cases may or may not have been caused by the medicine.

What did this study do?

The authors wanted to test a novel computer algorithm to see if they could group cases reporting similar symptoms such as dizziness or skin rash. They used HPV vaccine reports from around the world to do this (VigiBase). This is potentially a very cool tool.

It is important to note that the cases the publication based its research on are derived from data extracted from reports from member states. These reports are identified using a dictionary of possible events terms from case summaries submitted. The level of clinical detail available for each report is not necessarily always comprehensive. In other words there is a certain degree of garbage in garbage out because the data going in is highly variable (imagine all the different doctors, nurses and members of the public from all the different countries filling in the report forms, in different languages!). Making a diagnosis based on this data is near impossible. The authors note this themselves

The greatest limitation of this study is the lack of information on many of the reports in VigiBase. Missing data means that it may be difficult to make a clinical judgment regarding case relevancy.

What did the study find?

The study found that the algorithm could indeed place symptoms into clusters. Unfortunately it is not clear from the paper how successful the methodology was at separating different conditions into different clusters.

Did the study find that HPV vaccine causes CRPS or POTS?

No. There are three reasons the study did not determine this. One is because that was not the research question being asked in the first place; two, the study was not designed to answer that question; and three, it is an accepted fact that databases such as VigiBase cannot be used in this way (causality assessment).

The authors themselves state in their conclusion that they cannot use this analysis to draw any conclusions regarding a causal relationship between the HPV vaccine and reported adverse events.

A causal association with the HPV vaccine remains uncertain

It is common to identify safety signals with vaccines, most of them are dismissed after further investigation. This signal has already been investigated further in NZ and EU and no evidence has been found to show that HPV vaccines cause this syndromes [click here for the NZ Medicines Adverse Reaction Committee minutes].

But the study found reports of CRPS and POTS.

Yes, the study identified these conditions. However, it is also essential to note:

  1. These conditions occur every year in every country, particularly in adolescent girls, so some cases will inevitably occur after vaccination by chance and find their way to this reporting system. This is especially relevant where there is high uptake of the vaccine in this population group.
  2. Interestingly, Japan and Denmark have contributed a significant number of reports. These countries have also experienced extensive media coverage and lobbying on the topic of these specific conditions. Even more interesting is that when cases from Japan and Denmark are removed from the analysis for serious headache+dizziness+fatigue or syncope the significance disappears (this result is found in the supplementary material).
  3. Anti-vaccination groups have been actively collecting cases of these conditions. I am making an assumption these will be reported to the adverse event reporting system.
  4. There is no description of the timing of onset of these cases from the point of vaccination. If there is a biologically plausible causal association between vaccine and onset of symptoms there should be a consistent time between vaccination and development of symptoms. This was not addressed in this study which is another reason it cannot be used to infer causality.

Summary

This study describes a novel methodology in the earliest stages of development that has great potential benefit. However, as yet its true ability to identify meaningful clusters to inform further research has not been established. At best the authors have identified clusters of symptom constellations observed in association with HPV vaccination. However, as with other publications of case reports of related symptoms, further and more in-depth scientific investigation of these associations (signals?) is required to establish whether these associations are causal and if so, the mechanisms by which they occur.

I think these are the main messages about this study. It did not find that HPV vaccine causes anything. Also, in my opinion, the authors have extended their claims about the study and made statements that are unsupported by their methods and results. I think they should have left it as a methods paper and considered a title that better reflects the study.

Additional links on the safety of Gardasil from NZs Medicines Safety Authority, MedSafe:

 

 


11 Responses to “WHO VigiBase study does not find HPV vaccine unsafe.”

  • Over 72,000 adverse reports.Vigiacesss/Uppsala WHO.. we must be looking at different information and those are only the ones reported…excludes the parents who are fobbed off and told that Gardasil is safe, so could not possibly be responsible for their child’s deteriorating health. It does not include those who may have followed through and filled out adverse events reports, but were not even offered these at A&E departments after repeated visits and it does not include adverse events experienced by those, who do not even know they can fill out such forms or the existence of the forms. You are not an expert in ‘systemic’ effects regarding Gardasil are you? What you fail to mention, which is of paramount importance, is the
    use of active components, as so called placebos in the clinical trials. This impacts on the conclusions stated, regarding
    causation…proven/unproven. Placebos used in the Gardasil clinical trials, were the same components used in the vaccine itself; the exact same components, which you recently attempted to describe in another of your blogs, being trialled against the same vaccine;components that were made up of the same adjuvant and excipients used in Gardasil. ( Amorphous Aluminium Hydroxyphosphate Sulphate, which was also the adjuvant itself, L-Histidine, Poly Sorbate 80,and Sodium Borate) Now you may not accept that these are detrimental when injected into humans, but these have been studied by qualified individuals, who have provided their findings for consideration and at the same time, urged further scientific evaluations. One such individual, has studied aluminium, including its metabolic pathways in humans, for over 30 years, so I personally would rather listen to those
    people, than those who deny the effects on the human body when ‘injected’ with such components, or those who show no interest in the Precautionary Principle. You are deluding yourself in denying vaccine injuries, especially when so many are not even being reported globally, less than 10% and some serious cases, as is known, are removed from the public databases. I personally know of one such individual whose case was removed related to suspected Gardasil vaccine injury and no action has been taken to investigate this. This happened in NZ. So much for transparency. The adverse events reported in the clinical trials, were serious in nature and are the same outcomes currently being reported globally, but ignored in your world, as just a coincidence, temporally associated, anecdotal… I just don’t buy it…and I find it really offensive when I read how you described recently, those who speak out of their experiences and adverse events, as ‘fantasy,’ words to that effect… you get the meaning.. the word ‘fantasy’ leaves me in no doubt that you have a total lack of insight. Living with a
    vaccine injured child post Gardasil is hardly a fantasy.. .and this attitude is insulting and demonstrates your disconnect to
    the reality of what is taking place in NZ and around the World. It is becoming known by many families, many clinicians
    and a number of immunologists and other specialists in their fields internationally, that there are problems with the
    Gardasil HPV vaccines. You can deny this all you like, it does not change the truth. Access to information that health
    professionals have, are the very same sources, the public have access to and data from clinical trials are available to literate,
    intelligent and inquisitive individuals, who are undaunted by denialists and those who seem disinterested, in scrutinizing
    the undone science, omissions of evaluations, skewed adverse outcomes and absence of long term safety studies. Not
    concerned that spontaneous abortions were increased within the first 30 days of vaccination with Gardasil? Not concerned
    about the increased reporting of autoimmune disorders? Not concerned that the data was extrapolated from the much older
    participants, who were on the pill and then conclusions drawn, that these same outcomes would apply to the much younger
    prepubertal and peripubertal participants in the trials? No Ovarian studies done in the clinical trials, to determine effects
    on fertility or reproductive disorders as a result of this vaccine. Yet you are so certain there are no problems? Not
    concerned that a potent vasodilator is an excipient in the vaccine.. what effect might this have? Lives are being affected by
    the lack of due diligence to these concerns. It is high time that health professionals started to read the trial data, so that they
    are better placed to have a collaborative discussion, with those who expect them to have the ability to assist with the process of Informed Consent, relating to risk vs benefit. How can health professionals be expected to do this and to actually
    provide full disclosure of risks and any benefits? Let’s be honest the data is not even up to date. The saline placebo was not
    actually just a saline placebo .. and the non alum placebo… well you know what was in that. ..Any health professionals I
    have spoken to, or any people I know who have spoken to health professionals, have very quickly realised how little that
    most doctors know about this vaccine and the clinical trials. This is not good enough. You dismiss those in Europe who have
    concerns regarding Gardasil, as if these people have gone away… do keep up… this is not the case…and it is not over yet..it is ongoing..as are other investigations..Perhaps you would do best to be aware of what is going on globally and how so
    many people are not in agreement with your blog opinions. Your mantra is tiresome. Your targets are falling. People just want informed consent. If this is too much to ask, then you have a problem. Where there is risk there must be choice and let’s be frank, it looks as if someone has dropped the ball big time, because there are some risks that cannot be denied and really need to be evaluated and others revisited for further scrutiny. So, please stop trying to marginalise those who are exercising their democratic and human rights and trying to be responsible citizens. We will decide what is best for our families, once we have all the information required to make an informed decision.

    informed consent. If this is too much to ask, then you have a problem. Where there is risk there must be choice. and let’s be frank, it looks as if someone has dropped the ball, because there are some risks that cannot be denied and really need to be evaluated and others revisited for further scrutiny. So, please stop trying to marginalise those who are exercising their
    democratic and human rights and trying to be responsible citizens.

      • You obviously have not read the clinical trial data, or read the letter sent by the Australian TGA, explaining the misinformation in the trials, regarding the placebos. I have a NZ FOIA response which states what is in the non alum placebo. All the evidence I need and confirmed by others as well. CT scan showing cerebral oedema us pretty convincing to me. Plenty of evidence out there…truth is coming …

    • Fiona the tirade is unhelpful. Ashton and Jeremy raise important points, as they have in the past. In refusing to engage in the actual issue and dogmatically repeating your mantra you are guilty of dispersing an extensive list of fallacies about vaccines, both factual and logical. Indeed some say that this sort of behaviour in the social media and web space is called trolling.

      The first fallacy that springs to mind is that of Special Pleading, or moving the goal posts and making up exception when your claim is shown to be false. For example, why do you not acknowledge the vast amount of evidence from large epidemiological studies investigating the safety of HPV vaccine? Anecdote – the use of personal experience, putting forward isolated examples instead of scientific evidence. For example holding up case studies as evidence for causality. Strawman arguments are where you misrepresent someone’s position or argument. I could go on and list more, particularly ad hominem attacks…

      When we ask you to present evidence for your argument we mean scientific evidence. Science based evidence requires the scientific method to be applied to a question. Fiona I challenge you to pose a question about HPV then go about trying to answer it using a rigorous empirical approach.

  • You keep raising the placebo issue like it makes a difference. Aluminium adjuvant safety is well established.

    And stop saying I obviously have or have not done things. What you consider compelling evidence may not compel me.

    I’ve read a lot, and it supports the safety of Gardasil.

  • Good morning Fiona. I’m not going to go into detail on your large post above, but I note a couple of things that intrigue me and that call for your clarification, or further information.

    1 – “You are deluding yourself in denying vaccine injuries, especially when so many are not even being reported globally, less than 10%…” If they are unreported, on what basis can you make this claim? Is this an extrapolation from other studies on medical non-reporting, or some other statistical approach, or a re you claiming that there is a large separate database of reports that does not correspond with the recognised adverse report databases?

    2 – ” and some serious cases, as is known, are removed from the public databases. I personally know of one such individual whose case was removed related to suspected Gardasil vaccine injury and no action has been taken to investigate this” You’ve previously raised this claim but have not provided any information to allow independent confirmation of the specific case, or of the general claim. Are you able to do so now?

  • I agree with you Jeremy, Ashton and Helen.
    Might I suggest Fiona, that you structure your “argument” in a readable fashion, and finish your points instead of using endless questions (many seeming rhetorical) and switching subject all the time as Helen has pointed out. Stay on track with the current blog at hand. You havent provided a coherent and scientifically robust argument against the article that can be properly responded too. Helen has described why we cannot use the WHO VigiBase study to make bold conclusions about the safety of Gardisal as you seem to think. So please stay on that topic and respond to what she has said, as well as reading the other comments and responding in a suitable fashion to those.

    Although my questions and thoughts are mainly covered by Jeremy and Ashton, I have a query.
    You start by saying “Over 72,000 adverse reports”. Ok. Where are you going with this? Even the study states (as Helen also mentioned) reports are not neccesarily related to the vaccine and are all reports within the time frame. As well as Helen mentioning the effects Denmark and Japan have had on the study. I dont think we are reading a different study, its a matter of understanding how the data is gathered and the strengths and limitations of it, which you dont seem to be taking on.

    You then went on to ask if “You are not an expert in ‘systemic’ effects regarding Gardasil are you?”
    Well I pose this question to you. What gives you the authority to be making the claims you do that go against many experts who have given many years to their work and found HPV to be safe?

    • Mikio, You quote from one of the presentations at the meeting in Denmark.

      Need for review of the world-wide data, comparative data on background incidences etc.

      But you do not complete that 2015 story, which was to refer the world-wide review to the EMA. The EMA conducted a world-wide review and we all know their conclusions.

      You have also neglected to mention the conclusions from that meeting. https://www.uantwerpen.be/images/uantwerpen/container39248/files/2016%2011%20Copenhagen/Cope%20801%20Meeting%20conclusions%20.pdf I think it is fair to say the conclusions indicate Denmark more concerned about the impact of anti-vaccination movement and communication challenges that the actual safety of the vaccine.

      Presenting multiple case studies or laboratory studies does not indicate there is a problem with the vaccine. Case studies are hypothesis generating only. The fact remains that with all the global vaccine safety surveillance so far there is no epidemiological evidence that the HPV vaccine causes these conditions. Answer me this: If the vaccine caused these events then why can we not find it when we look in large populations and compare vaccinated with unvaccinated?

      • Dear Helen, thank you for your comments:

        Do you know the clinical oncologist’s analysis to the critics expressed by EMA? I agree with his analysis, and introduce some of the contents that are important to know.

        An analysis of the critics expressed by EMA against 3 Danish scientific publications analyzing adverse drug reactions-reported by Danish girls/young women-appearing in relation to the HPV-vaccination
        A public responsum- version 3.0
        http://hpv-bivirkningsramte.dk/sites/default/files/Responsum-EMA-UK-v-3.0.pdf

        Introduction
        (The anterior parts are omitted.)
        However, patient safety must be prioritized very high, because this is a very large group of healthy people who are exposed to potentially serious side effects-with unknown prognosis- which may trump the benefits the vaccines.
        This requires that there is a continuous focus on patient safety, and this is reported, analyzed and interpreted. The data should originate from the national HPV-centers based on national recommendations for clinical examinations and how to register complex symptoms.
        These data may then be included in scientific clinical and experimental studies, both nationally and internationally.
        My hope is that this analysis can stimulate a professional dialog among the experts in this research field. Feedback on this analysis is very welcome-hereby ensuring that factual error can be corrected and additional aspects be added.

        Copenhagen, December 10th, 2015
        Torben Palshof
        Specialist in clinical oncology and internal medicine, MDSci

        2 The Danish Health and Medicines Agency’s request for an assessment of the safety profile of the HPV-vaccines
        The report of the Danish Health and Medicines Agency includes the following statements.
        (Omit the contents)
        p 6
        As evidenced by the above, there is no criticism of the content of the Danish publications. There is especially an acceptance of authors hypotheses concerning the autoimmune aspect, as well as that a number of patients both here and abroad remain underdiagnosed. (Omit the next paragraph)
        It is also underlined that symptom pattern in the Danish reports is comparable to what has been registered in other countries.
        It therefore seems surprising that Danish Health and Medicines Agency joined EMA’s very heavy-handed and general criticism of the scientific quality of the Danish publications a few days after the release of the report.

        EMA’s criticism [1] of the three Danish HPV publications
        (Omit the contents)
        p10
        5j comments
        (Omit the anterior part)
        The Danish Health and Medicines Agency agree with Danish authors on the fact that the whole symptom pattern is so diffuse that a number of patients are likely not to be diagnosed. This will dilute the data by which the register studies are based-including the British investigation.
        It is also mentioned in the report from the Danish Health and Medicines Agency that the symptom pattern as identified in the Danish publications have also been reported from of other countries (page 6).

        6 Overall assessment of the EMA criticism and the scientific quality of the three Danish publications
        6.2 The scientific quality of the Danish publications
        It is the examiner’s overall assessment that the three studies are of scientific quality, which is clearly above the common recognized standard.
        They follow the scientific disciples that are required to implement reliable and conclusive scientific experimental projects.
        The hypotheses are relevant and the choice of method satisfies that hypothesis is tested based on optimal patient material. As noted by one of the sources consulted by the Danish Health and Medicines Agency [2] the Danish clinical information is of high quality.
        (omit the contents)
        They also call for international recommendations regarding methods, registrations and international cooperation of how to establish common, systematic, clinical and scientific approaches to the issue.

        7 Public criticism
        7.1 Impact of the criticism
        My estimate is that the criticism by EMA, paradoxically, may raise the concerns among those who shall or have been vaccinated – especially their parents.
        (omit the next paragraph)
        It is worrying that affected girls/young women – especially those who have participated
        in the scientific investigations, may understand the criticism as a rejection of their illness, as well as an expression of not being taken seriously. These frustrations will be reflected on the social platforms, which is their primary communication forum – and which is often communicated to the press.
        If, overtime, it turns out that the suspicion of severe adverse reactions to the vaccine is confirmed in one degree or another, it may perhaps be the biggest scandal in the history of medicine.

        PS: The epidemiological study was done in Nagoya City, Japan.
        http://www.npojip.org/english/MedCheck/Frailty%20exclusion%20bias-theoretical%20basis%20and%20influence%20on%20Nagoya%20City%20Study2016-6-6.pdf

        Harm assessment of HPV vaccine and “frailty exclusion bias” or“healthy vaccinee effect”: A theoretical basis and practical influences on Nagoya City Study
        Rokuro Hama M.D.
        NPO Japan Institute of Pharmacovigilance
        Med Check TIP
        Conclusion
        • It is highly suspected that the interim report of Nagoya City Survey indicates harmful effect of HPV vaccines.
        • We recommend that Nagoya City withdraw the interim report and disclose raw data
        so that the third party could analyse the data.
        • We also recommend that Nagoya City itself reanalyse the data by appropriate methods.

        • Dear Helen: I hope the trial of a systematic review from the Nordic Cochrane Centre will be useful to everybody concerned with HPV vaccination.

          https://www.researchgate.net/profile/Lars_Jorgensen15/publication/313900614_PROTOCOL_Benefits_and_harms_of_the_human_papillomavirus_vaccines_systematic_review_of_industry_and_non-industry_study_reports/links/58aef8a692851cf7ae88f16f/PROTOCOL-Benefits-and-harms-of-the-human-papillomavirus-vaccines-systematic-review-of-industry-and-non-industry-study-reports.pdf
          Benefits and harms of the human papillomavirus vaccines: systematic review of industry and nonindustr study reports
          January 2017
          Lars Jørgensen, Peter C. Gøtzsche, Tom Jefferson

          Summary
          We present the protocol for a systematic review evaluating the evidence of benefits and harms of the human papillomavirus (HPV) vaccines: Cervarix, Gardasil 4, Gardasil 9 and experimental HPV vaccines. The review will facilitate open science by providing a publicly accessible synthesis with previously confidential industry submissions to regulators (i.e., clinical study reports) and (where possible) reports from non-industry HPV vaccines trials. To minimise reporting bias, we will construct exhaustive study programmes (via registries, databases and correspondences with manufacturers, regulators, trial authors and funders) of the vaccines. We will include randomized phase II, III and IV industry clinical study reports and non-industry clinical trials of healthy participants of both sexes and of all ages. The primary outcomes are all-cause mortality; mortality from and incidence of invasive cervical cancer; incidence of histologically confirmed cervical intraepithelial neoplasia (i.e., CIN2+: CIN2, CIN3 and adenocarcinoma in situ [AIS]); mortality from and incidence of other HPV related cancers; serious adverse events; and new onset diseases. The risk of bias for included studies will be assessed on an outcome level with the Cochrane risk of bias tool. The risk of bias results will be used to generate sensitivity and subgroup analyses (e.g., low vs. high or unclear risk of bias). The review’s results will be disseminated through publication in an open-access medical journal and the research data, including clinical study reports and other relevant regulatory documents, will be placed in an open repository.

  • Did you know the conference which was held on 17-18 November 2016, in Copenhagen, Denmark about “Prevention and control of HPV and HPV related cancers in Denmark: lessons learnt and the way forward”?
    https://www.uantwerpen.be/en/projects/hpv-prevention-control-board/meetings-/country-meeting-prev/
    In this conference, the adverse events were reported, and the causal relationship was discussed. Further study is necessary to clarify the causal relationship between the adverse events and HPV vaccination. I introduce some of the important data in their presentations.

    #Monitoring Adverse events following immunization with HPV-vaccines in Denmark
    Line Michan, Danish Medicines Agency
    https://www.uantwerpen.be/images/uantwerpen/container39248/files/2016%2011%20Copenhagen/Cope%20303%20Michan.pdf
    2015 review:
    Review of the 363 serious reports for HPV-vaccines
    Large proportion of the reports (34-43%) describe a symptom complex of headache, pain, fatigue, circulatory symptoms and neurological symptoms.
    In most cases the patients are left undiagnosed. In some cases the patients fulfill criteria for POTS.
    The disease diagnose encompassing most of the symptoms could be a CFS-like condition.
    – Need for review of the world-wide data, comparative data on background incidences etc.

    #The Case of POTS
    Jesper Mehlsen Syncope Center Bispebjerg & Frederiksberg Hospitals

    Off-target effects of vaccines?
    The heterologous effects of vaccines suggest that they can affect the immune response to organisms other than their pathogen-specific intended purpose. These effects are increasingly recognized as important biological processes by a growing group of immunologists and epidemiologists.
    M. Saadatian-Elahi et al: Vaccine 2016 34:2923-30

    What have we seen?
    •782 patients referred for possible side-effects
    •Age: 23 ±8 years –range 12 -73 years
    •689 seen so far
    •Main symptoms:
    –Orthostatic intolerance
    –Headache
    –Fatigue/fatigability
    –Nausea/abdominal pain
    –Dysaestesia
    –Invoulntary muscular contractions

    Characteristics in the publicized cohort
    Diagnoses of POTS: 47%
    Height:      168 cm
    Body weight:    61 kg
    BMI:        21.9
    Symptoms after 1. Vaccination 40%
    Symptoms after 2. vaccination 35%
    Symptoms after 3. vaccination 25%
    Time to onset of symptoms: 11 days (0-58 days)
    Physical activity level: Elite 63%
                  Medium 31%
                    Low 6%

    Autoimmune Disorder?
    HPV vs Blood Donors
    Samples ANA-positive
    HPV (n=83) 59%
    Blood donors 25%
    (n=289)
    Fisher’s test P BCG.
    •Non-specific effect can be harmful -> DTP.
    •782 referred patients, average age 23 (12-73).
    •Wide range of symptoms.
    •50% of girls fit POTS definition.
    •High activity level pre-POTS.
    •Agonistic autoantibodies found (many other diseases such as Graves).
    •Provides rationale for treatment.
    •First aim: help these women, whether or not associated with HPV vaccine.

    Panel discussion
    •Q: Time-lapse between AE and vaccine? A: only 11 days between AE –vaccine. Only women with AEs within 2 months. Description of highly selected population, how to be treated, regardless of relation to HPV vaccine. Patients with unclear symptoms, not HPV vaccine Aes.
    •C: Danish population is well-educated, wants to know, to participate. In Spain, when in doubt, people want to understand. Surveillance & monitoring, efforts to prevent side effects. Tools to detect AEs, narcolepsy was detected early due to monitoring. Causality requires a lot of data, takes time. Always dealing with biases. Not same incidence in different countries, how to explain? C: What about Australia? Excellent surveillance, not showing this signal. Or Scotland? Mothers seeing it happen to their daughter look for a cause, the vaccine is convenient. Need to provide evidence that it is not. C: Spain has lots of patients, who are not reported. In Japan, other name but same symptoms. Pre-implementation versus post-implementation.
    •C -Before vaccination POTS was also present, but now higher numbers. Diagnostic criteria unclear, lot of confounders.
    •C -BR is investigated in phase IV trials, after licensure. On the risk side, auto-immune is a concern.
    •C -Girls are sick and need treatment, that is first concern. Cause-effect relation should be investigated by serum study. Auto-antibodies detected provide a handle for treatment.
    •C -Many small things worked together to crash HPV vaccine. 99.9% have no side effects. Those that do need to be heard, but a good vaccine should be used. Big RCTs, large phase IV, still signals possible.

    Recently, the scientific articles related to HPV vaccination are increasing. I refer those articles below.
    The articles (ref 3, 4, 9,13) by Japanese investigators are case series studies. As you know, the articles
    (ref 1, 11) are the experimental models of HPV vaccination-related injuries.I have heard the another Japanese investigators reported the presence of autoantibodies such as gangliosides and so on, in sera from patients with post-HPVV syndrome in the academic meeting in Japan, last year. They speculated 0.1% of those HPV- inoculated girls suffer from the neurological disorders in their local district.
    Ref.
    1. Aratani S et al: Murine hypothalamic destruction with vascular cell apoptosis subsequent to combined administration of human papilloma virus vaccine and pertussis toxin. Scientific Reports 6, Article number: 36943 (2016) doi:10.1038/srep36943
    2. Jefferson T, Jørgensen L: Human papillomavirus vaccines, complex regional pain syndrome, postural orthostatic tachycardia syndrome, and autonomic dysfunction – a review of the regulatory evidence from the European Medicines Agency. Indian Journal Medical Ethics, Published online: October 17, 2016
    3. Takahashi Y et al: Immunological studies of cerebrospinal fluid from patients with CNS symptoms after human papillomavirus vaccination. J Neuroimmunol 298: 71–78, 2016
    4. Matsudaira T et al: Cognitive dysfunction and regional cerebral blood flow changes in Japanese females after human papillomavirus vaccination. Neurology and Clinical Neuroscience 4: 220–227, 2016
    5. Perricone C, et al: Role of environmental factors in autoimmunity: pearls from the 10th international Congress on autoimmunity, Leipzig, Germany 2016. Immunol Res (2016). doi:10.1007/s12026-016-8857-z
    6. Hendrickson JE, Tormey CA. Human papilloma virus vaccination and dysautonomia: consideration for autoantibody evaluation and HLA typing. Vaccine. 2016;34:4468.
    7. Palmieri B, et al: Severe somatoform and dysautonomic syndromes after HPV vaccination: case series and review of literature. Immunol Res. 2016. doi:10.1007/s12026-016-8820-z.
    8. Geier DA, Geier MR. Quadrivalent human papillomavirus vaccine and autoimmune adverse events: a case-control assessment of the vaccine adverse event reporting system (VAERS) database. Immunol Res. 2016. doi:10.1007/s12026-016-8815-9.
    9. Hotta O, et al: Involvement of chronic epipharyngitis in autoimmune (auto-inflammatory) syndrome induced by adjuvants (ASIA). Immunol Res 2016 doi:10.1007/s12026-016-8859-x
    10. Blitshteyn S, Brook J: Postural tachycardia syndrome (POTS) with anti-NMDA receptor antibodies after human papillomavirus vaccination. Immunol Res (2016) DOI 10.1007/s12026-016-8855-1
    11. Inbar R et al: Behavioral abnormalities in female mice following administration of aluminum adjuvants and the human papillomavirus (HPV) vaccine Gardasil. Immunol Res (2016). doi:10.1007/s12026-016-8826-6
    12. Carnovale C et al: On the association between human papillomavirus vaccine and sleep disorders: evaluation based on vaccine adverse events reporting systems. J Neurol Sci (2016), doi: 10.1016/j.jns.2016.12.067
    13. Hirai T. et al: Adverse effects of human papilloma virus vaccination on central nervous system: Neuro-endocrinological disorders of hypothalamo-pituitary axis. The Autonomic Nervous System 53, 49–64 (2016).