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'''HPV vaccines''' are a group of vaccines have been developed to protect again [[human papillomavirus]] infection, which may lead to certain types of cancers. HPV refers to a very large group of viruses, and some of these, including HPV 16 and HPV 18, cause cervical cancer, anal cancer, genital warts, and other serious illness.<ref name="webmd" /> Available vaccines protect against either two, four, or nine types of HPV.<ref name="CDC" /><ref name="bi-quad">{{Cite journal | last = Kash | first = Natalie | authorlink = | last2 = Lee | first2 = Michael A. | authorlink2 = | last3 = Kollipara | first3 = Ramya | authorlink3 = | last4 = Downing | first4 = Christopher | authorlink4 = | last5 = Guidry | first5 = Jacqueline | authorlink5 = | last6 = Tyring | first6 = Stephen K. | date = 2015-04-03 | title = Safety and Efficacy Data on Vaccines and Immunization to Human Papillomavirus| url = https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4470159/|journal=Journal of Clinical Medicine|volume=4|issue=4 | pages = 614–633|doi=10.3390/jcm4040614|issn=2077-0383|pmc=4470159|pmid=26239350|quote=|via=}}</ref> All vaccines protect against at least HPV type 16 and 18 that cause the greatest risk of cervical cancer.<ref name="bi-quad" /> ==Types== A number of different vaccines are in use, with bivalent vaccines protecting against two types of HPV, and quadrivalent vaccines protecting against four types of HPV: * '''Bivalent''': Ceravix which protects against HPV 16 and HPV 18 only, and contains aluminum hydroxide and monophosphoryl lipid<ref name="CDC">{{Cite web | url=https://www.cancer.gov/about-cancer/causes-prevention/risk/infectious-agents/hpv-vaccine-fact-sheet | title = Human Papillomavirus (HPV) Vaccines | last = National Cancer Institute | first = | authorlink = | date = 2019-10-08 | website = cancer.gov|language=en|archive-url=|archive-date=|url-status=|access-date=2020-05-10}}</ref> * '''Quadrivalent''': Gardasil which protects against HPV 6 and 11, plus HPV 16 and 18, and contains amorphous aluminum hydroxyphosphate sulfate. This is the vaccine currently used in the UK.<ref name="NHS">{{Cite web | url=https://www.nhs.uk/conditions/vaccinations/hpv-human-papillomavirus-vaccine/ | title = HPV vaccine overview | last = National Health Service | first = | authorlink = National Health Service | date = 2019-07-31 | website = nhs.uk|language=en|archive-url=|archive-date=|url-status=|access-date=2020-05-10}}</ref><ref name="gardasilEMC">{{Cite web | url=https://emc-prod-wa.azurewebsites.net/emc/product/261/smpc | title = Gardasil suspension for injection - Summary of Product Characteristics (SmPC) - (emc) | last = Electronic Medicines Compendium | first = | authorlink = | date = May 7, 2019 | website = emc-prod-wa.azurewebsites.net|archive-url=|archive-date=|url-status=|access-date=2020-05-10}}</ref> * '''Nonavalent''': Gardasil-9, which protects against 9 types of HPV: HPV 6 and 11, HPV 16 and 18, plus HPV 31, HPV 33, HPV 45, HPV 52, and HPV 58, and contains a larger amount of aluminum hydroxyphosphate sulfate and more than twice as many virus-like particles than the quadrivalent vaccine.<ref name="Blitshteyn2018" /><ref name="CDC-9" /> Gardasil-9 was approved for use in the [[United States]] in 2014.<ref name="CDC-9">{{Cite web | url=https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6411a3.htm | title = Use of 9-Valent Human Papillomavirus (HPV) Vaccine: Updated HPV Vaccination Recommendations of the Advisory Committee on Immunization Practices | last = Centers for Disease Control | first = | authorlink = Centers for Disease Control and Prevention | date = |website=[[Centers for Disease Control and Prevention]]|archive-url=|archive-date=|url-status=|access-date=2020-05-10}}</ref> == Controversy == * [https://www.webmd.com/children/vaccines/features/should-your-child-get-hpv-vaccine#1 Should Your Child Get the HPV Vaccine?]<ref>{{Cite news | url=https://www.webmd.com/children/vaccines/features/should-your-child-get-hpv-vaccine#1 | title = Should Your Child Get the HPV Vaccine? | last = Edgar | first = Julie | date = |work=WebMD|access-date=2018-11-29|archive-url=|archive-date=|url-status=|language=en-US|quote=}}</ref> * 2012, [https://journalofethics.ama-assn.org/article/hpv-vaccine-controversy/2012-01 The HPV Vaccine Controversy]<ref name="Intlekofer2012">{{Cite journal | last = Intlekofer | first = Karlie A. | last2 = Cunningham | first2 = Michael J. | last3 = Caplan | first3 = Arthur L. | date = 2012-01-01 | title = The HPV Vaccine Controversy| url = https://journalofethics.ama-assn.org/article/hpv-vaccine-controversy/2012-01|journal=AMA Journal of Ethics|volume=14|issue=1|doi=|issn=2376-6980 | pages = |quote=|via=}}</ref> * 2014, [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4708146/ Pros, cons, and ethics of HPV vaccine in teens—Why such controversy?]<ref name="PMC4708146">{{Cite journal | last = White | first = Mark Donald | authorlink = | date = 2014 | title=Pros, cons, and ethics of HPV vaccine in teens—Why such controversy?| url = https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4708146/|journal=Translational Andrology and Urology|volume=3|issue=4 | pages = 429–434|doi=10.3978/j.issn.2223-4683.2014.11.02|issn=2223-4691|pmc=4708146|pmid=26816799|quote=|via=}}</ref> *Gøtzsche et al. (2021) criticized the European Medicines Agency report on HPV vaccine safety for being overly confident and relying too heavily on data on serious adverse events reported by the manufacturers during clinical trials, and also made criticisms of the Cochrane review process. They referred to previous investigations into rates of raised particular concerns about rates of POTS, ME/CFS and Chronic Regional Pain Syndrome (CRPS) after HPV vaccination, and to rates of post-vaccination in POTS compared to POTS rates after other vaccines. However, Gøtzsche et al avoided stating that the HPV vaccines were not safe and they present any analysis of data, or draw their own conclusions about the HPV vaccines.<ref name="Gotzscheletter2021" /> ==ME/CFS== The recent use of different HPV vaccines has led to a number of studies looking at HPV vaccine safety, including whether any of the HPV vaccines may increase the risk of developing ME/CFS.<ref name="webmd">{{Cite web | url=https://www.webmd.com/sexual-conditions/hpv-genital-warts/hpv-virus-information-about-human-papillomavirus | title = Information About the Human Papillomavirus (HPV)|website=WebMD|language=en|access-date=2020-05-10}}</ref> Feiring et al. (2007) conducted a national study in [[Norway]] covering six birth cohorts, and found that ME/CFS was not associated with HPV vaccination in girls, but medical history was associated with a higher number of girls developing ME/CFS within two years of HPV vaccine, and lower uptake of HPV vaccination.<ref name="Blitshteyn2018" /> They commented that ages 10-19 and 30-39 had the highest incidence of ME/CFS. ==Notable studies and scientific publications== *2007, HPV vaccination and risk of chronic fatigue syndrome/myalgic encephalomyelitis: a nationwide register-based study from Norway<ref name="Fiering2007">{{Cite journal | last = Feiring | first = Berit | authorlink = | last2 = Laake | first2 = Ida | authorlink2 = | last3 = Bakken | first3 = Inger Johanne | authorlink3 = Inger Johanne Bakken | last4 = Greve-Isdahl | first4 = Margrethe | authorlink4 = | last5 = Wyller | first5 = Vegard Bruun | authorlink5 = Vegard Bruun Wyller | last6 = Håberg | first6 = Siri E. | authorlink6 = | last7 = Magnus | first7 = Per | last8 = Trogstad | first8 = Lill | date = 2017-07-24 | title = HPV vaccination and risk of chronic fatigue syndrome/myalgic encephalomyelitis: A nationwide register-based study from Norway| url = http://www.sciencedirect.com/science/article/pii/S0264410X17308083|journal=Vaccine|language=en|volume=35|issue=33 | pages = 4203–4212|doi=10.1016/j.vaccine.2017.06.031|issn=0264-410X|pmc=|pmid=|access-date=|quote=|via=}}</ref> - [https://www.sciencedirect.com/science/article/pii/S0264410X17308083 (Full text)] - '''quadrivalent vaccine''' *2013, Bivalent human papillomavirus vaccine and the risk of fatigue syndromes in girls in the UK<ref name="Donegan2013">{{Cite journal | last = Donegan | first = Katherine | authorlink = | last2 = Beau-Lejdstrom | first2 = Raphaelle | authorlink2 = | last3 = King | first3 = Bridget | authorlink3 = | last4 = Seabroke | first4 = Suzie | authorlink4 = | last5 = Thomson | first5 = Andrew | authorlink5 = | last6 = Bryan | first6 = Philip | authorlink6 = | date = 2013-10-09 | title = Bivalent human papillomavirus vaccine and the risk of fatigue syndromes in girls in the UK| url = http://www.sciencedirect.com/science/article/pii/S0264410X13011158|journal=Vaccine|language=en|volume=31|issue=43 | pages = 4961–4967|doi=10.1016/j.vaccine.2013.08.024|issn=0264-410X|pmc=|pmid=|access-date=|quote=|via=}}</ref> - [http://qna.files.parliament.uk/qna-attachments/773017/original/MHRA%20CPRD%20study%20HPV%20and%20CFS.pdf (Full text)] - '''bivalent vaccine''' *2014, Postural Orthostatic Tachycardia With Chronic Fatigue After HPV Vaccination as Part of the “Autoimmune/Auto-inflammatory Syndrome Induced by Adjuvants”: Case Report and Literature Review<ref name="Tomljenovic2014">{{Cite journal | last = Tomljenovic | first = Lucija | last2 = Colafrancesco | first2 = Serena | last3 = Perricone | first3 = Carlo | last4 = Shoenfeld | first4 = Yehuda | date = 2014-01-01 | title = Postural Orthostatic Tachycardia With Chronic Fatigue After HPV Vaccination as Part of the “Autoimmune/Auto-inflammatory Syndrome Induced by Adjuvants”: Case Report and Literature Review | url =https://doi.org/10.1177/2324709614527812|journal=Journal of Investigative Medicine High Impact Case Reports|language=en|volume=2|issue=1 | pages = 2324709614527812|doi=10.1177/2324709614527812|issn=2324-7096|pmc = 4528866|pmid=26425598}}</ref> - [https://journals.sagepub.com/doi/full/10.1177/2324709614527812 (Full text)] *2015, Is Chronic Fatigue Syndrome/Myalgic Encephalomyelitis a Relevant Diagnosis in Patients with Suspected Side Effects to Human Papilloma Virus Vaccine?<ref name="Brinth2015">{{Cite journal | last = Brinth | first = Louise | authorlink = | last2 = Pors | first2 = Kirsten | authorlink2 = | last3 = Hoppe | first3 = Anna AG | authorlink3 = | last4 = Badreldin | first4 = Iman | authorlink4 = | last5 = Mehlsen | first5 = Jesper | authorlink5 = Jesper Mehlsen | date = 2015-06-15 | title = Is Chronic Fatigue Syndrome/Myalgic Encephalomyelitis a Relevant Diagnosis in Patients with Suspected Side Effects to Human Papilloma Virus Vaccine?| url = https://medcraveonline.com/IJVV/IJVV-01-00003.pdf | journal=International Journal of Vaccines & Vaccination|language=en|volume=1|issue=1 | pages = 00003|doi=10.15406/ijvv.2015.01.00003|issn=2470-9980|pmc=|pmid=|access-date=|quote=|via=}}</ref> - [https://www.researchgate.net/profile/Louise_Brinth/publication/283420612_Is_Chronic_Fatigue_SyndromeMyalgic_Encephalomyelitis_a_Relevant_Diagnosis_in_Patients_with_Suspected_Side_Effects_to_Human_Papilloma_Virus_Vaccine/links/5842e9b108ae8e63e623c09c/Is-Chronic-Fatigue-Syndrome-Myalgic-Encephalomyelitis-a-Relevant-Diagnosis-in-Patients-with-Suspected-Side-Effects-to-Human-Papilloma-Virus-Vaccine.pdf (Full text)] - '''quadrivalent vaccine''' *2018, Autonomic dysfunction and HPV immunization: an overview<ref name="Blitshteyn2018">{{Cite journal | last = Blitshteyn | first = Svetlana | authorlink = | last2 = Brinth | first2 = Louise | authorlink2 = | last3 = Hendrickson | first3 = Jeanne E. | authorlink3 = | last4 = Martinez-Lavin | first4 = Manuel | authorlink4 = | date = Dec 2018 | title = Autonomic dysfunction and HPV immunization: an overview | url =https://link.springer.com/article/10.1007/s12026-018-9036-1?fbclid=IwAR2r7ow4f_F4mA2VX6EWC12rZusJ939E7wmQwDT9QxxoCvpI3WP798UaVzk|journal=Immunologic Research|volume=66|issue=6 | pages = 744–754|doi=10.1007/s12026-018-9036-1|issn=1559-0755|pmc=|pmid=30478703|access-date=|quote=|via=}}</ref> - [https://siksik.org/wp-content/uploads/vaccins/docksci.com_autonomic-dysfunction-and-hpv-immunization-an-over.pdf (Full text)] - '''all types of vaccine''' *2018, [[Dysautonomia|Autonomic dysfunction]] and HPV immunization: an overview.<ref name="Blitshetyn2018">{{Cite journal | last = Blitshetyn | first = Svetlana | last2 = Brinth | first2 = Louise | last3 = Hendrickson | first3 = Jeanne E. | last4 = Martinez-Lavin | first4 = Manuel | date = 2018-11-27 | title = Autonomic dysfunction and HPV immunization: an overview | url =https://www.ncbi.nlm.nih.gov/pubmed/30478703|journal=Immunologic Research|doi=10.1007/s12026-018-9036-1|issn=1559-0755|pmid=30478703}}</ref> ([[pubmed:30478703|ABSTRACT]])<blockquote>This article reviews the case series reported from several countries describing patients with suspected severe side effects to the HPV vaccines. The described [[symptom clusters]] are remarkably similar and include [[Chronic fatigue|disabling fatigue]], [[headache]], widespread [[pain]], [[fainting]], [[Gastrointestinal system|gastrointestinal]] dysmotility, [[limb weakness]], memory impairment episodes of [[altered awareness]], and [[abnormal movements]]. This constellation of symptoms and signs has been labeled with different diagnoses such as [[complex regional pain syndrome]] (CRPS), [[postural orthostatic tachycardia syndrome]] (POTS), [[Small fiber peripheral neuropathy|small fiber neuropathy]] (SFN), [[ME/CFS|myalgic encephalomyelitis/chronic fatigue syndrome]] (ME/CFS), or [[fibromyalgia]]. It is known that [[Autoimmune disease|autoimmunity]] and [[autoantibodies]] are present in a subset of patients with CRPS, POTS, SFN, ME/CFS, and fibromyalgia. This article proposes that vaccine-triggered, [[immune-mediated autonomic dysfunction]] could lead to the development of de novo [[post-HPV vaccination syndrome]] possibly in [[genetically susceptible]] individuals. Being cognizant that a temporal relationship between vaccination and symptom onset does not necessarily equate to causality, mounting evidence of case series calls for well-designed case-control studies to determine the prevalence and possible causation between these symptom clusters and HPV vaccines. Since [[personalized medicine]] is gaining momentum, the use of [[adversomics]] and [[pharmacogenetics]] may eventually help identify individuals who are predisposed to HPV vaccine adverse events.<ref name="Blitshetyn2018" /></blockquote> *2021, EMA's mishandling of an investigation into suspected serious neurological harms of HPV vaccines<ref name="Gotzscheletter2021">http://dx.doi.org/10.1136/bmjebm-2020-111470</ref> - [http://dx.doi.org/10.1136/bmjebm-2020-111470 (Full text)] ==See also== *[[Human papillomavirus]] *[[Vaccine]] *[[Epidemiology of myalgic encephalomyelitis and chronic fatigue syndrome|Epidemiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome]] ==Learn more== *[https://www.nhs.uk/conditions/vaccinations/hpv-human-papillomavirus-vaccine/ HPV vaccine overview] - NHS *[https://www.cancer.gov/about-cancer/causes-prevention/risk/infectious-agents/hpv-vaccine-fact-sheet Human Papillomavirus Virus] - National Cancer Institute *[http://www.cdc.gov/std/hpv/stdfact-hpv.htmhttps://www.cdc.gov/std/hpv/stdfact-hpv.htm STD Facts - Human papillomavirus (HPV)] - Centers for Disease Control *[https://www.webmd.com/sexual-conditions/hpv-genital-warts/hpv-virus-information-about-human-papillomavirus HPV/genital warts] - Webmd *[https://www.who.int/immunization/hpv/vaccines/en/ HPV vaccines and safety] - [[World Health Organization]] *Dec 2017, [https://cdn.who.int/media/docs/default-source/global-vaccine-safety/hpv-vaccine-rates-information-sheet-1217.pdf Observed Rates of Vaccine Reactions, Human Papillomavirus Vaccine (leaflet)] - World Health Organization ==References== {{reflist}} [[Category:Triggers and risk factors]] [[Category:Immunology]] [[Category:Virology]] [[Category:Vaccines]]
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