Home Dental Radiology Summary of the evidence on the safety, efficacy, and effectiveness of human papillomavirus vaccines

Summary of the evidence on the safety, efficacy, and effectiveness of human papillomavirus vaccines

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In all but 6 of the systematic reviews,37x37Harder, T., Wichmann, O., Klug, S.J., van der Sande, M.A.B., and Wiese-Posselt, M. Efficacy, effectiveness and safety of vaccination against human papillomavirus in males: a systematic review. BMC Med. 2018;
16: 110–127
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eTable 1Search strategy for umbrella review.
PubMed
“Papillomavirus Vaccines”[Mesh] OR ((“Papillomavirus Infections”[Mesh] OR “Papillomaviridae”[Mesh] OR HPV OR hrHPV†


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eTable 1Search strategy for umbrella review.
Embase
#43#9 AND #41 AND [2006-2018]/py‖
#42#9 AND #41
#41#40 NOT #39
#40#13 OR #22 OR #28 OR #33
#39#34 OR #35 OR #38
#38#36 NOT (#36 AND #37)
#37‘human’/exp
#36‘animal’/exp
#35‘editorial’:it#
#34‘letter’:it
#33#31 AND #32
#32‘review’:it
#31#29 OR #30
#30‘selection criteria’:ab
#29‘data extraction’:ab
#28#23 OR #24 OR #25 OR #26 OR #27
#27‘relevant journals’:ab
#26‘manual search*’:ab
#25‘hand-search*’:ab
#24‘bibliograph*’:ab
#23‘reference lists’:ab
#22#14 OR #15 OR #16 OR #17 OR #18 OR #19 OR #20 OR #21
#21‘bids’:ab
#20‘science citation index’:ab
#19(‘cinahl’:ab OR ‘cinhal’:ab)
#18(‘psychinfo’:ab OR ‘psycinfo’:ab)
#17(‘psychlit’:ab OR ‘psyclit’:ab)
#16’embase’:ab
#15‘cochrane’:ab
#14‘cancerlit’:ab
#13#10 OR #11 OR #12
#12systematic NEXT/1 (review* OR overview*)
#11(meta NEXT/1 analy*) OR metaanalys*
#10‘meta analysis’/exp
#9#1 OR #8
#8#6 AND #7
#7#4 OR #5
#6#2 OR #3
#5vaccine OR vaccines OR vaccinate OR vaccinated OR vaccination OR immunize OR immunization OR immunizations OR immunized
#4‘vaccination’/exp
#3hpv OR hrhpv OR hpv1618 OR hpv6 OR hpv16 OR hpv18 OR ‘human papillomavirus’ OR ‘human papillomaviruses’ OR ‘human papilloma virus’ OR ‘human papilloma viruses’ OR gardasil OR cervarix OR 4vhpv OR 9vhpv
#2‘papillomavirus infection’/exp OR ‘papillomaviridae’/exp
#1‘wart virus vaccine’/exp
Database supplied limits: 2006 onward
Filters: SIGN††


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eTable 1Search strategy for umbrella review.
CUMULATIVE INDEX TO NURSING AND ALLIED HEALTH LITERATURE
S1(MH‡‡
S2(MH “Papillomavirus Infections+”)
S3HPV OR hrHPV OR HPV16/18 OR HPV6 OR HPV16 OR HPV18 OR “Human papillomavirus” OR “Human papillomaviruses” OR “Human papilloma virus” OR “Human papilloma viruses” OR Gardasil OR Cervarix OR 4vHPV OR 9vHPV
S4S2 OR S3
S5(MH “Immunization+”)
S6Vaccine OR Vaccines OR Vaccinate OR Vaccinated OR Vaccination OR immunize OR Immunization OR Immunizations OR immunized
S7S5 OR S6
S8S4 AND S7
S9S1 OR S8
S10(MH “Meta Analysis”)
S11TX
S12TX Metaanaly*
S13(MH “Literature Review+”)
S14TX systematic N1 (review or overview)
S15S10 OR S11 OR S12 OR S13 OR S14
S16PT
S17PT letter
S18PT editorial
S19(MH “Animals”)
S20S16 OR S17 OR S18 OR S19
S21S15 NOT S20
S22S9 AND S21
Database supplied limits: 2006 onward
Filters: SIGN Systematic reviews filter incorporated into search strategy


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eTable 1Search strategy for umbrella review.
Cochrane Database of Systematic Reviews
#1MeSH##
#2MeSH descriptor: [Papillomavirus Infections] explode all trees
#3MeSH descriptor: [Papillomaviridae] explode all trees
#4HPV OR hrHPV OR HPV16/18 OR HPV6 OR HPV16 OR HPV18 OR “Human papillomavirus” OR “Human papillomaviruses” OR “Human papilloma virus” OR “Human papilloma viruses” OR Gardasil OR Cervarix OR 4vHPV OR 9vHPV
#5#2 OR #3 OR #4
#6MeSH descriptor: [Vaccination] explode all trees
#7Vaccine OR Vaccines OR Vaccinate OR Vaccinated OR Vaccination OR immunize OR Immunization OR Immunizations OR immunized
#8#6 OR #7
#9#5 AND #8
#10#1 OR #9
Database supplied limits: 2006 onward
Filters: none


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eTable 1Search strategy for umbrella review.
Prospective Register for Systematic Reviews
((“human papillomavirus” OR “human papilloma virus” OR HPV) AND (vaccin* OR immun*))
Database supplied limits: none (limited by date within EndNote)
Filters: none


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eTable 1Search strategy for umbrella review.
Database of Abstracts of Reviews of Effects
HPV vaccine OR Papillomavirus Vaccines
Database supplied limits: Limited to items from CRD (CRD assessed review bibliographic and full abstract) (limited by date within EndNote)
Filters: none


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eTable 2Excluded systematic reviews and reason for exclusion.
PRIMARY AUTHOR, DATEARTICLE TITLEREASON FOR EXCLUSION
Ault, 2006Vaccines for the prevention of human papillomavirus and associated gynecologic diseases: a reviewNot a systematic review
Damm, 2009Human papillomavirus (HPV) vaccination for the prevention of HPV 16/18 induced cervical cancer and its precursorsAbstract of presentation only
Jeurissen, 2009Epidemiological and economic impact of human papillomavirus vaccinesWrong outcomes
Marra, 2009Effectiveness and cost effectiveness of human papillomavirus vaccine: a systematic reviewWrong outcomes
Mougin, 2009[HPV immunization for the prevention of cervical cancer]Not a systematic review
La Torre, 2010The health technology assessment of bivalent HPV vaccine Cervarix in ItalyNot a systematic review
McCormack, 2010Quadrivalent human papillomavirus (types 6,11,16,18) recombinant vaccine (Gardasil®): a review of its use in the prevention of premalignant genital lesions, genital cancer and genital warts in womenNot a systematic review
Pomfret, 2011Quadrivalent human papillomavirus (HPV) vaccine: a review of safety, efficacy, and pharmacoeconomicsNot a systematic review
Romanowski, 2011Long term protection against cervical infection with the human papillomavirus: review of currently available vaccinesNot a systematic review
Riaz, 2012The efficacy of bivalent and tetravalent HPV vaccination against cervical intraepithelial neoplasia and persistent HPV 16 and 18 infectionAbstract of presentation only
Schiller, 2012A review of clinical trials of human papillomavirus prophylactic vaccinesNot a systematic review
Araujo, 2013[Efficacy of Commercially Available Vaccines Against HPV Infection in Women: A Systematic Review and Meta-Analysis]Duplicate
Miltz, 2013Systematic review and meta-analysis of L1-VLP-based human papillomavirus vaccine efficacy against anogenital pre-cancer in women with evidence of prior HPV exposureAbstract of presentation only
Tomljenovic, 2013Human papillomavirus (HPV) vaccines as an option for preventing cervical malignancies: (how) effective and safe?Not a systematic review
Yvonne, 2013Duration of protection after vaccination against human papillomavirusNot a systematic review
Angelo, 2014Pooled analysis of large and long-term safety data from the human papillomavirus-16/18-AS04-adjuvanted vaccine clinical trial programmeNot a systematic review
Deleré, 2014The efficacy and duration of vaccine protection against human papillomavirusDuplicate
DeVincenzo, 2014Long-term efficacy and safety of human papillomavirus vaccinationNot a systematic review
Erickson, 2014Update on vaccination clinical trials for HPV-related diseaseNot a systematic review
Huang, 2014Can HPV vaccine have other health benefits more than cancer prevention? A systematic review of association between cervical HPV infection and preterm birthWrong intervention; wrong outcomes
BoTerning, 2015HPV vaccination status and changes in sexual behavior: a systematic reviewNot a systematic review
Konstantyner, 2015Safety of human papillomavirus 6, 11, 16 and 18 (recombinant): systematic review and meta-analysisDuplicate
Mariani, 2015Early direct and indirect impact of quadrivalent HPV (4HPV) vaccine on genital warts: a systematic reviewWrong study design
Stillo, 2015Safety of human papillomavirus vaccines: a reviewNot a systematic review
Vichnin, 2015An overview of quadrivalent human papillomavirus vaccine safety: 2006 to 2015Not a systematic review
Alexandra, 2016Sociodemographic differences in human papillomavirus vaccine impact: a systematic reviewWrong study design
Brisson, 2016Population-level impact, herd immunity, and elimination after human papillomavirus vaccination: a systematic review and meta-analysis of predictions from transmission-dynamic modelsWrong outcomes
Hatice, 2016The efficacy of the human papillomavirus vaccine against cervical dysplasia and safety of the vaccine: a systematic review and meta-analysisNot a systematic review
Jordão, 2016Adverse events following HPV vaccination: a systematic reviewNot a systematic review
Mofrad, 2016The role of human papilloma virus (HPV) vaccines in prevention of cervical cancerNot a systematic review
Thomas, 2016Efficacy, effectiveness and safety of vaccination against human papillomavirus in malesNot a systematic review
Ventimiglia, 2016Human papillomavirus infection and vaccination in malesWrong outcomes
Yang, 2016Update on the new 9-valent vaccine for human papillomavirus preventionNot a systematic review
Bissett, 2017Seropositivity to non-vaccine incorporated genotypes induced by the bivalent and quadrivalent HPV vaccines: a systematic review and meta-analysisWrong outcomes
Caroline, 2017Safety, efficacy and immunogenicity of therapeutic vaccines in the treatment of patients with high-grade cervical intraepithelial neoplasia (CIN 2/3) associated with human papillomavirus (HPV): a systematic reviewNot a systematic review
Costa, 2017Safety of human papillomavirus 9-valent vaccine: a meta-analysis of randomized trialsWrong comparator
D’Addario, 2017Two-dose schedules for human papillomavirus vaccine: systematic review and meta-analysisWrong comparator
Di Mario, 2017Corrigendum to “Are the two human papillomavirus vaccines really similar? A systematic review of available evidence: efficacy of the two vaccines against HPV”Erratum
DiMario, 2017Corrigendum to “Are the two human papillomavirus vaccines really similar? A systematic review of available evidence: efficacy of the two vaccines against HPV”Duplicate and erratum
Herney, 2017The effects of vaccination on papillomavirus infection prevalence and incidence: a systematic review and meta-analysisNot a systematic review
Lars, 2017Benefits and harms of human papillomavirus vaccines: systematic review of industry clinical study reports and non-industry published and unpublished reportsNot a systematic review
Martinez-Lavin, 2017Erratum to: serious adverse events after HPV vaccination: a critical review of randomized trials and post-marketing case seriesErratum
Prudence, 2017Human papillomavirus prevalence in women following HPV vaccine introduction: a systematic reviewNot a systematic review
Tine, 2017Therapeutic HPV vaccination and recurrent respiratory papillomatosis: a systematic review and meta-analysisNot a systematic review
Anita, 2018Trends in genital warts due to the quadrivalent human papillomavirus vaccination: a meta-analysisNot a systematic review
Arbyn, 2018Prophylactic vaccination against human papillomaviruses to prevent cervical cancer and its precursorsDuplicate
Hutcherson, 2018Systematic review of clinical and pharmacoeconomic outcomes of the human papillomavirus nonavalent recombinant vaccineAbstract of presentation only
Muusha, 2018Human papillomavirus prevalence among women following HPV vaccine introduction: a systematic reviewAbstract of presentation only
Phillips, 2018Safety of human papillomavirus vaccines: an updated reviewNot a systematic review
Schneider, 2018Therapeutic human papillomavirus vaccines in head and neck cancer: a systematic review of current clinical trialsWrong intervention
Stacey, 2018A systematic review of human papillomavirus (HPV) vaccine in the treatment of HPV related vulval and vaginal intraepithelial neoplasiaNot a systematic review
Steben, 2018A review of the impact and effectiveness of the quadrivalent human papillomavirus vaccine: 10 years of clinical experience in CanadaWrong study design
Yakely, 2018Impact and effectiveness of the human papillomavirus (HPV) vaccine on anogenital warts in United States and Canada: a systematic reviewDuplicate


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eTable 3Description of included systematic reviews.
STUDYREVIEW AIM OR PICOSEARCH STRATEGYTIME INCLUDED IN LITERATURE SEARCHINCLUSION CRITERIANO. OF STUDIES INCLUDEDTOTAL NO. OF PARTICIPANTSPARTICIPANT DEMOGRAPHICSHPV†COMPARATORREPORTED OUTCOMESDATA ANALYSIS TYPEPOTENTIAL SOURCES OF CONFLICT OF INTERESTAMSTAR 2
La Torre and Colleagues, 200738x38La Torre, G., de Waure, C., Chiaradia, G., Mannocci, A., and Ricciardi, W. HPV vaccine efficacy in preventing persistent cervical HPV infection: a systematic review and meta-analysis. Vaccine. 2007;
25: 8352–8358
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Review scientific literature regarding HPV vaccine efficacy in preventing cervical persistent infectionPubMed, Embase, Cochrane Library; gave search terms; no language restriction1990-August 15, 2007RCTs‡522,630Females aged 13-25 y1vHPV,Placebo; HPV 11 vaccine, hepatitis A vaccinePersistent (6 mo) cervical infection with HPV 16Meta-analysisDid not reportModerate
Rambout and Colleagues, 200749x49Rambout, L., Hopkins, L., Hutton, B., and Fergusson, D. Prophylactic vaccination against human papillomavirus infection and disease in women: a systematic review of randomized controlled trials. CMAJ. 2007;
177: 469–479
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Determine whether females who receive prophylactic HPV vaccination have a lower incidence of HPV persistent infection and precancerous lesions than females who are not vaccinatedMEDLINE, Embase, Cochrane Registry, Cochrane Library, Google Scholar, Clinical Trial Registry, Public Health Announcements, conference proceedings, manufacturer’s information; searched reference lists, bibliographies; no language restriction1950-2007RCTs; females; any HPV vaccine; any dosing; placebo or no vaccine comparator; only outcomes related to oncogenic strains640,323Females 15-25 y1vHPV, 2vHPV, 4vHPVPlacebo, unvaccinatedCervical lesions; persistent HPV infections; external genital disease; adverse eventsMeta-analysisYesHigh
Agorastos and Colleagues, 200928x28Agorastos, T., Chatzigeorgiou, K., Brotherton, J.M., and Garland, S.M. Safety of human papillomavirus (HPV) vaccines: a review of the international experience so far. Vaccine. 2009;
27: 7270–7281
Google ScholarSee all References
Report the international experience on safety of prophylactic HPV vaccines to dateMEDLINE, bibliography of selected articles, conference abstracts, position statements, gray literatureThrough January 31, 2009, for articles; through April 10, 2009 for other materialsNot stated13 published reports; 7 reports from public health agencies> 60,000Females 12 y or older, multisite, multicountry2vHPV, 4vHPVPlacebo for prelicensure data; not stated for other studiesLocal and systemic adverse eventsQualitative synthesisYesCritically low
Medeiros and Colleagues, 200946x46Medeiros, L.R., Rosa, D.D., da Rosa, M.I., Bozzetti, M.C., and Zanini, R.R. Efficacy of human papillomavirus vaccines: a systematic quantitative review. Int J Gynecol Cancer. 2009;
19: 1166–1176
Google ScholarSee all References
Systematically review RCTs in which HPV vaccine was compared with placebo regarding safety, efficacy, and immunogenicityMEDLINE, CANCERLIT, LILACS, Embase, Cochrane Library (2007 issue 2); included search terms; no language restrictions; searched reference lists1/1997-9/2007No language criteria; humans; placebo-controlled RCTs; females; excluded cohort and case-control studies and studies that did not describe final histologic results647,236Females aged 9-26 y2vHPV, 4vHPVPlacebo, hepatitis A vaccineAdverse events; condyloma; VIN††Meta-analysisNoModerate
Yancey and Colleagues, 201057x57Yancey, A.M., Pitlick, J.M., and Forinash, A.B. The prophylactic role for the human papillomavirus quadrivalent vaccine in males. Annal Pharmacother. 2010;
44: 1314–1318
Google ScholarSee all References
Evaluate immunogenicity, efficacy, and safety of the 4vHPV vaccine in malesPubMed and searched reference lists; English language only1966-March 2010HPV 4vHPV vaccine; males31,147Males aged 9-17 y, multicenter4vHPVPlaceboImmunogenicity, external genital lesions, warts, genital intraepithelial neoplasia, adverse eventsQualitative synthesisNoCritically low
Lu and Colleagues, 201139x39Lu, B., Kumar, A., Castellsagué, X., and Giuliano, A.R. Efficacy and safety of prophylactic vaccines against cervical HPV infection and diseases among women: a systematic review & meta-analysis. BMC Infect Dis. 2011;
11 ()
Google ScholarSee all References
Provide a comprehensive assessment of vaccine safety and efficacy against multiple virologic and clinical end pointsMEDLINE, Cochrane Library, Cochrane Central Register of Controlled Trials; included search terms; searched bibliographies and hand searched conference abstract books; English only2006-August 31, 2009RCTs; English language; on L1 VLP13 studies representing 7 RCTs44,142Females aged 15-45 y, multicenter1vHPV, 2vHPV, 4vHPVPlacebo, hepatitis A vaccine, hepatitis B vaccinePersistent infection (6 mo), CIN 1+, adverse eventsMeta-analysisYesLow
Malagón and Colleagues, 201243x43Malagón, T., Drolet, M., Boily, M.C. et al. Cross-protective efficacy of two human papillomavirus vaccines: a systematic review and meta-analysis. Lancet Infect Dis. 2012;
12: 781–789
Google ScholarSee all References
Summarize and compare evidence from clinical trials about the cross-protective efficacy of the 2vHPV and 4vHPV vaccines in HPV-naïve populationsMEDLINE, Embase; included search terms; searched reference lists; searched abstracts of HPV conferences; vaccine Web sites; contacted manufacturers for unpublished results; no mention of language restrictionThrough January 2012RCTs; 2vHPV or 4vHPV vaccine; any population; reported on efficacy against cervical or genital infection or disease12 (4 RCTs)22,559Females aged 15-26 y, multicenter2vHPV, 4vHPVPlacebo, hepatitis A vaccinePersistent infection (6 mo), CIN 2+Meta-analysisYesModerate
Rey-Ares and Colleagues, 201250x50Rey-Ares, L., Ciapponi, A., and Pichon-Riviere, A. Efficacy and safety of human papilloma virus vaccine in cervical cancer prevention: systematic review and meta-analysis. Arch Argent Pediatr. 2012;
110: 483–489
Google ScholarSee all References
Conduct a systematic review and meta-analysis to evaluate the efficacy and safety of HPV vaccines in preventing CIN grades 2 and 3, AIS##MEDLINE, Cochrane Central Registry of Controlled Trials, Database of Abstract Reviews of Effects, National Health Service Economic Evaluation Database, LILACS, Embase, “generic Internet search”; no language restrictionThrough July 2011Clinical trials; 2vHPV or tetravalent vaccines; included CIN 2+ lesions or cervical cancer as outcomes4 articles on 3 trials190,534Healthy females aged 15-26 y2vHPV, 4vHPVPlacebo, hepatitis A vaccineCIN 2+, AIS, cervical cancer, adverse eventsMeta-analysisDid not reportLow
Araujo and Colleagues, 201329x29Araujo, S.C., Caetano, R., Braga, J.U., and Costa e Silva, F.V. Efficacy of commercially available vaccines against HPV infection in women: a systematic review and meta-analysis [in Portuguese]. Cad Saude Publica. 2013;
29: S32–S44
Google ScholarSee all References
Determine the efficacy of 2vHPV and quadrivalent vaccine to reduce the risk of CIN 2 and CIN 3 in femalesMEDLINE, LILACS, Cochrane Library;
Professional librarian’s help with search terms; no language restriction
2000-November 2009RCTs; efficacy of commercially available 2vHPV or 4vHPV HPV vaccines; females only641,750Females aged 12-45 y2vHPV, 4vHPVPlacebo, hepatitis A vaccinePersistent infection, CIN 2+, AISMeta-analysisNoModerate
Macartney and Colleagues, 201341x41Macartney, K.K., Chiu, C., Georgousakis, M., and Brotherton, J.M.L. Safety of human papillomavirus vaccines: a review. Drug Saf. 2013;
36: 393–412
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Assess all available published safety data on both HPV vaccinesMEDLINE, Embase; no language restriction; searched reference lists bibliographies; searched InternetThrough May 2012Reported safety data from 2 available HPV vaccines12 trials; 21 case series; 4 post licensure studies; 8 post licensure population-based studies> 21,000Both sexes, aged 9-26 y2vHPV, 4vHPVUnvaccinatedAdverse eventsQualitative synthesisNoCritically low
Couto and Colleagues, 201432x32Couto, E., Sæterdal, I., Juvet, L.K., and Klemp, M. HPV catch-up vaccination of young women: a systematic review and meta-analysis. BMC Public Health. 2014;
14 ()
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Determine efficacy of vaccinating females against HPV starting at 16 y or olderOvid MEDLINE, Embase, Cochrane Central Register of Controlled Trials, PubMed, ISI Web of Science, Google Scholar; search strategy in appendix; contacted pharmaceutical companies for additional information; no mention of language restriction1999-October 2012RCTs; examined efficacy of HPV vaccination in females 16 y or older46 articles on 13 studies40,800Healthy females with 0-6 sexual partners, aged 16-45 y1vHPV, 2vHPV, 4vHPVPlacebo, hepatitis A vaccineMortality; CIN 2+; genital warts; VIN 2+; VaIN 2+; condyloma; serious adverse eventsMeta-analysisNoLow
Deleré and Colleagues, 201433x33Deleré, Y., Wichmann, O., Klug, S.J. et al. The efficacy and duration of vaccine protection against human papillomavirus. Dtsch Arztebl Int. 2014;
111: 584–591 ()
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Evaluate the duration of protection after HPV vaccination and clarify whether people vaccinated in childhood are protected against HPV years laterMEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Database of Abstract Reviews of Effects; full search strategy in eAppendix; no restriction based on publication status or languageThrough November 19, 2013Immunization with licensed vaccine according to schedule 0-1-(-2)-6 mo or similar, without booster doses after primary vaccination; must have comparison group1546,436Females aged 9-26 y, generally healthy, any country2vHPV, 4vHPVPlacebo, hepatitis A vaccineIncident or persistent HPV infection; CIN 2+Meta-analysisYesModerate
Goncalves and Colleagues, 201436x36Goncalves, A.K., Cobucci, R.N., Rodrigues, H.M., de Melo, A.G., and Giraldo, P.C. Safety, tolerability and side effects of human papillomavirus vaccines: a systematic quantitative review. Braz J Infect Dis. 2014;
18: 651–659
Google ScholarSee all References
Evaluate safety and adverse events of HPV vaccines.PubMed, Embase, Scientific Electronic Library Online, CANCERLIT; gave heading terms and text words; no language restrictionThrough March 2013Double-blind RCT; evaluate 2vHPV or 4vHPV HPV vaccines; participants aged > 9 y; excluded pregnant females and those at high risk of contracting HPV1229,540Predominantly but not exclusively females; aged 9-45 y2vHPV, 4vHPVPlacebo, hepatitis A vaccineAdverse eventsMeta-analysisNoLow
Miltz and Colleagues, 201447x47Miltz, A., Price, H., Shahmanesh, M., Copas, A., and Gilson, R. Systematic review and meta-analysis of L1-VLP-based human papillomavirus vaccine efficacy against anogenital pre-cancer in women with evidence of prior HPV exposure. PLoS One. 2014;
9
Google ScholarSee all References
Review the efficacy of the HPV vaccine in females with evidence of prior HPV exposureMEDLINE; Embase; Web of Science; PubMed; Cochrane Central Register of Controlled Trials; English onlyThrough August 30, 2013RCT and post-RCT; investigated HPV vaccine efficacy against associated CIN 3+ or VIN 2-3/VaIN 2-3; studies where females had prior exposure to vaccine-type HPV exposure58,387Females mean aged 20-43 y1vHPV, 2vHPV, 4vHPVPlacebo, hepatitis A vaccineCIN 3+, VIN 2+Meta-analysisNoModerate
Coelho and Colleagues, 201531x31Coelho, P.L., da Silva Calestini, G.L., Alvo, F.S., de Moura Freitas, J.M., Castro, P.M., and Konstantyner, T. Safety of human papillomavirus 6, 11, 16 and 18 (recombinant): wystematic review and meta-analysis [in Portuguese]. Rev Paul Pediatr. 2015;
33: 474–482
Google ScholarSee all References
Identify and quantify the adverse effects associated with the recombinant HPV (types 6, 11, 16 and 18) vaccine in adolescentsPubMed, LILACS, Scientific Electronic Library Online; searched for HPV vaccines and adverse effects; no language or date restrictionsThrough April 2014RCTs; adolescents; no patients with cervical diseases, HIV, or had already received HPV vaccine1440,458Females aged 9-45 y; males aged 9-26 y2vHPV, 4vHPVPlacebo, non-HPV vaccine, different HPV vaccine dose schedule or typeAdverse eventsMeta-analysisNoLow
Di Mario and Colleagues, 201534x34Di Mario, S., Basevi, V., Lopalco, P.L., Balduzzi, S., D’Amico, R., and Magrini, N. Are the two human papillomavirus vaccines really similar? A systematic review of available evidence: efficacy of the two vaccines against HPV. J Immunol Res. 2015;
2015: 13
Google ScholarSee all References
Assess the efficacy of the 2vHPV and 4vHPV vaccines against cervical cancerCochrane Library, MEDLINE, Embase; also searched Internet for prepublication presentations; experts and vaccine manufacturers contacted; searched reference lists; no language or time restrictionThrough March 2014RCTs; compared HPV 2vHPV or 4vHPV vaccines with placebo or any other control; must include females9 articles based on 5 trials38,419Healthy, nonpregnant females aged 15-26 y, multiple sites2vHPV, 4vHPVPlacebo, hepatitis A vaccineCIN 2+, CIN 3+, AISMeta-analysisNoHigh
Luo and Colleagues, 201540x40Luo, W., Zhang, S.H., Zhou, Y.Z. et al. Safety and immunogenicity of quadrivalent HPV vaccine: a meta-analysis. Chin J Evid Based Med. 2015;
15: 47–53
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Systematically review the safety and immunogenicity of 4vHPV vaccine among healthy populationPubMed, Embase, Chinese Biomedical Literature Database, Cochrane Library, China National Knowledge Infrastructure, Web of Science, Wang Fang Data; searched reference lists; included search terms; no language restrictionThrough October 2013RCTs939,688Both sexes, aged 9-45 y4vHPVPlaceboAdverse events, immunogenicityMeta-analysisDid not reportModerate
Sangar and Colleagues, 201551x51Sangar, V.C., Ghongane, B.B., Mathur, G., and Chowdhary, A.S. Safety and adverse events of prophylactic HPV vaccines among healthy women: a systematic review & meta analysis. Int J Pharm Sci Res. 2015;
6: 1779–1791
Google ScholarSee all References
Evaluate HPV vaccine safetyMEDLINE, Cochrane Library, Cochrane Central Register of Controlled Trials; included search terms; no mention of searching reference lists or gray literature; English onlyJune 1996-November 2014Double-blind RCTs; healthy females; 2vHPV or 4vHPV vaccines41,427Females aged 10-35 y; Asian and African sites2vHPVPlaceboAdverse eventsMeta-analysisYesCritically low
Tan and Colleagues, 201554x54Tan, P., Wang, X., Wei, S. et al. Efficacy and safety of prophylactic human papillomavirus vaccination in healthy males: a meta-analysis. Rev Med Microbiol. 2015;
26: 143–153
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Systematically assess the current evidence regarding the efficacy and safety of HPV vaccination in healthy malesPubMed, Embase, MEDLINE, Web of Science, ClinicalTrials.gov; restricted to English; searched reference lists; looked for trials and conference abstractsThrough November 2014Males; healthy study population; clinical trials, prospective cohort studies or vaccine intervention studies; ≥ 10 patients/study3 safety, 8 in total4,139 for safety, 6,079 in totalMales aged 9-55 y1vHPV, 2vHPV, 4vHPVPlacebo, hepatitis B vaccineImmunogenicity, adverse eventsMeta-analysisNoCritically low
Garland and Colleagues, 201635x35Garland, S.M., Kjaer, S.K., Muñoz, N. et al. Impact and effectiveness of the quadrivalent human papillomavirus vaccine: a systematic review of 10 years of real-world experience. Clin Infect Dis. 2016;
63: 519–527
Google ScholarSee all References
Quantify reported effectiveness and impact of 4vHPV vaccination on HPV infection, anogenital warts, and cervical cytologic and histologic abnormalitiesPubMed and Embase; full search terms in eAppendix; no language restriction; searched reference listsJanuary 1, 2007-February 29, 2016RCT or observational studies; must relate to 2vHPV or 4vHPV HPV vaccines58MillionsPrimarily but not exclusively females; 9 y or older2vHPV, 4vHPVPrevaccination period, unvaccinatedHPV June 11, 2018 infection prevalence; genital warts; cervical cytologic and histologic abnormalitiesQualitative synthesisYesCritically low
Macki and Colleagues, 201642x42Macki, M. and Dabaja, A.A. Literature review of vaccine-related adverse events reported from HPV vaccination in randomized controlled trials. Basic Clin Androl. 2016;
26: 16
Google ScholarSee all References
Determine safety of the HPV vaccine.PubMed; search term was human papillomavirus vaccine, no language restriction mentioned; no searched reference lists mentionedThrough October 2014RCTs; compared 2vHPV or 4vHPV vaccines with control (trials with hepatitis A or B comparators were excluded)1331,289All sexes but predominantly females; multicenter; aged 9-45 y2vHPV, 4vHPVPlaceboAdverse eventsQualitative synthesisNoCritically low
Martínez-Lavín and Colleagues, 201745x45Martínez-Lavín, M. and Amezcua-Guerra, L. Serious adverse events after HPV vaccination: a critical review of randomized trials and post-marketing case series. Clin Rheumatol. 2017;
36: 2169–2178
Google ScholarSee all References
Critically review HPV vaccine serious adverse events described in prelicensure RTs and post marketing case seriesPubMed; search term was HPV vaccine; no mention of language; no search of reference listsThrough January 31, 2017RCTs or post marketing studies16 RCTs, 12 post marketing case series60,729All sexes, aged 9-45 y, multicenter2vHPV, 4vHPV, 9vHPVPlacebo, hepatitis A vaccineAdverse eventsQualitative synthesisNoCritically low
Ogawa and Colleagues, 201748x48Ogawa, Y., Takei, H., Ogawa, R., and Mihara, K. Safety of human papillomavirus vaccines in healthy young women: a meta-analysis of 24 controlled studies. J Pharm Health Care Sci. 2017;
3
Google ScholarSee all References
Evaluate the safety of the HPV vaccine in healthy young femalesMEDLINE, Cochrane Central Register of Controlled Trials, Japana Centra Revuo Medicina, Pharmaceuticals and Medicines Devices Agency; no language restriction1966-February 2017Prospective controlled studies; young, healthy females; 2vHPV, 4vHPV, or 9vHPV22 articles, 24 studies23,570Healthy females aged 12-37 y2vHPV, 4vHPV, 9vHPVPlacebo, hepatitis A vaccine, hepatitis B vaccine, other HPV vaccine (2vHPV compared with 4vHPV, 4vHPV compared with 9vHPV)Adverse eventsMeta-analysisNoLow
Setiawan and Colleagues, 201752x52Setiawan, D., Luttjeboer, J., Pouwels, K.B., Wilschut, J.C., and Postma, M.J. Immunogenicity and safety of human papillomavirus (HPV) vaccination in Asian populations from six countries: a meta-analysis. Jpn J Clin Oncol. 2017;
47: 265–276
Google ScholarSee all References
Investigate the immunogenicity and safety profiles of HPV vaccines among both uninfected and infected populations in Asian countriesPubMed, Embase, Cochrane Library, ClinicalTrials.gov; gave search terms; no mention of searching reference lists or gray literature; English onlyThrough November 21, 2014RCTs; conducted in Asia; immunogenicity or safety as outcomes109,400Both sexes but predominantly female; aged 9-45 y; multiple Asian countries2vHPV, 4vHPVPlacebo, hepatitis A vaccineImmunogenicity and adverse eventsMeta-analysisNoCritically low
Signorelli and Colleagues, 201753x53Signorelli, C., Odone, A., Ciorba, V. et al. Human papillomavirus 9-valent vaccine for cancer prevention: a systematic review of the available evidence. Epidemiol Infect. 2017;
145: 1962–1982
Google ScholarSee all References
Systematically assess all available evidence from RCTs on 9vHPVMEDLINE, Embase, Cochrane Library registered clinical trials; searched reference lists; consulted with experts; search strategies in supplement; English language onlyThrough August 25, 2016Clinical trials; 9vHPV vaccine; any age group, study population, comparison, dose, or outcome10 included, 1 looked at vaccine versus placebo28,608 in total, 924 from single trial with placebo controlMales and females aged 9-26 y9vHPVPlaceboImmunogenicity; high-grade cervical, vulvar, and vaginal disease or cancer; adverse eventsQualitative synthesisNoCritically low
Tejada and Colleagues, 201755x55Tejada, R.A., Vargas, K.G., Benites-Zapata, V., Mezones-Holguín, E., Bolaños-Díaz, R., and Hernandez, A.V. Human papillomavirus vaccine efficacy in the prevention of anogenital warts: systematic review and meta-analysis. Salud Publica Mex. 2017;
59: 84–94
Google ScholarSee all References
Summarize available evidence on the efficacy of HPV vaccines in preventing nononcological lesionsMEDLINE, Embase, Cochrane Library, Scopus, LILACS, SciELO, Web of Knowledge; reviewed conference abstracts, National Institutes of Health and Europe clinical registries, searched reference lists; search strategies available online; no language restrictionThrough July 2015RCTs; nononcological lesions evaluated as outcome627,079Both sexes, adults, multicenter2vHPV, 4vHPVPlaceboAnogenital wartsMeta-analysisNoHigh
Arbyn and Colleagues, 201830x30Arbyn, M., Xu, L., Simoens, C., and Martin-Hirsch, P.P.L. Prophylactic vaccination against human papillomaviruses to prevent cervical cancer and its precursors. Cochrane Database Syst Rev. 2018;
2018
Google ScholarSee all References
Evaluate the harms and protection of HPV vaccines against cervical precancer and HPV 16/18 infection in adolescent and older femalesThe Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE
Search terms in appendixes
No language restriction
2002-July 2017Phase II and III RCTs; female participants; placebo comparator2673,428Females aged 15-45 y1vHPV, 2vHPV, 4vHPVPlacebo with no active product or non–HPV vaccineCIN 2+; AIS; adverse events; HPV infection (16 and 18 or 6, 11, 16, and 18)Meta-analysisDid not reportModerate
Harder and Colleagues, 201837x37Harder, T., Wichmann, O., Klug, S.J., van der Sande, M.A.B., and Wiese-Posselt, M. Efficacy, effectiveness and safety of vaccination against human papillomavirus in males: a systematic review. BMC Med. 2018;
16: 110–127
Google ScholarSee all References
Assess the currently available evidence on the efficacy, effectiveness, and safety of HPV vaccination in malesMEDLINE, Embase, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, conference abstracts, searched reference lists; no language or publication status restrictionThrough April 18, 2017Males; report clinically relevant outcome75,294Men aged 12-76 y, multicenter, multicountry4vHPVPlacebo, unvaccinatedIncident or persistent oral or anogenital infection; anogenital warts; anal intraepithelial neoplasia 2+, penile intraepithelial neoplasia 2+, severe adverse eventsQualitative synthesisNoModerate
Markowitz and Colleagues, 201844x44Markowitz, L.E., Drolet, M., Perez, N., Jit, M., and Brisson, M. Human papillomavirus vaccine effectiveness by number of doses: systematic review of data from national immunization programs. Vaccine. 2018;
36: 4806–4815
Google ScholarSee all References
Systematically review HPV vaccine effectiveness by number of doses.MEDLINE; Embase; provided search terms; no language restriction; no mention of searched reference listsJanuary 1, 2007-June 15, 2017Reported effectiveness of HPV vaccination on infection, warts, or cervical abnormalities; assessed effectiveness of HPV vaccination by number of doses; excluded RCTs143,104,053Aged 9-26 y, multicountry2vHPV, 4vHPVOther number of doses of HPV vaccineVaccine-type HPV infection; anogenital warts; CIN 1-3+; AISQualitative synthesisNoLow
Yakely and Colleagues, 201856x56Yakely, A.E., Avni-Singer, L., Oliveira, C.R., and Niccolai, L.M. Human papillomavirus vaccination and anogenital warts: a systematic review of impact and effectiveness in the United States. Sex Transm Dis. 2018;
46: 213–220
Google ScholarSee all References
Assess real-world impact and effectiveness of the HPV vaccine as it relates to anogenital wartsPubMed, MEDLINE, Embase; search terms in Supplement; English language restriction; no reference list searchJanuary 1, 2006-March 12, 2018Must include 4vHPV or 9vHPV vaccine; must include anogenital warts as outcome; US setting3 effectiveness, 8 in total109,123,079 for impact studies; 452,736 for effectiveness studiesBoth sexes, 9 y or older, entirely US-based4vHPVUnvaccinatedAnogenital wartsQualitative synthesisYesCritically low


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eTable 4Meta-analysis results from included systematic reviews.
STUDYSEROCONVERSIONHPVHPV PERSISTENT (> 6 MO) INFECTION EFFICACYHPV ORAL INFECTION EFFICACYHPV-RELATED WART EFFICACYHPV-RELATED PRECANCEROUS LESIONSHPV-RELATED ORAL CANCERAE†
La Torre and Colleagues, 200738x38La Torre, G., de Waure, C., Chiaradia, G., Mannocci, A., and Ricciardi, W. HPV vaccine efficacy in preventing persistent cervical HPV infection: a systematic review and meta-analysis. Vaccine. 2007;
25: 8352–8358
Google ScholarSee all References
Not evaluatedNot evaluatedHPV 16 persistent cervical infection: RR,‡Not evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluated
Rambout and Colleagues, 200749x49Rambout, L., Hopkins, L., Hutton, B., and Fergusson, D. Prophylactic vaccination against human papillomavirus infection and disease in women: a systematic review of randomized controlled trials. CMAJ. 2007;
177: 469–479
Google ScholarSee all References
Not evaluatedNot evaluatedPeto-OR,Not evaluatedPeto-OR, 0.13 (95% CI, 0.08–0.22) per protocol; Peto-OR, 0.30 (95% CI, 0.22 to 0.43) per ITTPer protocol: CIN 2+: Peto-OR, 0.14 (95% CI, 0.09 to 0.21)
Any CIN: Peto-OR, 0.13 (95% CI, 0.09 to 0.20)
Modified ITT: CIN 2+: Peto-OR, 0.52 (95% CI, 0.43 to 0.63)
Any CIN: Peto-OR, 0.36 (95% CI, 0.29 to 0.45)
Not evaluatedMore than 1 AE: Peto-OR, 1.00 (95% CI, 0.87 to 1.14)
Death: Peto-OR, 0.91 (95% CI, 0.39 to 2.14)
Medeiros and Colleagues, 200946x46Medeiros, L.R., Rosa, D.D., da Rosa, M.I., Bozzetti, M.C., and Zanini, R.R. Efficacy of human papillomavirus vaccines: a systematic quantitative review. Int J Gynecol Cancer. 2009;
19: 1166–1176
Google ScholarSee all References
Not evaluatedHPV 16/18: OR, 0.09 (95% CI, 0.05 to 0.15)HPV 16/18: OR, 0.26 (95% CI, 0.07 to 0.99)Not evaluatedOR, 0.24 (95% CI, 0.17 to 0.33)2vHPV††Not evaluated2vHPV: injection site: OR, 1.74 (95% CI, 1.27 to 2.40)
Systemic: OR, 1.18 (95% CI, 0.07 to 1.99)
Serious AE: OR, 1.05 (95% CI, 0.91 to 1.21)
Death: not estimable
Total: OR, 1.35 (95% CI, 1.05 to 1.73)
4vHPV: any AE: OR, 1.16 (95% CI, 0.94 to 1.43)
Lu and Colleagues, 201139x39Lu, B., Kumar, A., Castellsagué, X., and Giuliano, A.R. Efficacy and safety of prophylactic vaccines against cervical HPV infection and diseases among women: a systematic review & meta-analysis. BMC Infect Dis. 2011;
11 ()
Google ScholarSee all References
Not evaluatedNot evaluatedHPV 16: ITT RR, 0.15 (95% CI, 0.10 to 0.23) and per-protocol RR, 0.06 (95% CI, 0.04 to 0.09); HPV 18: ITT RR, 0.24 (95% CI, 0.14 to 0.42) and per-protocol RR, 0.05 (95% CI, 0.03 to 0.09)Not evaluatedNot evaluatedITT CIN 2+ associated with HPV 16: RR, 0.47 (95% CI, 0.36 to 0.61) or 53% efficacy; perprotocol CIN 2+ associated with HPV 16 RR, 0.04 (95% CI, 0.01 to 0.11) or 96% efficacy; ITT CIN 2+ associated with HPV 18: RR, 0.16 (95% CI, 0.08 to 0.34) or 84% efficacy; per protocol CIN 2+ associated with HPV 18: RR, 0.10 (95% CI, 0.03 to 0.38) or 90% efficacyNot evaluatedSerious AE: RR, 1.00 (95% CI, 0.91 to 1.09); injection-related serious AE: RR, 1.82 (95% CI, 0.79 to 4.20)
Rey-Ares and Colleagues, 201250x50Rey-Ares, L., Ciapponi, A., and Pichon-Riviere, A. Efficacy and safety of human papilloma virus vaccine in cervical cancer prevention: systematic review and meta-analysis. Arch Argent Pediatr. 2012;
110: 483–489
Google ScholarSee all References
Not evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluatedCIN 2+ associated with HPV 16: RR, 0.45 (95% CI, 0.38 to 0.54); CIN 2+ associated with HPV 18: RR, 0.14 (95% CI, 0.08 to 0.25)Not evaluatedNot evaluated
Araujo and Colleagues, 201329x29Araujo, S.C., Caetano, R., Braga, J.U., and Costa e Silva, F.V. Efficacy of commercially available vaccines against HPV infection in women: a systematic review and meta-analysis [in Portuguese]. Cad Saude Publica. 2013;
29: S32–S44
Google ScholarSee all References
Not evaluatedNot evaluatedRR, 0.07 (95% CI, 0.03 to 0.16) by protocol; RR, 0.52 (95% CI, 0.42 to 0.65) by ITTNot evaluatedNot evaluatedCIN 2: RR, 0.03 (95% CI, 0.01 to 0.1) by protocol; RR, 0.37 (95% CI, 0.29 to 0.48) by ITT;
CIN 3: RR, 0.04 (95% CI, 0.01 to 0.11) by protocol; RR, 0.58 (95% CI, 0.45 to 0.74) by ITT
Not evaluatedNot evaluated
Couto and Colleagues, 201432x32Couto, E., Sæterdal, I., Juvet, L.K., and Klemp, M. HPV catch-up vaccination of young women: a systematic review and meta-analysis. BMC Public Health. 2014;
14 ()
Google ScholarSee all References
Not evaluatedNot evaluatedNot evaluatedNot evaluatedAny HPV type: RR, 0.38 (95% CI, 0.31 to 0.47), GRADECIN 2+ any HPV type at 4 y: RR, 0.8 (95% CI, 0.62 to 1.02), GRADE: moderate; VIN 2+ and VaIN 2+ any HPV type at 4 y: RR, 0.49 (95% CI, 0.32 to 0.76), GRADE: moderate; VIN 2+ and VaIN 2+ HPV-related at 4-5 y: RR, 0.72 (95% CI, 0.03 to 15.02), GRADE: lowNot evaluatedSerious AE at > 7 mo: RR, 0.99 (95% CI, 0.91 to 1.08), GRADE: moderate
Deleré and Colleagues, 201433x33Deleré, Y., Wichmann, O., Klug, S.J. et al. The efficacy and duration of vaccine protection against human papillomavirus. Dtsch Arztebl Int. 2014;
111: 584–591 ()
Google ScholarSee all References
Not evaluatedIncident HPV 16/18 infections RR, 0.17 (95% CI, 0.10 to 0.30), GRADE: highHPV 16/18 RR, 0.10 (95% CI, 0.05 to 0.21), GRADE: highNot evaluatedNot evaluatedCIN 2+ (any HPV type at median follow-up 27 mo) RR, 0.16 (95% CI, 0.05 to 0.50), GRADE: moderate; CIN 3+ (any HPV type at median follow-up 27 mo) RR, 0.06 (95% CI, 0.02 to 0.17), GRADE: highNot evaluatedNot evaluated
Goncalves and Colleagues, 201436x36Goncalves, A.K., Cobucci, R.N., Rodrigues, H.M., de Melo, A.G., and Giraldo, P.C. Safety, tolerability and side effects of human papillomavirus vaccines: a systematic quantitative review. Braz J Infect Dis. 2014;
18: 651–659
Google ScholarSee all References
Not evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluatedHPV 16/18: injection site pain OR, 3.29 (95% CI, 3.00 to 3.60); redness OR, 2.41 (95% CI, 2.17 to 2.68); swelling OR, 3.14 (95% CI, 2.79 to 3.53); fever OR, 1.21 (95% CI, 1.03 to 1.42); local symptoms OR, 2.33 (95% CI, 1.61 to 3.36); fatigue OR, 1.29 (95% CI, 1.18 to 1.42); gastrointestinal symptoms OR, 1.13 (95% CI, 1.00 to 1.28); headache OR, 1.17 (95% CI, 1.06 to 1.28); myalgia OR, 1.97 (95% CI, 1.77 to 2.20); arthralgia OR, 1.40 (95% CI, 1.20 to 1.64); general symptoms OR, 1.07 (95% CI, 0.82 to 1.41); HPV 6/11/16/18: pain OR, 2.88 (95% CI, 2.42 to 3.43); swelling OR, 2.65 (95% CI, 2.04 to 3.44); general symptoms OR, 1.11 (95% CI, 1.00 to 1.23)
Miltz and Colleagues, 201447x47Miltz, A., Price, H., Shahmanesh, M., Copas, A., and Gilson, R. Systematic review and meta-analysis of L1-VLP-based human papillomavirus vaccine efficacy against anogenital pre-cancer in women with evidence of prior HPV exposure. PLoS One. 2014;
9
Google ScholarSee all References
Not evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluatedCIN 3+ associated with 16/18: OR, 0.90 (95% CI, 0.56 to 1.44); VIN 2-3/VaIN 2-3 associated with 16/18: OR, 2.25 (95% CI, 0.78 to 6.50)Not evaluatedNot evaluated
Coelho and Colleagues, 201531x31Coelho, P.L., da Silva Calestini, G.L., Alvo, F.S., de Moura Freitas, J.M., Castro, P.M., and Konstantyner, T. Safety of human papillomavirus 6, 11, 16 and 18 (recombinant): wystematic review and meta-analysis [in Portuguese]. Rev Paul Pediatr. 2015;
33: 474–482
Google ScholarSee all References
Not evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluatedLocal pain: RD,††
Di Mario and Colleagues, 201534x34Di Mario, S., Basevi, V., Lopalco, P.L., Balduzzi, S., D’Amico, R., and Magrini, N. Are the two human papillomavirus vaccines really similar? A systematic review of available evidence: efficacy of the two vaccines against HPV. J Immunol Res. 2015;
2015: 13
Google ScholarSee all References
Not evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluatedCIN 2: hazard ratio, 0.74 (95% CI, 0.61 to 0.89); CIN 3: hazard ratio, 0.68 (95% CI, 0.44 to 1.06)Not evaluatedNot evaluated
Luo and Colleagues, 201540x40Luo, W., Zhang, S.H., Zhou, Y.Z. et al. Safety and immunogenicity of quadrivalent HPV vaccine: a meta-analysis. Chin J Evid Based Med. 2015;
15: 47–53
Google ScholarSee all References
HPV 6 OR, 128.54 (95% CI, 37.22 to 443.9); HPV 11 OR, 89.6 (95% CI, 32.53 to 246.03); HPV 16 OR, 303.92 (95% CI, 46.41 to 1990.23); HPV 18 OR, 97.17 (95% CI, 33.91 to 278.40)Not evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluatedInjection site: swelling and red spots: RR, 1.22 (95% CI, 1.13 to 1.32); systemic AE: RR, 1.03 (95% CI, 0.99 to 1.07); serious AE: RR, 1.06 (95% CI, 0.75 to 1.50)
Sangar and Colleagues, 201551x51Sangar, V.C., Ghongane, B.B., Mathur, G., and Chowdhary, A.S. Safety and adverse events of prophylactic HPV vaccines among healthy women: a systematic review & meta analysis. Int J Pharm Sci Res. 2015;
6: 1779–1791
Google ScholarSee all References
Not evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluatedPain at injection site: RR, 1.17 (95% CI, 1.10 to 1.25); redness at injection site: RR, 2.30 (95% CI, 1.14 to 4.62); swelling at injection site: RR, 1.84 (95% CI, 1.47 to 2.3); arthralgia: RR, 1.39 (95% CI, 1.09 to 1.78); fatigue: RR, 1.18 (95% CI, 1.02 to 1.36); fever: RR, 1.07 (95% CI, 0.90 to 1.29); gastrointestinal: RR, 1.11 (95% CI, 0.89 to 1.4); headache: RR, 0.99 (95% CI, 0.85 to 1.14); myalgia: RR, 1.40 (95% CI, 1.16 to 1.68); rash: RR, 1.13 (95% CI, 0.73 to 1.73); urticaria: RR, 1.29 (95% CI, 0.89 to 1.88); new onset of chronic disease: RR, 0.56 (95% CI, 0.28 to 1.10); medically significant condition: RR, 0.93 (95% CI, 0.65 to 1.34); serious AE: RR, 0.66 (95% CI, 0.35 to 1.27)
Tan and Colleagues, 201554x54Tan, P., Wang, X., Wei, S. et al. Efficacy and safety of prophylactic human papillomavirus vaccination in healthy males: a meta-analysis. Rev Med Microbiol. 2015;
26: 143–153
Google ScholarSee all References
HPV 6 seroconversion rate: 99.5% (95% CI, 98.9% to 100%); HPV 11 seroconversion rate: 99.7% (95% CI, 99.4% to 100%); HPV 16 seroconversion rate: 99.6% (95% CI, 99.2% to 100%); HPV 18 seroconversion rate: 99.3% (95% CI, 98.4% to 100%)Not evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluatedInjection site AE: RR, 1.12 (95% CI, 1.06 to 1.18); systemic AE: RR, 0.99 (95% CI, 0.91 to 1.1); no serious AE in either group
Ogawa and Colleagues, 201748x48Ogawa, Y., Takei, H., Ogawa, R., and Mihara, K. Safety of human papillomavirus vaccines in healthy young women: a meta-analysis of 24 controlled studies. J Pharm Health Care Sci. 2017;
3
Google ScholarSee all References
Not evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluatedSolicited local symptoms: RR, 1.20 (95% CI, 1.13 to 1.27); solicited systemic symptoms: RR, 1.04 (95% CI, 0.99 to 1.09); unsolicited symptoms: RR, 1.28 (95% CI, 1.01 to 1.63) compared with placebo but not different than hepatitis vaccine
Setiawan and Colleagues, 201752x52Setiawan, D., Luttjeboer, J., Pouwels, K.B., Wilschut, J.C., and Postma, M.J. Immunogenicity and safety of human papillomavirus (HPV) vaccination in Asian populations from six countries: a meta-analysis. Jpn J Clin Oncol. 2017;
47: 265–276
Google ScholarSee all References
HPV 16: uninfected population: 2vHPV RR, 44.86 (95% CI, 11.90 to 169.5); 4vHPV RR, 252.65 (95% CI, 35.77 to 1,784.59); combined RR, 62.52 (95% CI, 16.29 to 239.96); infected and uninfected populations RR, 8.6 (95% CI, 6.95 to 10.94); HPV 18: uninfected population: 2vHPV RR, 43.22 (95% CI, 25.52 to 73.68); 4vHPV RR, 96.04 (95% CI, 33.87 to 272.34); combined RR, 50.14 (95% CI, 31.17 to 50.68); infected and uninfected populations RR, 8.13 (95% CI, 5.96 to 11.11)Not evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluatedLocal AE: RR, 1.89 (95% CI, 1.65 to 2.17); systemic AE: RR, 1.33 (95% CI, 1.33 to 1.50)
Tejada and Colleagues, 201755x55Tejada, R.A., Vargas, K.G., Benites-Zapata, V., Mezones-Holguín, E., Bolaños-Díaz, R., and Hernandez, A.V. Human papillomavirus vaccine efficacy in the prevention of anogenital warts: systematic review and meta-analysis. Salud Publica Mex. 2017;
59: 84–94
Google ScholarSee all References
Not evaluatedNot evaluatedNot evaluatedNot evaluatedITT: RR, 0.38 (95% CI, 0.32 to 0.45); per protocol: RR, 0.05 (95% CI, 0.01 to 0.25)Not evaluatedNot evaluatedNot evaluated
Arbyn and Colleagues, 201830x30Arbyn, M., Xu, L., Simoens, C., and Martin-Hirsch, P.P.L. Prophylactic vaccination against human papillomaviruses to prevent cervical cancer and its precursors. Cochrane Database Syst Rev. 2018;
2018
Google ScholarSee all References
Not evaluatedHPV 16/18 incident infection: RR, 0.23 (95% CI, 0.14 to 0.37), GRADE: highHPV 16/18 RR, 0.07 (95% CI, 0.05 to 0.09), GRADE: moderate; HPV 6/11/16/18 RR, 0.13 (95% CI, 0.05 to 0.37), GRADE: moderateNot evaluatedNot evaluatedCIN 2+ associated with HPV 16/18 at 3-5 y: RR, 0.1 (95% CI, 0.0 to 0.05), GRADE: high; CIN 3+ associated with HPV16/18 at 3-5 y: RR, 0.01 (95% CI, 0.0 to 0.10), GRADE: high; adenocarcinoma in situ associated with HPV 16/18 at 3-5 y: RR, 0.10 (95% CI, 0.01 to 0.76), GRADE: moderateNot evaluatedSerious AE at 6 mo to 7 y: RR, 0.98 (95% CI, 0.92 to 1.05), GRADE: high; death at 7 mo to 10 y: RR, 1.29 (95% CI, 0.85 to 1.98), GRADE: low
Harder and Colleagues, 201837x37Harder, T., Wichmann, O., Klug, S.J., van der Sande, M.A.B., and Wiese-Posselt, M. Efficacy, effectiveness and safety of vaccination against human papillomavirus in males: a systematic review. BMC Med. 2018;
16: 110–127
Google ScholarSee all References
Not evaluatedNot evaluatedAnogenital infection: Vaccine efficacy 46.9% (95% CI, 28.6 to 60.8), GRADE: moderateIncident oral infection HPV 16 and/or 18: Vaccine efficacy 91% (95% CI, −59 to 99.5%), GRADE: very low; persisting oral infection: Vaccine efficacy 88% (95% CI, 2 to 98%), GRADE: moderateGenital: Vaccine efficacy 89.4% (95% CI, 65.5 to 97.9%), GRADE: high; anal: Vaccine efficacy 100% (95% CI, 8.2 to 100%), GRADE: highAnal intraepithelial neoplasia 2: Vaccine efficacy 61.9% (95% CI, 21.4 to 82.8), GRADE: moderate; anal intraepithelial neoplasia 3: Vaccine efficacy 46.8% (95% CI, –20 to 77.9), GRADE: lowNot evaluatedNot judged to be vaccine related but AE RR, 0.73 (95% CI, 0.25 to 1.99), GRADE: moderate


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eTable 5Qualitative synthesis results from included systematic reviews.
STUDYSEROCONVERSIONHPV INCIDENT INFECTIONSHPV PERSISTENT (> 6 MO) INFECTIONSHPV ORAL INFECTIONSHPV-RELATED WARTSHPV EFFECTIVENESSHPV-RELATED PRECANCEROUS LESIONSHPV-RELATED ORAL CANCERADVERSE EVENTS
Agorastos and Colleagues, 200928x28Agorastos, T., Chatzigeorgiou, K., Brotherton, J.M., and Garland, S.M. Safety of human papillomavirus (HPV) vaccines: a review of the international experience so far. Vaccine. 2009;
27: 7270–7281
Google ScholarSee all References
Not evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluatedRisk difference between vaccinated and placebo group ranged from 9.4% (95% CI,†
Yancey and Colleagues, 201057x57Yancey, A.M., Pitlick, J.M., and Forinash, A.B. The prophylactic role for the human papillomavirus quadrivalent vaccine in males. Annal Pharmacother. 2010;
44: 1314–1318
Google ScholarSee all References
Compared 4vHPV‡Not evaluatedCompared vaccinated with placebo, risk difference of 40.9%Not evaluatedCompared vaccinated with placebo, lower rate of condyloma: 10.6% (95% CI, 65.5% to 97.9%)Not evaluatedNot evaluatedNot evaluatedRate of 53.9 AEs
Malagón and Colleagues, 201243x43Malagón, T., Drolet, M., Boily, M.C. et al. Cross-protective efficacy of two human papillomavirus vaccines: a systematic review and meta-analysis. Lancet Infect Dis. 2012;
12: 781–789
Google ScholarSee all References
Not evaluatedNot evaluatedCompared vaccinated with non–HPV-vaccinated, vaccine efficacy against persistent infection with nonvaccine HPV types 31/33/45/52/58 ranged from –52.7% (95% CI, –883.5% to 70.3%) to 79.9% (95% CI, 61.3% to 89.4%)Not evaluatedNot evaluatedNot evaluatedCompared vaccinated with non–HPV-vaccinated, vaccine efficacy against CIN#Not evaluatedNot evaluated
Macartney and Colleagues, 201341x41Macartney, K.K., Chiu, C., Georgousakis, M., and Brotherton, J.M.L. Safety of human papillomavirus vaccines: a review. Drug Saf. 2013;
36: 393–412
Google ScholarSee all References
Not evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluatedRisk differences between vaccinated and placebo group ranged from 0.5% to 34% (local); 0% to 12% (systemic); 0%, with no death judged related to the vaccine (serious). Inconsistent differences in local or systemic AEs by age; no statistically significant difference between males and females; higher rate of local AEs in 2vHPV vaccine compared with 4vHPV but no difference in systemic or serious AEs
Deleré and Colleagues, 201433x33Deleré, Y., Wichmann, O., Klug, S.J. et al. The efficacy and duration of vaccine protection against human papillomavirus. Dtsch Arztebl Int. 2014;
111: 584–591 ()
Google ScholarSee all References
Not evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluatedCompared vaccine era with prevaccine era, decrease in incidence of HPV infections or CIN 2+ lesionsNot evaluatedNot evaluatedNot evaluated
Garland and Colleagues, 201635x35Garland, S.M., Kjaer, S.K., Muñoz, N. et al. Impact and effectiveness of the quadrivalent human papillomavirus vaccine: a systematic review of 10 years of real-world experience. Clin Infect Dis. 2016;
63: 519–527
Google ScholarSee all References
Not evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluatedCompared vaccinated with at least 1 dose with unvaccinated, 76% to 89% decrease in prevalent HPV 6/11/16/18 infections
Greatest decreases in those who received more than 1 dose
14%-88% decreases in prevalent HPV 16/18 in age cohort of those vaccinated compared with those in prevaccine era
45%-92.6% reduction in incidence of genital warts among those vaccinated compared with unvaccinated, with greater reduction in those vaccinated in youngest age groups
16%-60% declines in cervical cytologic abnormalities in those vaccinated compared with those unvaccinated
Highest declines among those of younger ages when vaccinated or who received more than 1 dose
Not evaluatedNot evaluatedNot evaluated
Macki and Colleagues, 201642x42Macki, M. and Dabaja, A.A. Literature review of vaccine-related adverse events reported from HPV vaccination in randomized controlled trials. Basic Clin Androl. 2016;
26: 16
Google ScholarSee all References
Not evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluatedRisk differences between vaccinated and placebo group ranged from 1.7% to 27.8% (local); –13.7% to 29.6% (systemic); –0.6% to 0.6% (serious)
Martínez-Lavín and Colleagues, 201745x45Martínez-Lavín, M. and Amezcua-Guerra, L. Serious adverse events after HPV vaccination: a critical review of randomized trials and post-marketing case series. Clin Rheumatol. 2017;
36: 2169–2178
Google ScholarSee all References
Not evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluatedRisk difference between vaccinated and unvaccinated ranged from –0.9% to 8% (systemic); –1.2% to 5% (serious)
Risk difference between 9vHPV and 4vHPV vaccine ranged from –4.5% to 3.9% (systemic); –0.5% to 0.7% (serious)
Signorelli and Colleagues, 201753x53Signorelli, C., Odone, A., Ciorba, V. et al. Human papillomavirus 9-valent vaccine for cancer prevention: a systematic review of the available evidence. Epidemiol Infect. 2017;
145: 1962–1982
Google ScholarSee all References
Compared 9vHPVNot evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluatedCompared 9vHPV vaccinated with 4vHPV vaccinated, risk difference, 0.7 (95% CI, –15.7 to 14.8)Not evaluatedRisk difference between 9vHPV and placebo was 4.5% (local); 4% (systemic); 0.5% (serious)
Risk difference between 9vHPV and 4vHPV ranged from 3.3% to 7% (local); –4.5% to 0.9% (systemic); –0.4% to 0.7% (serious)
Harder and Colleagues, 201837x37Harder, T., Wichmann, O., Klug, S.J., van der Sande, M.A.B., and Wiese-Posselt, M. Efficacy, effectiveness and safety of vaccination against human papillomavirus in males: a systematic review. BMC Med. 2018;
16: 110–127
Google ScholarSee all References
Not evaluatedCompared vaccinated with placebo, vaccine efficacy against incident anogenital HPV 16: ranged from 28.0% (95% CI, 12.9% to 40.7%) to 45.1% (95% CI, 18.0% to 63.7%); HPV 18: ranged from 33.9% (95% CI, 13.0% to 50.1%) to 49.5% (95% CI, 11.3% to 72.1%)Compared vaccinated with placebo, vaccine efficacy against persisting anogenital infection with HPV 16 ranged from 46.9% (95% CI, 28.6% to 60.8%) to 54% (95% CI, 23.9% to 72.9%); with HPV 18 ranged from 56.0% (95% CI, 28.8% to 73.7%) to 73.6% (95% CI, 37.5% to 90.3%)Compared vaccinated with placebo, vaccine efficacy against persisting oral infection was 88% (95% CI, 2% to 98%); against incident oral infection with HPV 16/18 was 91% (95% CI, –59.0% to 99.5%)Compared vaccinated with placebo, vaccine efficacy against condylomata acuminata ranged from –26% (95% CI, –130% to 31%) to 67.2% (95% CI, 47.3% to 80.3%)Not evaluatedCompared vaccinated with placebo, vaccine efficacy against AIN††Not evaluatedRisk difference between vaccinated and unvaccinated, –0.15
Markowitz and Colleagues, 201844x44Markowitz, L.E., Drolet, M., Perez, N., Jit, M., and Brisson, M. Human papillomavirus vaccine effectiveness by number of doses: systematic review of data from national immunization programs. Vaccine. 2018;
36: 4806–4815
Google ScholarSee all References
Not evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluatedCompared vaccinated with unvaccinated: decreased aOR‡‡Not evaluatedNot evaluatedNot evaluated
Yakely and Colleagues, 201856x56Yakely, A.E., Avni-Singer, L., Oliveira, C.R., and Niccolai, L.M. Human papillomavirus vaccination and anogenital warts: a systematic review of impact and effectiveness in the United States. Sex Transm Dis. 2018;
46: 213–220
Google ScholarSee all References
Not evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluatedCompared vaccinated with unvaccinated, reduced HRNot evaluatedNot evaluatedNot evaluated


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