<?xml version="1.0" encoding="ISO-8859-1"?><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance">
<front>
<journal-meta>
<journal-id>0300-9041</journal-id>
<journal-title><![CDATA[Ginecología y obstetricia de México]]></journal-title>
<abbrev-journal-title><![CDATA[Ginecol. obstet. Méx.]]></abbrev-journal-title>
<issn>0300-9041</issn>
<publisher>
<publisher-name><![CDATA[Federación Mexicana de Colegios de Obstetricia y Ginecología A.C.]]></publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id>S0300-90412020000900615</article-id>
<article-id pub-id-type="doi">10.24245/gom.v88i9.4168</article-id>
<title-group>
<article-title xml:lang="es"><![CDATA[Vacunas terapéuticas del virus del papiloma humano: revisión de la evidencia actual]]></article-title>
<article-title xml:lang="en"><![CDATA[Therapeutic vaccines of the human papilloma virus: current evidence review]]></article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Fernández Gracia]]></surname>
<given-names><![CDATA[Isabel]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Cristóbal]]></surname>
<given-names><![CDATA[Ignacio]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
<xref ref-type="aff" rid="Aaf"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Neyro]]></surname>
<given-names><![CDATA[José Luis]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
</contrib-group>
<aff id="Af1">
<institution><![CDATA[,Hospital Clínico San Carlos Servicio de Obstetricia y Ginecología ]]></institution>
<addr-line><![CDATA[ Madrid]]></addr-line>
<country>España</country>
</aff>
<aff id="Af2">
<institution><![CDATA[,Universidad Francisco de Vitoria  ]]></institution>
<addr-line><![CDATA[ Madrid]]></addr-line>
<country>Spain</country>
</aff>
<aff id="Af3">
<institution><![CDATA[,Universidad del País Vasco Servicio de Ginecología y Obstetricia ]]></institution>
<addr-line><![CDATA[Baracaldo ]]></addr-line>
<country>Spain</country>
</aff>
<pub-date pub-type="pub">
<day>00</day>
<month>00</month>
<year>2020</year>
</pub-date>
<pub-date pub-type="epub">
<day>00</day>
<month>00</month>
<year>2020</year>
</pub-date>
<volume>88</volume>
<numero>9</numero>
<fpage>615</fpage>
<lpage>624</lpage>
<copyright-statement/>
<copyright-year/>
<self-uri xlink:href="http://www.scielo.org.mx/scielo.php?script=sci_arttext&amp;pid=S0300-90412020000900615&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://www.scielo.org.mx/scielo.php?script=sci_abstract&amp;pid=S0300-90412020000900615&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://www.scielo.org.mx/scielo.php?script=sci_pdf&amp;pid=S0300-90412020000900615&amp;lng=en&amp;nrm=iso"></self-uri><abstract abstract-type="short" xml:lang="es"><p><![CDATA[Resumen:  OBJETIVO: Evaluar la inmunogenicidad de los distintos tipos de vacunas terapéuticas y de su efecto en las lesiones causadas por el virus del papiloma humano (VPH) después de su aplicación. Además, analizar los estudios de seguridad y las perspectivas de las vacunas terapéuticas contra el VPH.  METODOLOGÍA: Estudio retrospectivo efectuado mediante la búsqueda bibliográfica sistemática en la base de datos PubMed, sin restricción de fecha de publicación. Criterio de inclusión: ensayos clínicos aleatorizados (metanálisis y revisiones sistemáticas). Criterios de exclusión: ensayos clínicos en fase preclínica del desarrollo y publicaciones en idiomas distintos al inglés o español.  RESULTADOS: Se seleccionaron 30 artículos publicados entre 2000 y 2020. Entre ellos, 5 ensayos clínicos aleatorizados con vacunas terapéuticas que ya han finalizado o aún están en estudio. Las 25 publicaciones restantes incluyen: metanálisis y revisiones sistemáticas de aspectos seleccionados con objetivos primarios y secundarios.  CONCLUSIONES: Las vacunas terapéuticas contra VPH se encuentran en fase experimental; hasta ahora se han conseguido resultados prometedores con algunas de ellas. Si bien existen distintos tipos de vacunas terapéuticas, los mejores resultados se han conseguido con las basadas en ADN. Las vacunas VGX-3100 y TS, en fase III, han demostrado diferencias significativas en el aclaramiento viral y la regresión de las lesiones de alto grado en pacientes vacunadas. Una vacuna terapéutica efectiva tendría una repercusión inmediata en la morbilidad y mortalidad por lesiones asociadas al virus.]]></p></abstract>
<abstract abstract-type="short" xml:lang="en"><p><![CDATA[Abstract:  OBJECTIVE: To assess the immunogenicity of different types of therapeutic vaccines and their effect on human papillomavirus (HPV) lesions after application. In addition, to analyze the safety studies and prospects of therapeutic HPV vaccines.  METHODOLOGY: Retrospective study based on a systematic literature search of the PubMed database, with no publication date restrictions. Inclusion criteria: randomized clinical trials (meta-analyses and systematic reviews). Exclusion criteria: clinical trials in the pre-clinical phase of development and publications in languages other than English or Spanish.  RESULTS: 30 articles published between 2000 and 2020 were selected. Among them, 5 randomized clinical trials with therapeutic vaccines that have already been completed or are still under study. The remaining 25 publications include: meta-analyses and systematic reviews of selected aspects with primary and secondary objectives.  CONCLUSIONS: Therapeutic HPV vaccines are in the experimental phase; so far promising results have been achieved with some of them. Although different types of therapeutic vaccines exist, the best results have been achieved with DNA-based vaccines. The VGX-3100 and TS vaccines, in phase III, have demonstrated significant differences in viral clearance and regression of high-grade lesions in vaccinated patients. An effective therapeutic vaccine would have an immediate impact on morbidity and mortality from virus-associated lesions.]]></p></abstract>
<kwd-group>
<kwd lng="es"><![CDATA[Virus del papiloma humano (VPH)]]></kwd>
<kwd lng="es"><![CDATA[vacunas VPH]]></kwd>
<kwd lng="es"><![CDATA[vacunas ADN]]></kwd>
<kwd lng="es"><![CDATA[vacunas terapéuticas contra VPH]]></kwd>
<kwd lng="es"><![CDATA[infección por virus del papiloma]]></kwd>
<kwd lng="en"><![CDATA[Human Papillomavirus (HPV)]]></kwd>
<kwd lng="en"><![CDATA[HPV vaccines]]></kwd>
<kwd lng="en"><![CDATA[Vaccines, DNA]]></kwd>
<kwd lng="en"><![CDATA[Papillomavirus infection]]></kwd>
<kwd lng="en"><![CDATA[Therapeutic HPV vaccines]]></kwd>
</kwd-group>
</article-meta>
</front><back>
<ref-list>
<ref id="B1">
<label>1</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Münger]]></surname>
<given-names><![CDATA[K]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Human papillomavirus immortalization and transformation functions]]></article-title>
<source><![CDATA[Virus Res]]></source>
<year>2002</year>
<volume>89</volume>
<numero>2</numero>
<issue>2</issue>
<page-range>213-28</page-range></nlm-citation>
</ref>
<ref id="B2">
<label>2</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Richard]]></surname>
<given-names><![CDATA[BS]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Opportunities and challenges for human papillomavirus vaccination in cancer]]></article-title>
<source><![CDATA[Nature Reviews Cancer]]></source>
<year>2018</year>
<volume>18</volume>
<page-range>240-54</page-range></nlm-citation>
</ref>
<ref id="B3">
<label>3</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Roden]]></surname>
<given-names><![CDATA[R]]></given-names>
</name>
<name>
<surname><![CDATA[Wu]]></surname>
<given-names><![CDATA[TC]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[How will HPV vaccines affect cervical cancer?]]></article-title>
<source><![CDATA[Nat Rev Cancer]]></source>
<year>2006</year>
<volume>6</volume>
<page-range>753-63</page-range></nlm-citation>
</ref>
<ref id="B4">
<label>4</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Roden]]></surname>
<given-names><![CDATA[RB]]></given-names>
</name>
<name>
<surname><![CDATA[Monie]]></surname>
<given-names><![CDATA[A]]></given-names>
</name>
<name>
<surname><![CDATA[Wu]]></surname>
<given-names><![CDATA[TC]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Opportunities to improve the prevention and treatment of cervical cancer]]></article-title>
<source><![CDATA[Curr Mol Med]]></source>
<year>2007</year>
<volume>7</volume>
<page-range>490-503</page-range></nlm-citation>
</ref>
<ref id="B5">
<label>5</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Clark]]></surname>
<given-names><![CDATA[KT]]></given-names>
</name>
<name>
<surname><![CDATA[Trimble]]></surname>
<given-names><![CDATA[CL]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Current status of therapeutic HPV vaccines]]></article-title>
<source><![CDATA[Gynecol Oncol]]></source>
<year>2020</year>
<volume>156</volume>
<numero>2</numero>
<issue>2</issue>
<page-range>503-10</page-range></nlm-citation>
</ref>
<ref id="B6">
<label>6</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Schiller]]></surname>
<given-names><![CDATA[JT]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[An update of prophylactic human papillomavirus L1 virus-like particle vaccine clinical trial results]]></article-title>
<source><![CDATA[Vaccine]]></source>
<year>2008</year>
<volume>26</volume>
<numero>^s10</numero>
<issue>^s10</issue>
<supplement>10</supplement>
<page-range>53-61</page-range></nlm-citation>
</ref>
<ref id="B7">
<label>7</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Hung]]></surname>
<given-names><![CDATA[CF]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Therapeutic human papillomavirus vaccines: current clinical trials and future directions]]></article-title>
<source><![CDATA[Expert Opin Biol Ther]]></source>
<year>2008</year>
<volume>8</volume>
<page-range>421-39</page-range></nlm-citation>
</ref>
<ref id="B8">
<label>8</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Vonsky]]></surname>
<given-names><![CDATA[MS]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Therapeutic vaccines against human papilloma viruses: Achievements and prospects]]></article-title>
<source><![CDATA[Biochemistry (Mosc)]]></source>
<year>2019</year>
<volume>84</volume>
<numero>7</numero>
<issue>7</issue>
<page-range>800-16</page-range></nlm-citation>
</ref>
<ref id="B9">
<label>9</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Fausch]]></surname>
<given-names><![CDATA[SC]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[HPV protein/peptide vaccines: from animal models to clinical trials]]></article-title>
<source><![CDATA[Front Biosci]]></source>
<year>2003</year>
<volume>8</volume>
<page-range>81-91</page-range></nlm-citation>
</ref>
<ref id="B10">
<label>10</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Gerard]]></surname>
<given-names><![CDATA[CM]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Therapeutic potential of protein and adjuvant vaccinations on tumour growth]]></article-title>
<source><![CDATA[Vaccine]]></source>
<year>2001</year>
<volume>19</volume>
<page-range>2583-9</page-range></nlm-citation>
</ref>
<ref id="B11">
<label>11</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Yang]]></surname>
<given-names><![CDATA[A]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Current state in the development of candidate therapeutic HPV vaccines]]></article-title>
<source><![CDATA[Expert Rev Vaccines]]></source>
<year>2016</year>
<volume>15</volume>
<numero>8</numero>
<issue>8</issue>
<page-range>989-1007</page-range></nlm-citation>
</ref>
<ref id="B12">
<label>12</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Hung]]></surname>
<given-names><![CDATA[CF]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Therapeutic human papillomavirus vaccines: current clinical trials and future directions]]></article-title>
<source><![CDATA[Expert Opin Biol Ther]]></source>
<year>2008</year>
<volume>8</volume>
<page-range>421-39</page-range></nlm-citation>
</ref>
<ref id="B13">
<label>13</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Gurunathan]]></surname>
<given-names><![CDATA[S]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[DNA vaccines: immunology, application, and optimization]]></article-title>
<source><![CDATA[Annu Rev Immunol]]></source>
<year>2000</year>
<volume>18</volume>
<page-range>927-74</page-range></nlm-citation>
</ref>
<ref id="B14">
<label>14</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Trimble]]></surname>
<given-names><![CDATA[C]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Comparison of the CD8+ T cell responses and antitumor effects generated by DNA vaccine administered through gene gun, biojector, and syringe]]></article-title>
<source><![CDATA[Vaccine]]></source>
<year>2003</year>
<volume>21</volume>
<page-range>4036-42</page-range></nlm-citation>
</ref>
<ref id="B15">
<label>15</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Best]]></surname>
<given-names><![CDATA[SR]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Administration of HPV DNA vaccine via electroporation elicits the strongest CD8+ T cell immune responses compared to intramuscular injection and intradermal gene gun delivery]]></article-title>
<source><![CDATA[Vaccine]]></source>
<year>2009</year>
<volume>27</volume>
<page-range>5450-9</page-range></nlm-citation>
</ref>
<ref id="B16">
<label>16</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Zeira]]></surname>
<given-names><![CDATA[E]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Femtosecond laser: a new intradermal DNA delivery method for efficient, long-term gene expression and genetic immunization]]></article-title>
<source><![CDATA[Faseb J]]></source>
<year>2007</year>
<volume>21</volume>
<page-range>3522-33</page-range></nlm-citation>
</ref>
<ref id="B17">
<label>17</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Storrie]]></surname>
<given-names><![CDATA[H]]></given-names>
</name>
<name>
<surname><![CDATA[Mooney]]></surname>
<given-names><![CDATA[DJ]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Sustained delivery of plasmid DNA from polymeric scaffolds for tissue engineering]]></article-title>
<source><![CDATA[Adv Drug Deliv Rev]]></source>
<year>2006</year>
<volume>58</volume>
<page-range>500-14</page-range></nlm-citation>
</ref>
<ref id="B18">
<label>18</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Yan]]></surname>
<given-names><![CDATA[J]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Induction of antitumor immunity in vivo following delivery of a novel HPV-16 DNA vaccine encoding an E6/E7 fusion antigen]]></article-title>
<source><![CDATA[Vaccine]]></source>
<year>2009</year>
<volume>27</volume>
<page-range>431-40</page-range></nlm-citation>
</ref>
<ref id="B19">
<label>19</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Ohlschlager]]></surname>
<given-names><![CDATA[P]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Enhancement of immunogenicity of a therapeutic cervical cancer DNA-based vaccine by co-application of sequenceoptimized genetic adjuvants]]></article-title>
<source><![CDATA[Int J Cancer]]></source>
<year>2009</year>
<volume>125</volume>
<page-range>189-98</page-range></nlm-citation>
</ref>
<ref id="B20">
<label>20</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Mousavi]]></surname>
<given-names><![CDATA[T]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Different types of adjuvants in prophylactic and therapeutic human papillomavirus vaccines in laboratory animals: a systematic review]]></article-title>
<source><![CDATA[Arch Virol.]]></source>
<year>2020</year>
<volume>165</volume>
<numero>2</numero>
<issue>2</issue>
<page-range>263-84</page-range></nlm-citation>
</ref>
<ref id="B21">
<label>21</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Larange]]></surname>
<given-names><![CDATA[A]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[TLR7 and TLR8 agonists trigger different signaling pathways for human dendritic cell maturation]]></article-title>
<source><![CDATA[J Leukoc Biol]]></source>
<year>2009</year>
<volume>85</volume>
<page-range>673-83</page-range></nlm-citation>
</ref>
<ref id="B22">
<label>22</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Petrausch]]></surname>
<given-names><![CDATA[U]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Cancer immunotherapy: the role regulatory T cells play and what can be done to overcome their inhibitory effects]]></article-title>
<source><![CDATA[Curr Mol Med]]></source>
<year>2009</year>
<volume>9</volume>
<page-range>673-82</page-range></nlm-citation>
</ref>
<ref id="B23">
<label>23</label><nlm-citation citation-type="journal">
<collab>Special Report Policy</collab>
<article-title xml:lang=""><![CDATA[A review of humans carcinogens]]></article-title>
<source><![CDATA[Lancet]]></source>
<year>2009</year>
<volume>10</volume>
<page-range>1143-4</page-range></nlm-citation>
</ref>
<ref id="B24">
<label>24</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Trimble]]></surname>
<given-names><![CDATA[CL]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Safety, efficacy, and immunogenicity of VGX-3100, a therapeutic synthetic DNA vaccine targeting human papillomavirus 16 and 18 E6 and E7 proteins for cervical intraepithelial neoplasia 2/3: a randomised, double-blind, placebo-controlled phase 2b trial]]></article-title>
<source><![CDATA[Lancet]]></source>
<year>2015</year>
<volume>386</volume>
<numero>10008</numero>
<issue>10008</issue>
<page-range>2078-88</page-range></nlm-citation>
</ref>
<ref id="B25">
<label>25</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Harper]]></surname>
<given-names><![CDATA[DM]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[The efficacy and safety of Tipapkinogen Sovacivec therapeutic HPV vaccine in cervical intraepithelial neoplasia grades 2 and 3: Randomized controlled phase II trial with 2.5 years of follow-up]]></article-title>
<source><![CDATA[Gynecologic Oncology]]></source>
<year>2019</year>
<volume>153</volume>
<numero>3</numero>
<issue>3</issue>
<page-range>521-9</page-range></nlm-citation>
</ref>
<ref id="B26">
<label>26</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Kim]]></surname>
<given-names><![CDATA[TJ]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Clearance of persistent HPV infection and cervical lesion by therapeutic DNA vaccine in CIN3 patients]]></article-title>
<source><![CDATA[Nature communications]]></source>
<year>2014</year>
<volume>5</volume>
<page-range>5317</page-range></nlm-citation>
</ref>
<ref id="B27">
<label>27</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Lin]]></surname>
<given-names><![CDATA[K]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Therapeutic HPV DNA vaccines]]></article-title>
<source><![CDATA[Immunol Res]]></source>
<year>2010</year>
<volume>47</volume>
<numero>1-3</numero>
<issue>1-3</issue>
<page-range>86-112</page-range></nlm-citation>
</ref>
<ref id="B28">
<label>28</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Hancock]]></surname>
<given-names><![CDATA[G]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Therapeutic HPV vaccines]]></article-title>
<source><![CDATA[Best Practice &amp; Research Clinical Obstetrics and Gynaecology]]></source>
<year>2018</year>
<volume>47</volume>
<page-range>59-72</page-range></nlm-citation>
</ref>
<ref id="B29">
<label>29</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Wang]]></surname>
<given-names><![CDATA[R]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Human papillomavirus vaccine against cervical cancer: Opportunity and challenge]]></article-title>
<source><![CDATA[Cancer Lett]]></source>
<year>2020</year>
<volume>471</volume>
<page-range>88-102</page-range></nlm-citation>
</ref>
</ref-list>
</back>
</article>
