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Original article
Baseline prevalence and type distribution of Human papillomavirus in sexually active non-vaccinated adolescent girls from Argentina
Prevalencia basal y distribución por tipo específica del virus del papiloma humano en mujeres adolescentes sexualmente activas y no vacunadas de Argentina
Joaquín Víctor Gonzáleza, Gerardo Daniel Delucab, Domingo Javier Liottac,d, Rita Mariel Correaa, Jorge Alejandro Basilettia, María Celeste Coluccia, Nathalia Katze, Carla Vizzottie, María Alejandra Picconia,
Corresponding author
, on behalf of the MALBRAN HPV Surveillance Study Group
a Servicio Virus Oncogénicos, Instituto Nacional de Enfermedades Infecciosas - ANLIS “Dr. Malbrán”, Av. Velez Sarsfield 563, C1282AFF, Buenos Aires, Argentina
b Facultad de Medicina, Universidad Nacional del Nordeste, Mariano Moreno 1240, W3400ACX, Corrientes, Argentina
c Laboratorio de Biología Molecular Aplicada, Facultad de Ciencias Exactas, Químicas y Naturales, Universidad Nacional de Misiones, Av. Mariano Moreno 1375, N3300, Posadas, Misiones, Argentina
d Instituto Nacional de Medicina Tropical-ANLIS “Dr. Malbrán”, Neuquén y Jujuy s/n, N3370, Puerto Iguazú, Misiones, Argentina
e Dirección de Control de Enfermedades Inmunoprevenibles, Ministerio de Salud de la Nación, Rivadavia 875, C1002AAG, Buenos Aires, Argentina
MALBRAN HPV Surveillance Study Group
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Prevalence&#44; with 95&#37; CI&#44; of all identified HPV types in non-vaccinated sexually active 15&#8211;17-year old girls from Argentina&#46;</p>"
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and low-risk &#40;LR&#41; HPV types<a class="elsevierStyleCrossRefs" href="#bib0260"><span class="elsevierStyleSup">2&#44;34&#44;45&#44;50</span></a>&#46; According to the classification of the International Agency for Research on Cancer &#40;IARC-WHO&#41;&#44; HPV types 16&#44; 18&#44; 31&#44; 33&#44; 35&#44; 39&#44; 45&#44; 51&#44; 52&#44; 56&#44; 58 and 59 are <span class="elsevierStyleItalic">carcinogenic to humans</span> &#40;Group 1&#41;&#44; being etiologically associated with more than 98&#37; of cervical cancers &#40;CCs&#41;&#44; 70&#8211;90&#37; of anal and vaginal cancers&#44; 40&#37; of vulvar cancers&#44; 47&#37; of penile cancers&#44; and 25 to 30&#37; of oropharyngeal cancers<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">11</span></a>&#46; HPV 68 is <span class="elsevierStyleItalic">probably carcinogenic</span> to humans &#40;Group 2A&#41;&#46; HPV types 26&#44; 30&#44; 34&#44; 53&#44; 66&#44; 67&#44; 69&#44; 70&#44; 73&#44; 82&#44; 85&#44; and 97 are classified as <span class="elsevierStyleItalic">possibly carcinogenic</span> to humans &#40;Group 2B&#41;&#46; HPV types 6 and 11&#44; the archetypes of LR-HPVs&#44; <span class="elsevierStyleItalic">are not classifiable as to their carcinogenicity to humans</span> &#40;Group 3&#41;&#44; being associated with more than 90&#37; of anogenital warts and laryngeal papillomas &#40;benign lesions&#41;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">25</span></a>&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">In Argentina&#44; around 4500 new CC cases are diagnosed every year&#44; and almost half of the women affected die<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">23</span></a>&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">The introduction of HPV vaccines offers a valuable tool to prevent CCs&#46; Currently&#44; three prophylactic HPV vaccines are available&#58; a bivalent HPV16&#47;18 vaccine &#40;Cervarix&#59; GlaxoSmithKline Biologicals&#44; Belgium&#41;&#44; a quadrivalent HPV6&#47;11&#47;16&#47;18 vaccine &#40;Gardasil&#47;Silgard&#59; Merck &#38; Co&#46;&#44; USA&#47;Sanofi Pasteur MSD&#44; France&#41;&#44; and a nonavalent HPV6&#47;11&#47;16&#47;18&#47;31&#47;33&#47;45&#47;52&#47;58 vaccine &#40;Gardasil9&#44; Merck &#38; Co&#46;&#41;&#46; After the first 13 years of routine use of HPV vaccines&#44; comprehensive clinical trials and real-life data have confirmed their safety and effectiveness<a class="elsevierStyleCrossRef" href="#bib0485"><span class="elsevierStyleSup">47</span></a>&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">The World Health Organization &#40;WHO&#41; recommends the inclusion of the HPV vaccine in national immunization programs primarily targeting girls aged 9&#8211;14&#44; prior to becoming sexually active&#44; and as a secondary target&#44; females aged &#8805;15&#44; or males &#40;only when feasible and cost-effective&#44; and without diverting resources from the primary population vaccination program&#41;<a class="elsevierStyleCrossRef" href="#bib0485"><span class="elsevierStyleSup">47</span></a>&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">To prevent CC&#44; in October 2011 Argentina launched the most comprehensive government-funded national HPV prevention program of Latin America&#44; incorporating a bivalent HPV vaccine&#44; with a 0&#8211;1&#8211;6-month schedule&#44; for girls 11 years of age&#44; born after January 2000<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">14</span></a>&#46; This intervention also involved reinforcing CC screening in women aged 30&#8211;64 as a secondary prevention strategy&#44; while gradually introducing HPV testing<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">3</span></a>&#46; In 2014&#44; the programme switched to the quadrivalent vaccine&#44; and was extended to males and females aged 11 to 26 living with HIV&#44; and transplanted individuals with a 3-dose schedule &#40;0&#44; 2 and 6 months&#41;&#46; In 2015 the number of doses was reduced to two and two years later&#44; vaccination was extended to boys aged 11&#44; born after 2006<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">14</span></a>&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Since the first generation of HPV vaccines &#40;bivalent and quadrivalent&#41; protects against some&#44; but not all the types capable of causing associated cancers&#44; monitoring both the positive and negative effects of these vaccines on other HPV types is critical to evaluate their impact on the population&#46; Data on type-specific HPV distribution may be useful to evaluate the additional benefits of vaccines&#44; e&#46;g&#46; cross protection against non-vaccine types and herd immunity&#44; and to monitor unlikely adverse phenomena such as type replacement&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Because the major benefit of HPV vaccination -the prevention of cervical and other less common HPV-associated cancers-will take decades to be seen&#44; a number of previous outcomes are being monitored toward an earlier assessment of the impact of HPV vaccines&#44; primarily in young adolescents<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">7&#44;49</span></a>&#46; The short-term evidence of the effectiveness of the vaccine program is crucial to encourage government planners to sustain and improve HPV vaccination services&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Since no data existed on the HPV burden in adolescent women in Argentina&#44; a study was conducted to determine the type-specific HPV prevalence in cervicovaginal samples from sexually active&#44; unvaccinated girls aged 15&#8211;17 years&#46; This data provides an important baseline to compare future changes in overall and type-specific HPV prevalence after HPV vaccination&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Materials and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Study design</span><p id="par0050" class="elsevierStylePara elsevierViewall">From April 2014 to October 2015&#44; a cross sectional study about HPV genotype circulation in unvaccinated girls was conducted by the National and Regional Reference HPV Laboratory &#40;N&#38;R-HPV Lab&#41; &#40;National Institute of Infectious Diseases&#44; ANLIS Malbr&#225;n&#44; Buenos Aires&#41;&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">When girls sought medical advice&#44; particularly about contraception&#44; the gynecologists of the Adolescence Services invited them to join the study&#46; Inclusion criteria was&#58; no HPV vaccine&#44; 15&#8211;17 years of age&#44; and sexually active&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Fifteen years of age was established as the lower limit of the reference range since that is the average age at which adolescents start sexual activity in Argentina<a class="elsevierStyleCrossRef" href="#bib0460"><span class="elsevierStyleSup">42</span></a>&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Due to difficulties related to the target population&#44; a convenience sampling method was designed and used&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">For the adolescent population sample to be broad and representative&#44; girls were recruited in six public hospitals from four cities of Argentina&#58; <span class="elsevierStyleItalic">Hospital Evita Pueblo</span> &#40;Berazategui&#44; Province of Buenos Aires&#59; east-central area of Argentina&#41;&#44; <span class="elsevierStyleItalic">Hospital Madariaga</span> &#40;Posadas&#44; Province of Misiones&#59; northeastern area of Argentina&#41;&#44; <span class="elsevierStyleItalic">Centro Integral de Salud La Banda</span> &#40;La Banda&#44; Province of Santiago del Estero&#44; north-central area of Argentina&#59; <span class="elsevierStyleItalic">Hospital Argerich&#44; Hospital Rivadavia</span> and <span class="elsevierStyleItalic">Hospital Durand</span> &#40;Buenos Aires city&#44; Capital city&#44; east-central area of Argentina&#41;&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Recruitment and sample collection</span><p id="par0075" class="elsevierStylePara elsevierViewall">The girls who agreed to participate signed an informed consent and answered a short questionnaire that included basic information on age&#44; date and place of birth&#44; current address and age of sexual debut&#46; These data are relevant to define certain basic characteristics of the group under investigation&#44; and allow for a valid comparison with data to be obtained from vaccinated girls in the near future&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">In order to standardize the collection&#44; storage and transfer of the samples obtained in the different centers&#44; a Standard Operating Procedure &#40;SOP&#41; was developed and shared in the training workshops carried out in each of the centers before launching the project&#46; Audit visits were made to evaluate the progress of these processes&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Cervical samples were obtained from both the endocervix and the ectocervix&#44; using a Cytobrush &#40;hc2 DNA Collection Device&#44; Qiagen&#41; introduced in the cervical canal and rotated 360&#176;&#44; 5 times&#46; The cellular material was placed in a vial containing specimen transport medium &#40;STM&#44; Qiagen&#41; and stored at &#43;4<span class="elsevierStyleHsp" style=""></span>&#176;C until its shipment &#40;within fifteen days&#41; to the N&#38;E-HPV Lab for processing&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">DNA extraction from cervical samples</span><p id="par0090" class="elsevierStylePara elsevierViewall">DNA was extracted from 200<span class="elsevierStyleHsp" style=""></span>&#956;l of <span class="elsevierStyleItalic">STM</span> sample using commercial columns &#40;Qiagen&#41; on a robotic system &#40;QIAcube system&#44; Qiagen&#41;&#44; following the manufacturer&#39;s instructions&#46; DNAs were stored at &#8722;20<span class="elsevierStyleHsp" style=""></span>&#176;C until use&#46; For every ten samples&#44; a tube containing only STM medium was included as a control for contamination&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">HPV detection and genotyping</span><p id="par0095" class="elsevierStylePara elsevierViewall">HPV detection and genotyping was performed by PCR using Broad-Spectrum General Primers &#40;BSGP&#41; 5&#43;&#47;6&#43; biotin-labeled designed to amplify a highly conserved 140<span class="elsevierStyleHsp" style=""></span>bp fragment of the HPV-L1 gene<a class="elsevierStyleCrossRefs" href="#bib0455"><span class="elsevierStyleSup">41&#44;44</span></a>&#46; DNA amplification was combined with a reverse line hybridization &#40;RLB&#41; which identifies 36 HPV genotypes &#40;6&#44; 11&#44; 16&#44; 18&#44; 26&#44; 31&#44; 33&#44; 34&#44; 35&#44; 39&#44; 40&#44; 42&#44; 43&#44; 44&#44; 45&#44; 51&#44; 52&#44; 53&#44; 54&#44; 55&#44; 56&#44; 57&#44; 58&#44; 59&#44; 61&#44; 66&#44; 68&#44; 70&#44; 71&#44; 72&#44; 73&#44; 81&#44; 82&#44; 83&#44; 84 and 89&#41;&#44; including all the HR-HPV established to date&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Briefly&#44; the denatured biotinylated amplicons were hybridized with genotype-specific oligonucleotide probes immobilized as parallel lines on a Biodyne C membrane &#40;Life Science&#41; using the Miniblotter MN45&#46; The hybrids were treated with alkaline phosphatase-streptavidin conjugate &#40;GE HealthCare&#41; and substrate &#40;ECL Detection Reagents&#44; GE HealthCare&#41;&#44; resulting in a chemiluminescent product subsequently detected by exposure to autoradiography film&#46; The &#946;-globin gene &#40;208<span class="elsevierStyleHsp" style=""></span>bp fragment&#41; was co-amplified and its relative abundance detected for each sample to serve as internal control<a class="elsevierStyleCrossRef" href="#bib0455"><span class="elsevierStyleSup">41</span></a>&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Every year the N&#38;R-HPV Lab participates in the external control of HPV genotyping &#40;HPV DNA typing proficiency panel&#41;&#44; provided by the International Papillomavirus Reference Center&#44; which serves as Quality Control of the results obtained in this study<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">16</span></a>&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Statistical analyses</span><p id="par0110" class="elsevierStylePara elsevierViewall">Data were entered and analyzed in an especially designed database&#44; and subsequently processed using the SPSS Statistics 23&#46;0&#46;0&#46;3 &#40;IBM&#41; statistical software&#46; The association between proportions was assessed by the chi-square test and the 95&#37; confidence interval &#40;CI&#41; was considered in all cases&#46; For all the data analyses conducted&#44; <span class="elsevierStyleItalic">p</span> values &#60;0&#46;05 were considered statistically significant&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Ethical and legal considerations</span><p id="par0115" class="elsevierStylePara elsevierViewall">The present study was approved by the ANLIS Malbr&#225;n Research Ethics Board and the Ethics Committee of each participating hospital to ensure confidentiality and anonymity&#46; A written informed consent was obtained before enrolling the study participants&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">Under the Argentine legal system&#44; adolescents over 14 years of age have the right to be assisted and receive health-related care unaccompanied by an adult or guardian&#59; they may also decide to participate in research projects and sign their consents&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Because the teenage girls invited to participate in the study were not within the age range for CC screening&#44; special care was taken to report that it was only a research study&#59; the opportunity was taken to teach basic concepts about HPV infection and health care which included the age at which screening should begin to avoid generating alarm and&#47;or an inappropriately early screening onset&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">In some provinces&#44; social workers gave talks in secondary schools informing about the study within the framework of health care counseling seminars&#46;</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Results</span><p id="par0135" class="elsevierStylePara elsevierViewall">The study enrolled 1073 unvaccinated&#44; sexually active girls who provided cervical cell samples&#59; 116 were excluded because their ages were not within the established range&#46; The remaining 957 samples were amplifiable for beta-globin&#44; thus being adequate for the PCR analysis&#59; therefore&#44; this analysis refers to them&#46; The distribution of the samples collected in the four cities was as follows&#58; 272 from Berazategui&#44; 172 from Posadas&#59; 215 from La Banda&#44; and 298 from Buenos Aires&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">The prevalence of HPV infection of any type was 56&#46;3&#37; &#40;95&#37; CI&#59; 53&#46;2&#8211;59&#46;5&#41;&#44; 42&#46;2&#37; &#40;95&#37; CI&#59; 39&#46;1&#8211;45&#46;3&#41; were infected with at least one HR-HPV genotype and 7&#46;9&#37; &#40;95&#37; CI&#59; 6&#46;2&#8211;9&#46;7&#41; with LR-HPV genotypes only&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">The frequencies of the different genotypes in descending order are presented in <a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>&#46; The 6 most common HR types were HPV16 &#91;11&#46;1&#37;&#59; &#40;95&#37; CI&#44; 9&#46;1&#8211;13&#46;1&#41;&#93;&#44; HPV52 &#91;10&#46;8&#37;&#59; &#40;95&#37; CI&#44; 8&#46;8&#8211;12&#46;7&#41;&#93;&#44; HPV56 &#91;8&#46;3&#37;&#59; &#40;95&#37; CI&#44; 6&#46;5&#8211;10&#46;0&#41;&#93;&#44; HPV51 &#91;7&#46;4&#37;&#59; &#40;95&#37; CI&#44; 5&#46;8&#8211;9&#46;1&#41;&#93;&#44; HPV58 &#91;7&#46;3&#37;&#59; &#40;95&#37; CI&#44; 5&#46;7&#8211;9&#46;0&#41;&#93; and HPV31 &#91;7&#46;1&#37;&#59; &#40;95&#37; CI&#44; 5&#46;5&#8211;8&#46;7&#41;&#93;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0150" class="elsevierStylePara elsevierViewall">Among the LR types&#44; HPV42 had the highest prevalence &#91;11&#46;5&#37; &#40;95&#37; CI&#44; 9&#46;5&#8211;13&#46;5&#41;&#93;&#44; followed by HPV6 &#91;6&#46;7&#37;&#59; &#40;95&#37; CI&#44; 5&#46;1&#8211;8&#46;3&#41;&#93;&#44; HPV40 and HPV81 &#91;5&#46;0&#37;&#59; &#40;95&#37; CI&#44; 3&#46;6&#8211;6&#46;4&#41;&#93; and HPV11 &#91;3&#46;1&#37;&#59; &#40;95&#37; CI&#44; 2&#46;0&#8211;4&#46;2&#41;&#93;&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">The prevalence of types closely related to the HPV vaccine&#44; types against which cross-protection has been reported in clinical trials&#44; and types according to IARC criteria are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0160" class="elsevierStylePara elsevierViewall">Data about HPV prevalence broken down by city of sample collection are shown in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46; Significant differences were observed for the prevalence of HPV infection of any type only between Berazategui and the rest of the cities &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;000&#41;&#59; the prevalence of HPV16&#47;18 and 6&#47;11&#47;16&#47;18 differed significantly only between Berazategui and Posadas &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;001 and <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;004&#44; respectively&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0165" class="elsevierStylePara elsevierViewall">In 36&#46;3&#37; &#40;95&#37; CI&#58; 33&#46;3&#8211;39&#46;4&#41; multiple infections were identified and up to 9 different HPV types were found in one sample &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Discussion</span><p id="par0170" class="elsevierStylePara elsevierViewall">Several studies have shown cervical HPV prevalence and type distribution in women older than 18 years of age in different study designs worldwide<a class="elsevierStyleCrossRefs" href="#bib0300"><span class="elsevierStyleSup">10&#44;13&#44;22&#44;30&#44;33&#44;36&#44;38</span></a>&#59; however&#44; there is very scarce information for young adolescents&#46; The present work reports HPV prevalence and genotype distribution among 957 sexually active non-vaccinated girls from Argentina&#44; aged 15&#8211;17 years&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">In this study&#44; the overall HPV prevalence &#40;56&#46;3&#37;&#41; was similar to previous local data from the subgroup of 15&#8211;23-year-old &#40;y&#41; women from Buenos Aires and Santa Fe &#40;Argentina&#41; &#40;46&#46;7&#37; and 64&#46;2&#37;&#44; respectively&#41;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">9</span></a>&#44; and also close to that obtained for comparable age groups in other regions like Sweden &#40;60&#37;&#44; subgroup 16 y&#41;<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">37</span></a>&#44; USA &#40;49&#37; for 11&#8211;19 y<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">15</span></a>&#59; 71&#37; for 14&#8211;17 y<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">17</span></a>&#41;&#44; Australia &#40;66&#46;3&#37;&#59; subgroup under 21 y&#41;<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">43</span></a>&#44; and Colombia &#40;60&#46;3&#37; for 18&#8211;25 y<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">35</span></a>&#59; and 49&#37; for 12&#8211;19 y<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">12</span></a>&#41;&#44; but higher than Africa where 36&#37; was reported in non-vaccinated women aged &#8804;16 years<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">46</span></a>&#46; Results confirm that this infection is very common among sexually active adolescents&#44; and rises quickly after their sexual debut<a class="elsevierStyleCrossRefs" href="#bib0355"><span class="elsevierStyleSup">21&#44;48</span></a>&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">The present study showed a prevalence of 42&#46;2&#37; for HR-HPV types &#40;Group 1 and 2A IARC&#41;&#44; which is consistent with previous surveys from Colombia &#40;48&#37; for 12&#8211;19 y&#41;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">12</span></a>&#44; Denmark &#40;40&#37; for 15&#8211;19 y&#41;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">28</span></a>&#44; Sweden &#40;over 50&#37; for 16 y&#41;<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">37</span></a> and France &#40;35&#46;71&#37;&#59; 15&#8211;18 y&#41;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">4</span></a>&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">The prevalence of HPV infection of any type was similarly high in all the cities of sample collection&#44; with the exception of Berazategui&#44; where a significant smaller value was recorded &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; Although Berazategui is located in the same geographical region as Buenos Aires city&#44; it has very different urban and demographic characteristics since it is a small town &#40;170<span class="elsevierStyleHsp" style=""></span>000 inhabitants&#41;&#46; Anyhow&#44; this observation is difficult to explain because we have no information about the participants&#8217; variables related to sexual behavior such as the number of sexual partners&#46; Furthermore&#44; we cannot rule out that these estimates may be unstable due to the limited sample size by city&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">A high prevalence of HR-HPV infections in young women does not necessarily mean a high rate of persistent infection&#44; a pre-requisite for the development of precancerous and cancerous lesions&#44; since most of these infections are transient and will be cleared in less than two years<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">24</span></a>&#59; this is the main reason for CC screening to be discouraged under 25 years of age<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">40</span></a>&#46; In cross-sectional prevalence studies such as this one&#44; it is not possible to differentiate transient infections from those that will persist&#59; however&#44; premature contact with HR-HPV at the onset of adolescence could increase the risk of cervical disease at an earlier age if a persistent infection is established&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">Estimates of type-specific HPV prevalence in cervical samples vary greatly worldwide among different populations according to age range&#44; cytological status&#44; laboratory method used&#44; and the biological interaction between different viruses and the host&#39;s immunogenetic factors<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">10</span></a>&#46; In this study&#44; it was found that 15&#46;2&#37; of the girls were infected with HPV 16&#47;18&#44; the HR types included in the bivalent and quadrivalent vaccines&#46; This rate is close to that reported in Denmark &#40;13&#46;6&#37;&#41; for women aged 15&#8211;19 y<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">28</span></a>&#44; England &#40;11&#46;5&#37;&#41; for 13&#8211;15 y<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">22</span></a> and USA &#40;14&#46;3&#37;&#41; for 11&#8211;19 y<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">15</span></a>&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">It is well known that HPV vaccines do not impact on infections that are present at the time of immunization<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">20</span></a>&#46; Under the public health plan&#44; the Argentine regular immunization program introduced HPV vaccination in 11-year-old girls to get the maximum benefit&#46; The fact that 15&#37; of the girls participating in this study were already infected by HPV16&#47;18 supports the decision of local sanitary authorities to vaccinate at an early age&#44; before their sexual debut<a class="elsevierStyleCrossRef" href="#bib0485"><span class="elsevierStyleSup">47</span></a>&#46; However&#44; the vaccines were also approved for older women who were already sexually active&#59; since it is unlikely that they were infected with all the vaccine HPV types&#44; they could benefit from vaccination and speed up the public health impact of vaccination and increase short-term benefits<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">5</span></a>&#46;</p><p id="par0205" class="elsevierStylePara elsevierViewall">The 6 most common HR types identified in this work were HPV16 &#40;11&#46;1&#37;&#41;&#44; HPV52 &#40;10&#46;8&#37;&#41;&#44; HPV56 &#40;8&#46;3&#37;&#41;&#44; HPV51 &#40;7&#46;4&#37;&#41;&#44; HPV58 &#40;7&#46;3&#37;&#41; and HPV31 &#40;7&#46;1&#37;&#41;&#44; 4 of which were included in the nonavalent vaccine formula&#59; this could represent a beneficial future scenario if the nonavalent vaccine were used&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">In the case of the bivalent and quadrivalent HPV vaccines&#44; the possibility of cross-protection against other HPV types is an extremely important aspect since it could increase the number of prevented cervical cancers&#46; To date&#44; there is evidence on the bivalent and quadrivalent vaccines cross-protection against HPV types 31&#44; 33 and 45<a class="elsevierStyleCrossRef" href="#bib0485"><span class="elsevierStyleSup">47</span></a>&#46; It was shown that the efficacy in preventing 6-month persistent infection in HPV naive women vaccinated with the current vaccines does not exceed 30&#37; for non-vaccine genotypes&#44; namely HPV 31&#44; 33&#44; 45&#44; 52&#44; 58<a class="elsevierStyleCrossRefs" href="#bib0290"><span class="elsevierStyleSup">8&#44;31</span></a>&#46; However&#44; a more recent report from Scotland revealed that immunization with the bivalent vaccine has led to a startling reduction in vaccine and cross-protective HPV types seven years after vaccination&#59; there is also evidence of herd protection against the vaccine-specific and cross-protective types &#40;HPV types 31&#44; 33 and 45&#41;<a class="elsevierStyleCrossRefs" href="#bib0280"><span class="elsevierStyleSup">6&#44;26</span></a>&#46; The data is relevant considering that Argentina started the national immunization program using the bivalent vaccine&#59; local studies on the prevalence and risk of non-vaccine HPV types are important to better assess the effectiveness of vaccination&#46;</p><p id="par0215" class="elsevierStylePara elsevierViewall">In almost 30&#37; of the samples at least one LR-HPV was identified&#44; in line with data from Denmark that show 25&#37; prevalence of these viruses among women aged 15&#8211;19 y<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">28</span></a>&#46; In this study&#44; the prevalence of HPV6&#47;11&#44; the components of the quadrivalent and nonavalent vaccines is 9&#46;5&#37;&#59; a similar amount was previously detected in Sweden &#40;10&#46;1&#37;&#41;<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">37</span></a>&#44; and a higher percentage in Denmark &#40;16&#46;1&#37;&#41;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">28</span></a>&#59; in the three cohorts&#44; the rate of HPV11 prevalence was about one half of that obtained for HPV6&#44; confirming the predominance of the latter&#46;</p><p id="par0220" class="elsevierStylePara elsevierViewall">Notably&#44; HPV42 was the most common type in this group of adolescents &#40;11&#46;5&#37;&#41;&#46; In Sweden&#44; HPV42 &#40;6&#46;4&#37;&#41; was the most frequent type among the LR-HPVs&#59; however&#44; the total type-specific prevalence ranking was led by HPV16<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">37</span></a>&#46; In several studies on cervical samples from healthy women in Denmark and the Netherlands&#44; the prevalence of HPV42 was lower than that of HPV6 and roughly equal to that of HPV11<a class="elsevierStyleCrossRefs" href="#bib0390"><span class="elsevierStyleSup">28&#44;32</span></a>&#46; However&#44; reports from Southern Europe and Africa show that the prevalence of HPV42 exceeds that of HPV6 and HPV11<a class="elsevierStyleCrossRefs" href="#bib0255"><span class="elsevierStyleSup">1&#44;27</span></a>&#46; At first&#44; the high prevalence of HPV42 raised the question of whether it would be advantageous to include HPV42 in a vaccine&#46; Nevertheless&#44; a study on HPV types in external genital warts in a group of Argentine women showed that HPV6 and&#47;or 11 were present in 93&#46;3&#37; of the cases&#44; indicating that most of the lesions could be prevented by the quadrivalent HPV vaccine<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">18</span></a>&#46;</p><p id="par0225" class="elsevierStylePara elsevierViewall">The results of the present study also show that infection with multiple HPV types is frequent in adolescents &#40;36&#46;3&#37;&#41;&#44; in accordance with previously published data from Sweden &#40;38&#37;&#41; in a cohort of 15&#8211;23-year-old non-vaccinated women<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">37</span></a> and Colombia &#40;29&#37;&#41; in 12&#8211;19-year-old girls<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">12</span></a>&#59; while in African girls&#44; the value rises more than 50&#37; for sexually active young women &#40;&#60;25 years of age&#41;<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">46</span></a>&#46; Multiple cervical HPV infections have been extensively associated with young age&#44; which may be due to a lack of natural immunity to HPV during the first years of sexual activity&#44; but also to the number and characteristics of sexual partners<a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">39</span></a>&#46;</p><p id="par0230" class="elsevierStylePara elsevierViewall">The choice of HPV genotyping method is crucial&#44; particularly due to the extensive variation in available tests&#59; they mainly differ in the viral types that they are able to identify&#44; the limit of detection &#40;LOD&#41; for each genotype&#44; and their cost&#46; The test should exhibit high analytical sensitivity to detect a broad spectrum of HPV types and to have a more accurate picture of their relative prevalence&#46; The BSGP 5&#43;&#47;6&#43; PCR-RLB method applied in this study was developed and validated for the sensitive detection of 36 HPV types in single as well as multiple infections&#59; it provides a powerful&#44; highly flexible and sensitive tool for a more homogeneous amplification and HPV genotyping&#44; at a considerably lower cost than commercial tests with a similar methodological basis<a class="elsevierStyleCrossRef" href="#bib0455"><span class="elsevierStyleSup">41</span></a>&#46; This assay allowed to identify all HR-types &#40;IARC groups 1&#44; 2A and 2B&#41;&#44; with the only exception of HPV30&#44; 67&#44; 69&#44; 85 and 97&#44; showing a remarkable ability for viral identification&#46; It is important to emphasize that our results are supported by the correct resolution of the Proficiency Panel distributed on an annual basis by the Global HPV LabNet<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">16</span></a>&#59; it guarantees that at least 5 copies of vaccine viruses are detected &#40;in single and multiple infections&#41; and that all negative controls are correct&#46; This adds strength and confidence to these data&#46;</p><p id="par0235" class="elsevierStylePara elsevierViewall">Although this study was not population-based&#44; data are particularly relevant because they provide information about HPV frequency in a group rarely assessable or included in worldwide epidemiological surveys&#44; mainly due to recruitment difficulties&#44; which adds value to our work&#46;</p><p id="par0240" class="elsevierStylePara elsevierViewall">In conclusion&#44; this is the first report about cervical HPV genotype distribution that involves sexually active 15&#8211;17-year-old non-vaccinated girls from Argentina&#44; and one of the few existing in the world focusing exclusively on this group&#46;</p><p id="par0245" class="elsevierStylePara elsevierViewall">It may be used to inform on vaccination policies&#44; as a baseline against which to measure the impact of the national HPV immunization program on the prevalence of vaccine-type and non-vaccine-type HPV infections&#46; We are conducting the same study in vaccinated girls&#59; assessments of the overall reduction in vaccine type infections&#44; changes in related alpha types&#44; and differential reductions based on the number of doses received would be the main points to evaluate and thus help to sustain and improve prevention strategies&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Funding</span><p id="par0250" class="elsevierStylePara elsevierViewall">This study was financially supported by <span class="elsevierStyleGrantSponsor" id="gs1">Salud Investiga</span> &#40;Carrillo-O&#241;ativia fellowships&#41;&#44; <span class="elsevierStyleGrantSponsor" id="gs2">Direcci&#243;n Nacional de Control de Enfermedades Inmunoprevenibles</span> &#40;Grant 2014&#8211;2015&#41; and <span class="elsevierStyleGrantSponsor" id="gs3">Instituto Nacional de Enfermedades Infecciosas - ANLIS Malbr&#225;n</span>&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Conflict of interest</span><p id="par0255" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest</p></span></span>"
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          "titulo" => "Introduction"
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          "titulo" => "Materials and methods"
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              "titulo" => "Recruitment and sample collection"
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              "titulo" => "DNA extraction from cervical samples"
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              "identificador" => "sec0030"
              "titulo" => "HPV detection and genotyping"
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              "titulo" => "Statistical analyses"
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          "titulo" => "Results"
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          "titulo" => "Conflict of interest"
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          "titulo" => "References"
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    "fechaRecibido" => "2019-11-15"
    "fechaAceptado" => "2020-06-17"
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            0 => "Human papillomavirus"
            1 => "Monitoring"
            2 => "Vaccines"
            3 => "HPV infection"
            4 => "Adolescent women"
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            0 => "Virus del papiloma humano"
            1 => "Monitorizaci&#243;n"
            2 => "Vacunas"
            3 => "Vigilancia"
            4 => "Adolescentes"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">In 2011&#44; Argentina launched a government-funded national <span class="elsevierStyleItalic">Human papillomavirus</span> &#40;HPV&#41; immunization program incorporating a bivalent HPV vaccine&#44; with a 0&#8211;1&#8211;6-month schedule&#44; for girls 11 years of age&#44; born after January 2000&#46; Monitoring the changes of HPV infection prevalence among young women has been proposed as an endpoint for early assessment of HPV vaccination programs&#46; However&#44; the data on HPV prevalence at young ages are very limited&#46; The aim of this work was to determine the prevalence of HPV infection and type-specific distribution in sexually active 15&#8211;17-year-old non-vaccinated girls&#46; Cervical samples from 1073 adolescents were collected for HPV detection and genotyping using the BSGP5&#43;&#47;GP6&#43;PCR-reverse line blot &#40;RLB&#41; assay&#46; Out of 957 specimens analyzed&#44; 56&#46;3&#37; were positive for any HPV type&#59; 42&#46;2&#37; harbored at least one high-risk HPV &#40;HR-HPV&#41; type and 30&#46;8&#37; low-risk HPV &#40;LR-HPV&#41; types&#46; Multiple and single infections were identified in 36&#46;3&#37; and 20&#46;0&#37; of the samples respectively&#46; The 6 most common HR-HPV types were HPV16 &#40;11&#46;1&#37;&#41;&#44; HPV52 &#40;10&#46;8&#37;&#41;&#44; HPV56 &#40;8&#46;3&#37;&#41;&#44; HPV51 &#40;7&#46;4&#37;&#41;&#44; HPV58 &#40;7&#46;3&#37;&#41; and HPV31 &#40;7&#46;1&#37;&#41;&#46; The prevalence of HR-HPV-16&#47;18 was 15&#46;2&#37;&#46; In conclusion&#44; results confirm that HPV &#40;particularly HR-types&#41; are very common among sexually active adolescents&#44; and prevalence rises quickly after their sexual debut&#46; Our HPV type-specific prevalence baseline may be used to monitor post-vaccinal longitudinal changes in Argentina&#46;</p></span>"
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        "titulo" => "Resumen"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">En 2011 se introdujo en el Calendario Nacional de Vacunaci&#243;n de Argentina una vacuna bivalente contra el virus del papiloma humano &#40;HPV&#44; por sus siglas en ingl&#233;s&#41; tipo 16 y 18&#44; para ser aplicada en ni&#241;as de 11 a&#241;os&#46; Se propuso la monitorizaci&#243;n de los cambios en la prevalencia de infecci&#243;n por este virus HPV en las adolescentes como un criterio de valoraci&#243;n temprano para evaluar programas de vacunaci&#243;n&#59; sin embargo&#44; los datos sobre prevalencia del HPV en la poblaci&#243;n joven son limitados&#46; El objetivo de este estudio fue determinar la prevalencia de la infecci&#243;n por el HPV y su distribuci&#243;n tipo-espec&#237;fica en mujeres de 15 a 17 a&#241;os&#44; sexualmente activas y no vacunadas&#46; Se colectaron 1&#46;073 muestras cervicales para la detecci&#243;n y tipificaci&#243;n del HPV mediante la t&#233;cnica de PCR BSGP5<span class="elsevierStyleSup">&#43;</span>&#47;GP6<span class="elsevierStyleSup">&#43;</span>-hibridaci&#243;n reversa en l&#237;nea &#40;RLB&#41;&#46; Sobre 957 muestras analizadas&#44; la frecuencia global de infecci&#243;n fue del 56&#44;3&#37;&#46; El 42&#44;2&#37; de los casos positivos present&#243; alg&#250;n genotipo de alto riesgo oncog&#233;nico &#40;HPV-AR&#41; y un 30&#44;8&#37; al menos un genotipo de bajo riesgo oncog&#233;nico &#40;HPV-BR&#41;&#46; El 20&#44;0 y el 36&#44;3&#37; fueron infecciones simples y m&#250;ltiples&#44; respectivamente&#46; Los HPV-AR m&#225;s prevalentes fueron HPV16 &#40;11&#44;1&#37;&#41;&#44; HPV52 &#40;10&#44;8&#37;&#41;&#44; HPV56 &#40;8&#44;3&#37;&#41;&#44; HPV51 &#40;7&#44;4&#37;&#41;&#44; HPV58 &#40;7&#44;3&#37;&#41; y HPV31 &#40;7&#44;1&#37;&#41;&#46; La prevalencia conjunta de HPV16&#47;18 fue del 15&#44;2&#37;&#46; En conclusi&#243;n&#44; los HPV &#40;en especial los HPV-AR&#41; son muy frecuentes en adolescentes j&#243;venes sexualmente activas&#44; con un r&#225;pido aumento de la prevalencia tras el comienzo sexual&#46; La prevalencia tipo-espec&#237;fica basal registrada podr&#225; servir para monitorizar cambios en la prevalencia de los tipos vacunales y no vacunales en el tiempo&#46;</p></span>"
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            "apendice" => "<p id="par0275" class="elsevierStylePara elsevierViewall">Alejandra Giurgiovich &#40;Hospital Evita Pueblo&#44; Berazategui&#41;&#59; Gabriela Alzogaray&#44; Ricardo Aboslaiman &#40;Centro Integral de Salud La Banda&#44; Santiago del Estero&#41;&#59; Cecilia Chami &#40;Ministerio de Salud de Santiago del Estero&#41;&#59; Juan Jos&#233; Carmona&#44; N&#233;stor Tappari&#44; Andrea Morgenstern &#40;Hospital Madariaga&#44; Misiones&#41;&#59; Mar&#237;a ElinaTotaro &#40;Universidad Nacional de Misiones&#41;&#59; Enrique Berner&#44; Viviana Cramer&#44; Sandra V&#225;zquez&#44; Paula Real &#40;Hospital Argerich&#44; Buenos Aires&#41;&#44; Carlota Lopez Kaufman&#44; Gabriela Kosoy&#44; Luc&#237;a Katabian &#40;Hospital Rivadavia&#44; Buenos Aires&#41;&#59; Maria Silvia Severino &#40;Hospital Durand&#44; Buenos Aires&#41;&#46;</p>"
            "etiqueta" => "Appendix A"
            "titulo" => "MALBRAN HPV Surveillance Study Group"
            "identificador" => "sec0065"
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Prevalence&#44; with 95&#37; CI&#44; of all identified HPV types in non-vaccinated sexually active 15&#8211;17-year old girls from Argentina&#46;</p>"
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                  \t\t\t\t">106 &#40;11&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#40;9&#46;1&#8211;13&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">57 &#40;6&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#40;4&#46;4&#8211;7&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">145 &#40;15&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#40;12&#46;9&#8211;17&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>HPV 6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">64 &#40;6&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#40;5&#46;1&#8211;8&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>HPV 11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30 &#40;3&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#40;2&#46;0&#8211;4&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>HPV 6&#44; 11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">91 &#40;9&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#40;7&#46;6&#8211;11&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>HPV 6&#44; 11&#44; 16&#44; 18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">215 &#40;22&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#40;19&#46;8&#8211;25&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Nonavalent types&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>HPV 6&#44; 11&#44; 16&#44; 18&#44; 31&#44; 33&#44; 45&#44; 52&#44; 58&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">368 &#40;38&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#40;35&#46;4&#8211;41&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">HR vaccine and closely related types</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>HPV 16&#44; 18&#44; 31&#44; 33&#44; 45&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">237 &#40;24&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#40;22&#46;0&#8211;27&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>HPV 31&#44; 33&#44; 45&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">130 &#40;13&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#40;11&#46;4&#8211;15&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Alpha 9 species &#40;HPV 16&#44; 31&#44; 33&#44; 35&#44; 52&#44; 58&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">278 &#40;29&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#40;26&#46;2&#8211;32&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Alpha 9 species &#40;without HPV16&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">172 &#40;18&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#40;15&#46;5&#8211;20&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Alpha7 species &#40;HPV 18&#44; 39&#44; 45&#44; 59&#44; 68&#44; 70&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">169 &#40;17&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#40;15&#46;2&#8211;20&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Alpha 7 species &#40;without HPV 18&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">112 &#40;11&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#40;9&#46;7&#8211;13&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">HR types according to IARC criteria</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>HR-HPV13 types &#40;Group 1 and 2A&#41;<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">404 &#40;42&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#40;39&#46;1&#8211;45&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>HR-HPV 20 types &#40;Group 1&#44; 2A and 2B&#41;<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">455 &#40;47&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#40;44&#46;4&#8211;50&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>HR HPV 18 types &#40;Group 1&#44; 2A and 2B without HPV 16&#44;18&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">310 &#40;32&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#40;29&#46;4&#8211;35&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">LR types included and not included in the vaccine</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>HPV LR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">295 &#40;30&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#40;27&#46;9&#8211;33&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>HPV LR &#40;without HPV 6&#44;11&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">191 &#40;20&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#40;17&#46;4&#8211;22&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Group 1 IARC &#40;carcinogenic to humans&#41;&#58; HPV 16&#44; 18&#44; 31&#44; 33&#44; 35&#44; 39&#44; 45&#44; 51&#44; 52&#44; 56&#44; 58 and 59&#46; Group 2A IARC &#40;probably carcinogenic to humans&#41;&#58; HPV68&#46; Group 2B IARC &#40;possibly carcinogenic to humans&#41;&#58; HPV26&#44; 30&#44; 34&#44; 53&#44; 66&#44; 67&#44; 69&#44; 70&#44; 73&#44; 82&#44; 85 and 97&#46;</p>"
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                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td-with-role" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Sample collection city&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">HPV Positive</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">HPV16&#47;18</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">HPV6&#47;11&#47;16&#47;18</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">95&#37; CI &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">95&#37; CI &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">95&#37; CI &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Berazategui&#44; Province of Buenos Aires&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">272 &#40;28&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">117 &#40;43&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">37&#46;1&#8211;48&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25 &#40;9&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#46;8&#8211;12&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">43 &#40;15&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&#46;5&#8211;20&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Buenos Aires city&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">298 &#40;31&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">180 &#40;60&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">54&#46;8&#8211;65&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">47 &#40;15&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&#46;6&#8211;19&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">70 &#40;23&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18&#46;7&#8211;28&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Posadas&#44; Province of Misiones&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">172 &#40;18&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">106 &#40;61&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">54&#46;3&#8211;68&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">36 &#40;20&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&#46;8&#8211;27&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">47 &#40;27&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20&#46;7&#8211;34&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">La Banda&#44; Province of Santiago del Estero&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">215 &#40;22&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">136 &#40;63&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">56&#46;8&#8211;69&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">37 &#40;17&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&#46;2&#8211;22&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">55 &#40;25&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">19&#46;7&#8211;31&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2547154.png"
              ]
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          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Prevalence of HPV infection of any type&#44; HPV 16&#47;18&#44; and HPV 6&#47;11&#47;16&#47;18 by city of recruitment&#44; among sexually active non-vaccinated 15&#8211;17-year-old girls from Argentina&#46;</p>"
        ]
      ]
      3 => array:8 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at3"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td-with-role" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Single and Multiple infections&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Adolescents Tested &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>957&#41;</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">95&#37; CI &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 type&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">191 &#40;20&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#40;17&#46;4&#8211;22&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 types&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">137 &#40;14&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#40;12&#46;1&#8211;16&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 types&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">97 &#40;10&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#40;8&#46;2&#8211;12&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4 types&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">49 &#40;5&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#40;3&#46;7&#8211;6&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 or more types&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
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        "titulo" => "Acknowledgments"
        "texto" => "<p id="par0260" class="elsevierStylePara elsevierViewall">The authors sincerely thank all hospitals and institutions involved in the study from the following cities&#58; Berazategui &#40;Province of Buenos Aires&#41;&#44; Posadas &#40;Province of Misiones&#41;&#44; La Banda &#40;Province of Santiago del Estero&#41; and Buenos Aires&#44; and the girls who participated in this study for their generosity&#46;</p><p id="par0265" class="elsevierStylePara elsevierViewall">The authors are particularly grateful to the members of the Health Ministry of Santiago del Estero Province&#58; Minister&#44; Dr&#46; Luis Mart&#237;nez&#59; Undersecretary&#44; Dr&#46; Cesar Monti&#59; Executive Director CISB&#44; Dra&#46; Liliana Garnica&#59; Director of Maternity&#44; Childhood and Adolescence&#44; Dr&#46; Pedro Carrizo&#59; Director of Immunizations&#44; Dra&#46; Florencia Coronel&#59; Coordinator of the Cervical Cancer Program&#44; Dra&#46; Yolanda Mart&#237;nez&#59; APS Director&#44; Dra&#46; Teresa Santill&#225;n and <span class="elsevierStyleItalic">Unidades de ProntaAtenci&#243;n</span> &#40;UPAs&#41;&#59; USM Director&#44; Jos&#233; Alzogaray&#59; <span class="elsevierStyleItalic">Departamento de Docencia e Investigaci&#243;n</span>&#44; Dr&#46; Carlos Marrod&#225;n&#44; as well as to Dr&#46; Walter Villalba &#40;Director of the <span class="elsevierStyleItalic">Hospital Escuela de Agudos Ram&#243;n Madariaga</span>&#44; Posadas&#44; Misiones&#41;&#44; and Delia Dominga Motta &#40;nurse&#41;&#44; for their support and commitment in patient recruitment&#46;</p><p id="par0270" class="elsevierStylePara elsevierViewall">We are also indebted to Dr Enrique Lamuedra and Marcela Grosso &#40;<span class="elsevierStyleItalic">Centro Nacional de Red de Laboratorios</span>&#44; ANLIS - Malbr&#225;n&#41;&#44; for their assistance in sample transfer&#46;</p>"
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