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(B) Axial CT of the temporal bone and (C) coronal reconstruction from axial CT – showing hypoplastic tympanic cavity, absence of the ossicular chain, and atresia EAC.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Francisco Rosa, Miguel Bebiano Coutinho, João Pinto Ferreira, Cecilia Almeida Sousa" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Francisco" "apellidos" => "Rosa" ] 1 => array:2 [ "nombre" => "Miguel Bebiano" "apellidos" => "Coutinho" ] 2 => array:2 [ "nombre" => "João Pinto" "apellidos" => "Ferreira" ] 3 => array:2 [ "nombre" => "Cecilia Almeida" "apellidos" => "Sousa" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173573516300217?idApp=UINPBA00004N" "url" => "/21735735/0000006700000003/v1_201606140033/S2173573516300217/v1_201606140033/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S2173573516300102" "issn" => "21735735" "doi" => "10.1016/j.otoeng.2016.04.003" "estado" => "S300" "fechaPublicacion" => "2016-05-01" "aid" => "655" "copyright" => "Elsevier España, S.L.U. and Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Acta Otorrinolaringol Esp. 2016;67:130-4" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 1030 "formatos" => array:3 [ "EPUB" => 29 "HTML" => 660 "PDF" => 341 ] ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>" "titulo" => "HSP-90 Expression as a Predictor of Response to Radiotherapy in Head and Neck Cancer Patients" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "130" "paginaFinal" => "134" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Expresión de Heat Shock Protein-90 (HSP-90) como factor predictor de la respuesta a radioterapia en pacientes con tumores de cabeza y cuello" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1532 "Ancho" => 1626 "Tamanyo" => 138899 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">CRT classification tree to determine a cut-off point of HSP90AA levels with respect to the possibility of local relapse.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Jacinto García Lorenzo, Xavier León Vintró, Mercedes Camacho Pérez de Madrid" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Jacinto" "apellidos" => "García Lorenzo" ] 1 => array:2 [ "nombre" => "Xavier" "apellidos" => "León Vintró" ] 2 => array:2 [ "nombre" => "Mercedes" "apellidos" => "Camacho Pérez de Madrid" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0001651915000874" "doi" => "10.1016/j.otorri.2015.03.002" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0001651915000874?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173573516300102?idApp=UINPBA00004N" "url" => "/21735735/0000006700000003/v1_201606140033/S2173573516300102/v1_201606140033/en/main.assets" ] "en" => array:21 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>" "titulo" => "Oropharyngeal Perinatal Colonization by Human Papillomavirus" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "135" "paginaFinal" => "141" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "María Soledad Sánchez-Torices, Rocío Corrales-Millan, Jesús J. Hijona-Elosegui" "autores" => array:3 [ 0 => array:4 [ "nombre" => "María Soledad" "apellidos" => "Sánchez-Torices" "email" => array:1 [ 0 => "marisolsancheztorices@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Rocío" "apellidos" => "Corrales-Millan" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "Jesús J." "apellidos" => "Hijona-Elosegui" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Servicio de Otorrinolaringología, Complejo Hospitalario de Jaén, Jaén, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Ginecología y Obstetricia, Complejo Hospitalario de Jaén, Jaén, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Colonización orofaríngea perinatal por el virus del papiloma humano" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1011 "Ancho" => 1489 "Tamanyo" => 99960 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Number of isolates per HPV serotype isolated in samples of maternal cervical secretions.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Human papilloma virus infection (HPV) is the most common human sexually transmitted disease.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">1</span></a> Although information on this infection is very heterogeneous, it is estimated that between 80% and 90% of the population will come into contact with HPV in their lifetime.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">1</span></a> The infection mechanism for most of these cases is associated with the participation of the individual in sexual practices of varying types, however, there is currently solid and growing scientific evidence to indicate that the infection might be acquired through other routes which are not necessarily linked to sexual contact.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">2</span></a> One of these routes is mother-to-child transmission, either during gestation or at the time of delivery.</p><p id="par0010" class="elsevierStylePara elsevierViewall">HPV infection is clinically relevant because the condition is a cause of epithelial cancer of the cervix (and other neoplastic and dysplastic lesions of the anogenital region) and is also closely associated with the appearance of tumours and various benign and malignant lesions in the head and neck whose clinical behaviour, even in “histologically benign” situations can be fatal for the patient; such as respiratory papillomatosis for example, which can cause a severe obstruction in the airway.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">3</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Despite the above, our current knowledge about the clinical implications of congenital HPV infection, its possible transmission routes to the newborn and the theoretical role of maternal immunisation against HPV (primary or secondary) is very limited.</p><p id="par0020" class="elsevierStylePara elsevierViewall">This research study seeks to investigate in depth mother-to-foetus transmission of HPV and provide information about its frequency and mechanism in our environment. Very little research has been undertaken into this aspect to date.</p><p id="par0025" class="elsevierStylePara elsevierViewall">The principal objective is to establish the rate of oropharyngeal neonatal HPV colonization in vaginal deliveries from asymptomatic, immunocompetent mothers carrying the virus in their lower genital tract at the time of delivery.</p><p id="par0030" class="elsevierStylePara elsevierViewall">As a secondary objective we aim to establish the amount of oropharyngeal colonizations which are not exclusively attributable to the passage of the foetus through the birth canal, as there is evidence of possible transmission via the placenta.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">4</span></a></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Methodology</span><p id="par0035" class="elsevierStylePara elsevierViewall">In order to achieve the abovementioned objectives, the presence and type of viral HPV DNA was determined at the time of delivery in samples obtained from maternal cervical secretions, amniotic fluid, venous blood from the umbilical cord, and from the newborns’ oropharynx.</p><p id="par0040" class="elsevierStylePara elsevierViewall">All the pregnant women attended in our centre during the first six months of 2014 were chosen as possible candidates, provided they met each of the following conditions:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">-</span><p id="par0045" class="elsevierStylePara elsevierViewall">A history of a positive Hybrid Capture test (HC2 Digene<span class="elsevierStyleSup">®</span> marketed by Qiagen) from the cervical cancer screening programme, provided this test had been undertaken in the 12 months immediately preceding the time of observation. This would enable the cost of the investigation to be rationalised, selecting pregnant women with a higher risk of active HPV at the time of delivery from the possible candidates for the study.</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">-</span><p id="par0050" class="elsevierStylePara elsevierViewall">No organic lesions associated with HPV infection in the soft birth canal. At the moment, it is not known whether the presence of a histological lesion in the genital tract implies different viral behaviour or reduced immunological competence compared to the cases where there is colonization by HPV alone. Even so, it appears logical to suppose that women with cervical dysplasia secondary to HPV infection would have a deficient immunological pattern, as only a small proportion of women infected by HPV develop clinical lesions in their genital tract.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">1</span></a> For this reason, it was decided that these cases should be excluded from the study.</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">-</span><p id="par0055" class="elsevierStylePara elsevierViewall">Maternal age over 35. This made it possible to establish that maternal HPV could be appropriately contextualised within our current programme of cervical screening. At present all the screening programmes for the disease associated with HPV advise that it should be detected and typified using molecular techniques when the mother is aged over 30–35, because the viral clearance rate before this age is very high and, therefore, identifying HPV in the female genital tract is of little diagnostic or preventive value.</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">-</span><p id="par0060" class="elsevierStylePara elsevierViewall">Gestational age above 37 weeks (correctly dated by early ultrasound). Prematurity is a major risk factor in terms of neonatal predisposition to the infection.</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">-</span><p id="par0065" class="elsevierStylePara elsevierViewall">Proposed elective induction of vaginal delivery (for obstetric reasons other than premature rupture of membranes). The fact that cases with premature rupture of membranes will be covered later, in the section on exclusion criteria.</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">-</span><p id="par0070" class="elsevierStylePara elsevierViewall">Pregnant women who, once appropriately informed of the purpose, procedure and implications of the study freely and voluntarily agreed to take part. They were assured that their acceptance or refusal to participate would not alter the clinical care that they would receive during their labour.</p></li></ul></p><p id="par0075" class="elsevierStylePara elsevierViewall">The following were considered exclusion criteria for possible candidates in the study:<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">-</span><p id="par0080" class="elsevierStylePara elsevierViewall">Pregnancies complicated by premature rupture of membranes, or by oligohydramnios whose aetiology would not rule out this situation. This would prevent bias or confounding factors associated with possible HPV neonatal colonization through the “ascending” route via the genital tract or via a “wash effect” of hydrorrhea on HPV colonization in the genital tract.</p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">-</span><p id="par0085" class="elsevierStylePara elsevierViewall">Pregnant women with diseases or therapies causing immunosuppression or which might change the cycle of viral cell replication.</p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">-</span><p id="par0090" class="elsevierStylePara elsevierViewall">Pregnant women treated using invasive procedures for the diagnosis or prenatal treatment of congenital anomalies (in these women the premature rupture of amniotic fluid membranes might act as a confounding factor).</p></li><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">-</span><p id="par0095" class="elsevierStylePara elsevierViewall">Pregnant women treated by elective caesarean (in these cases, obviously, the newborn would not pass through the birth canal).</p></li><li class="elsevierStyleListItem" id="lsti0055"><span class="elsevierStyleLabel">-</span><p id="par0100" class="elsevierStylePara elsevierViewall">The cases where incomplete or deficient observations were carried out, because the data collection process was not applied to the guide that we shall explain later, or due to a loss of data which would imply incomplete observations of the cases studied. Included in this scenario were births where the newborn was not delivered vaginally (in other words, in pregnant women treated by non-elective caesarean section for any reason in the context of the induction of their labour).</p></li></ul></p><p id="par0105" class="elsevierStylePara elsevierViewall">The sample collection procedure is summarised as follows:</p><p id="par0110" class="elsevierStylePara elsevierViewall">Firstly, a sample of maternal endocervical secretion was taken using a sterile speculum from each of the pregnant women during the latent stage of their labour, before the membranes ruptured.</p><p id="par0115" class="elsevierStylePara elsevierViewall">Subsequently, a sample of amniotic fluid was taken by artificial rupture of membranes during the induction of labour, guided and protected from possible cervico-vaginal contamination by introducing a rigid and sterile transcervical amnioscope. A sterile lancet was entered through said canal to artificially rupture the membranes, disregarding the first parts of hydrorrhea thus preventing contamination of the amniotic fluid by cervico-vaginal HPV.</p><p id="par0120" class="elsevierStylePara elsevierViewall">Once the foetus had been delivered vaginally, a sample of umbilical venous blood was taken from each patient to detect HPV DNA at that level. Prior to this the cord was clamped and its surface cleaned with sterile solution (at the site to be punctured for the sample to be taken). The reason for taking a sample from the umbilical vein and not from one of the two arteries of the cord is because at intrauterine level the umbilical vein acts like an “artery” which perfuses the foetus and is therefore the optimal site for detecting mother-to-foetus haematogenous spread of HPV.</p><p id="par0125" class="elsevierStylePara elsevierViewall">Finally, a sample was taken of the newborn's oropharyngeal secretions minutes after birth. This procedure was repeated between 7 and 10 days after birth.</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Material and Methods: Procedure for Samples and Statistical Treatment</span><p id="par0130" class="elsevierStylePara elsevierViewall">In all cases, the samples were taken using sterile material (swabs, needles and syringes), following the recommendations of the Microbiology Department in charge of identifying and typing the HPV, for the transport and processing of the samples (PCR molecular techniques with microarrays were used to establish the presence or absence of viral DNA in each of the samples and the viral serotypes matching said DNA). To be specific, standard GP5+/GP6+ PCR were used and EIA enzymatic immunoassay.</p><p id="par0135" class="elsevierStylePara elsevierViewall">The identification, processing and custody of the samples were appropriately monitored, both in the laboratory and during the statistical treatment phase, under the data protection and statistical confidentiality act which is currently in force in our centre.</p><p id="par0140" class="elsevierStylePara elsevierViewall">The entire design and implementation phase of the research was monitored by a methodology and statistical analysis specialist who had no connection with the work group. Similarly, the entire process was approved by our centre's Research Ethics Committee.</p></span></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Results</span><p id="par0145" class="elsevierStylePara elsevierViewall">Of the 97 pregnant women who were candidates for the study and who were asked to participate in the research, 95 agreed to take part in the trial. Four of these women were excluded due to incomplete observations. Ninety-one patients took part in the end.</p><p id="par0150" class="elsevierStylePara elsevierViewall">With regard to the vaccination status of the series, only three of the pregnant women had received one or more vaccinations against HPV at the time of observation, one of them had been given the tetravalent vaccination (one dose) and the other 2 the bivalent (one had received the 3 doses and the other had received 2). None of the women studied had received a different type of vaccination for primary immunisation against HPV not marketed in Spain.</p><p id="par0155" class="elsevierStylePara elsevierViewall">HPV DNA was positively detected in the maternal cervical secretions at the time of delivery in 90 of the 91 cases (98.90%), and 11 cases of colonization of 3 or more serotypes were encountered simultaneously (meaning 12.22% of the total patients colonized).</p><p id="par0160" class="elsevierStylePara elsevierViewall">It was possible to make 129 serum isolates of HPV in the 90 pregnant women, corresponding to 13 different serotypes. The most frequently isolated were: 16, 6, 18, 11, 31, 33, 35, 38 and 52 (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0165" class="elsevierStylePara elsevierViewall">Viral DNA was isolated in 9 cases of the samples of amniotic fluid (which was 10% of the patients whose lower genital tract was colonized), whereas this rate of isolation did not reach 7% in the samples of umbilical venous blood (viral DNA was identified in 6 cases only).</p><p id="par0170" class="elsevierStylePara elsevierViewall">All the cases which were positive for HPV DNA in umbilical venous blood were also positive in amniotic fluid, with complete concordance with regard to the serotypes isolated in each medium (in number and type). This did not occur with regard to maternal cervical HPV colonization. In 8 of the 9 cases the serotypes present in amniotic fluid were also present in the maternal endocervix, whereas there was one case of “intrauterine” serotype 35 isolate (in umbilical blood and amniotic fluid also) which did not coexist with a simultaneous maternal colonization in the cervix. There were 3 cases where not all the serotypes present in the cervix were detected in either the amniotic fluid or in the umbilical blood. All these were cases of multiple cervical colonizations by at least 3 serotypes.</p><p id="par0175" class="elsevierStylePara elsevierViewall">The amniotic colonizations were by serotypes 6, 16, 18 and 35. Six cases had a single colonization (3 cases by serotype 16, 2 by 6 and one by 18); and 3 were colonized by 2 serotypes (one case by 16 and 18, one by 6 and 35, and one by 6 and 40).</p><p id="par0180" class="elsevierStylePara elsevierViewall">With regard to neonatal oropharyngeal HPV colonization, the virus was isolated in 53 of the 91 new born infants (58.24%) in the time immediately after delivery (one was a twin birth). The most frequently isolated serotypes had a distribution of proportionality which was very similar, although not identical, to that found in the maternal endocervix.</p><p id="par0185" class="elsevierStylePara elsevierViewall">Although the case-by-case concurrence between the results obtained from the maternal endocervix and the neonatal pharynx was high, in 9 of the 53 cases there were differences between the maternal cervix and the neonatal oropharynx in terms of the number of isolated serotypes. There was no oropharyngeal colonization in the aforementioned isolated case of intrauterine colonization by HPV serotype 35 with no concomitant maternal endocervical colonization by this serotype.</p><p id="par0190" class="elsevierStylePara elsevierViewall">If 129 HPV serotypes were isolated in the endocervical samples (total number of isolates in the entire group of women studied), 83 colonizations were identified in the oropharyngeal samples, so that there were 46 fewer isolates corresponding to:<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0060"><span class="elsevierStyleLabel">-</span><p id="par0195" class="elsevierStylePara elsevierViewall">38 single maternal endocervical colonizations which were not identified in the newborn infant.</p></li><li class="elsevierStyleListItem" id="lsti0065"><span class="elsevierStyleLabel">-</span><p id="par0200" class="elsevierStylePara elsevierViewall">3 cases of maternal cervical colonization by 2 HPV serotypes of which only one serotype could be identified in the newborn infant (in 2 cases the serotype which was not detected was 16 and in one it was 6).</p></li><li class="elsevierStyleListItem" id="lsti0070"><span class="elsevierStyleLabel">-</span><p id="par0205" class="elsevierStylePara elsevierViewall">5 cases of multiple maternal endocervical colonization (by 3 or more serotypes simultaneously) for which a parallel neonatal colonization by all the maternal strains could not be found (the serotypes were 6, 11, 38 and 2 cases of 33).</p></li></ul></p><p id="par0210" class="elsevierStylePara elsevierViewall">Finally, with regard to neonatal pharyngeal HPV colonization 7–10 days after birth, of the 53 newborns identified as “colonized/infected” at birth, only 27 maintained this condition after this length of time had passed (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>).</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0215" class="elsevierStylePara elsevierViewall">Forty-seven isolates of HPV serotype were found in 27 newborn infants (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>).</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0220" class="elsevierStylePara elsevierViewall">With regard to the initial neonatal testing, performed in the minutes immediately following birth, there were 26 cases of clearance (49.05%), corresponding to newborn infants infected by 2 or fewer HPV serotypes simultaneously (21 of the 26 cases) and by serotypes other than 6, 11, 16 and 18 (23 of the 27 cases).</p><p id="par0225" class="elsevierStylePara elsevierViewall">The oropharyngeal clearance rate after 7–10 days in the subgroup of newborn infants with a history of amniotic and umbilical HPV colonization was 44.45%.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Discussion</span><p id="par0230" class="elsevierStylePara elsevierViewall">Although HPV colonization is considered the most common human sexually transmitted disease,<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">1</span></a> for years there has been solid evidence to suggest the possibility that this infection might be acquired by mechanisms that are not linked to sexual contact.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">2</span></a> One of these is mother-to-child transmission, either during gestation or at the time of delivery.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">2</span></a></p><p id="par0235" class="elsevierStylePara elsevierViewall">Many of the aspects in relation to perinatal HPV infection are still not known; for example, the frequency of mother-to-child transmission, its ultimate transference mechanism and especially its clinical implications in both the infancy and adulthood of colonized newborns.</p><p id="par0240" class="elsevierStylePara elsevierViewall">Discovering whether the presence of HPV in the newborn infant delivered vaginally is simple contamination by maternal secretions or a true neonatal infection is not an easy task. Some authors have tried to clarify this by undertaking microbiological studies of the foetus, amniotic fluid, the placenta and the membranes surrounding it before the amniotic sac ruptures and performing a caesarean in sterile conditions. This approach, in the clinical context that concerns us, is not acceptable, as the morbidity associated with an abdominal delivery is clearly higher than that of a vaginal birth and therefore it is neither ethical nor acceptable to perform caesareans to prevent possible contaminations of biological samples, however attractive it might appear for the purposes of our investigation. Furthermore, the study of a vaginal delivery as a source of neonatal HPV infection is in itself a matter of great scientific interest.</p><p id="par0245" class="elsevierStylePara elsevierViewall">There have been a great many methods used to study the maternal–foetal transmission of HPV. With inclusion criteria, study objectives and strategies so varied that it is very difficult to extrapolate the information extracted from each series to means other than those studied. It is possible that they cannot not even be extrapolated to other clinical contexts, given the wide source of biases and confounding factors that each design has to assume.</p><p id="par0250" class="elsevierStylePara elsevierViewall">The main purpose of our research was to establish the rate of oropharyngeal neonatal HPV colonization in vaginal deliveries from immunocompetent mothers, carriers of the virus in their lower genital tract at the time of birth. Our results showed a theoretical intrapartum transmission rate of 58.24%. Obviously this information requires some consideration: firstly, finding HPV in the neonatal oropharynx does not necessarily imply that this colonization is the unequivocal result of intrapartum contamination. In fact, there is evidence in the literature and also in one case of our series that HPV colonization does not always respond to a physical transvaginal mechanism.<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">1,5</span></a></p><p id="par0255" class="elsevierStylePara elsevierViewall">Furthermore, the fact that a certain viral serotype cannot be found in a biological sample is not proof that it is not present in that sample; even so this possible bias, unavoidable but unlikely given the reliability of the currently available molecular techniques is equally probable in any samples (endocervical, oropharyngeal, umbilical…). Therefore we have to assume that the results obtained from molecular analysis of each of the samples studied are highly representative of the real situation of HPV colonization.</p><p id="par0260" class="elsevierStylePara elsevierViewall">Our data indicate that the mother-to-newborn mechanism of HPV contamination is essentially, but not exclusively, transvaginal. One of the main limitations of our design is the assumption that the samples obtained from amniotic fluid and umbilical venous blood are representative. The method followed for this purpose is not infallible, since at the time the samples were taken there might have been inadvertent contamination from maternal cervico-vaginal secretion. But taking a better quality sample, i.e., before the newborn passes through the birth canal, would mean using invasive intrauterine techniques on the pregnant women studied (amniocentesis and cordocentesis) which we consider unjustifiable, because they would offer no benefit at all to the mother or the foetus and result in increased perinatal morbimortality due to the intra-amniotic aggression which both procedures involve.</p><p id="par0265" class="elsevierStylePara elsevierViewall">It is possible, therefore, that a sample contaminated by maternal genital secretions might give higher rates of mother-to-foetus transvaginal transmission of HPV than the real rates. However the possibility cannot be ruled out that the rate we found in our series is a true reflection of the real maternal–foetal transmission rate of HPV. In this regard, the methodology used in our research makes us optimistic that the samples obtained are representative. To our knowledge there is no other more reliable design than that proposed and applied in our series, and therefore, we consider that it should be considered the most thorough and applicable perinatal HPV screening and typing procedure in daily clinical practice.</p><p id="par0270" class="elsevierStylePara elsevierViewall">The rates of intrapartum transmission of HPV referred to in the literature are very conflicting<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">1,5</span></a> and vary from somewhat more than 5% to near 70%. However the broadest and better designed series (and those that use a methodology closer to that used in our series and based on the study of asymptomatic women) achieve rates close<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">6</span></a> to our 58.24%. These rates are, in general, lower for newborns delivered by caesarean, but there does not appear to be sufficiently sold data at the moment to recommend that this technique should be performed prophylactically in mothers who are carriers of HPV in their lower genital tract at the time of delivery.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">7</span></a> The only exceptions to this rule are cases with extensive genital warts (vaginal or introital) blocking the birth canal and which might involve a high risk of maternal perineal injury with high associated neonatal infectivity.</p><p id="par0275" class="elsevierStylePara elsevierViewall">As highlighted earlier, our data indicate mother-to-foetus transmission of HPV which is eminently transvaginal. But there is evidence that, at least in theory, there are 3 other different maternal–foetal transmission mechanisms: ascending intra-uterine, haematological and via the placenta/trophoblastic.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">1</span></a> Some authors even suggest transmission from the early developmental stages of the embryo, probably secondary to HPV transmission through semen. In fact, the seminal lavage techniques currently used in assisted reproductive technology do not manage to completely eliminate HPV colonization of the samples.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">8</span></a></p><p id="par0280" class="elsevierStylePara elsevierViewall">With regard to our methodology, the possibility that there are cases of premature rupture of amniotic membranes which have not been diagnosed due to an absence of symptoms and which can be a source of bias, either because they mask an ascending feto-neonatal colonization, or because there is a continuous, but imperceptible loss of amniotic fluid, producing a mechanical effect of washing the maternal genital tract which makes it difficult to identify HPV. Both conditions appear improbable, in that a continuous loss of amniotic membrane solution with so few symptoms would be unlikely to be large enough to allow germs to ascend with ease into the uterine cavity and the existence of a hydrorrhoea capable of dragging through all the HPV present in the mother's lower genital tract is even less likely.</p><p id="par0285" class="elsevierStylePara elsevierViewall">An unknown yet to be resolved is the real relevance of neonatal contamination by HPV. It is highly likely that good part of these colonizations are transitory and irrelevant, given the current burden of perinatal disease which can be put down to HPV.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">1</span></a> In our series, the rate of colonization was reduced practically by half in only 10 days, which implies that a good part of the cases of infection or colonization were transitory. Even so, this does not diminish the importance of the process, because the potential repercussions of HPV infection acquired during the perinatal phase are extremely serious. The data relating to neonatal colonization by HPV a year from birth are yet to be presented. This analysis, although yet to be made, could provide important information on the persistence of vertical infection by HPV in infancy.</p><p id="par0290" class="elsevierStylePara elsevierViewall">One of the factors which might justify the findings of our series is the strict association between pregnancy and the prevalence of HPV infection, which increases on average from 8% to 23% from the first to the third trimester of pregnancy.<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">9</span></a> Some authors argue the role of physiological immunosuppression during pregnancy as an essential factor in HPV transmission, overriding other obstetric factors (including the type of delivery).<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">10</span></a></p><p id="par0295" class="elsevierStylePara elsevierViewall">The clinical implications of neonatal infection by HPV go beyond the area of ENT. In fact, there are recent data which appear to associate HPV infection with some obstetric disorders such as delayed intrauterine growth and spontaneous abortion<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">11</span></a>; or with skin and eye disorders.<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">12</span></a></p><p id="par0300" class="elsevierStylePara elsevierViewall">Finally, it is relevant to note that the distribution of HPV serotypes in our series follows the traditionally reported epidemiological patterns for the lower female genital tract in our environment, and serotypes 6, 11, 16 and 18 are particularly prevalent in the tract (the serotypes included in the vaccinations which are currently marketed in our country).</p><p id="par0305" class="elsevierStylePara elsevierViewall">The prophylactic potential of primary immunisation against HPV with regard to maternal–foetal transmission of HPV and its associated disease is not known. More research is necessary in this regard,<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">13</span></a> although there is evidence of transference through the placenta of antibodies against the virus, and of the major preventive role of HPV vaccination against tumour disease of the genital tract.<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">13</span></a> The coverage potential offered by immunisation against HPV serotypes 6, 11, 16 and 18 (those that are included in the currently marketed vaccinations in our country) is extremely high, in view of the distribution of HPV amongst newborns carrying the virus 10 days after delivery (91.48% carry these serotypes). In any case, it should not be forgotten that there might be frequent and spontaneous viral clearance in a high proportion of cases.<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">13</span></a></p><p id="par0310" class="elsevierStylePara elsevierViewall">In any case, the fact should not be ignored that it is biologically plausible that there is a period of viral latency in which it is impossible to detect the presence of DNA. This makes it impossible to ascertain whether this situation applies to individuals who are not infected and immune, to patients who are susceptible but not infected or, simply, to patients who are infected.<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">14</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Conflict of Interests</span><p id="par0315" class="elsevierStylePara elsevierViewall">The authors have no conflict of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres673024" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction and objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Method" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec679372" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres673023" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción y objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Método" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec679371" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Methodology" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Material and Methods: Procedure for Samples and Statistical Treatment" ] ] ] 6 => array:2 [ "identificador" => "sec0020" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0025" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0030" "titulo" => "Conflict of Interests" ] 9 => array:2 [ "identificador" => "xack227181" "titulo" => "Acknowledgements" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2014-12-16" "fechaAceptado" => "2015-05-03" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec679372" "palabras" => array:4 [ 0 => "Human papillomavirus" 1 => "Delivery" 2 => "Neonatal" 3 => "Oropharynx" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec679371" "palabras" => array:4 [ 0 => "Virus del papiloma humano" 1 => "Parto" 2 => "Neonatal" 3 => "Orofaringe" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction and objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Human papillomavirus (HPV) infection is the most common human sexually transmitted disease. It is clinically relevant because this condition is necessary for the development of epithelial cervical cancer, and it is also a factor closely associated with the occurrence of diverse tumours and various benign and malignant lesions of the head and neck area. The infective mechanism in most of these cases is associated with sexual intercourse, but there is recent scientific evidence suggesting that HPV infection may also be acquired by other routes of infection not necessarily linked to sexual contact. One of them is vertical transmission from mother to child, either during pregnancy or at the time of delivery.</p><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">The aim of our research was to study maternal–foetal HPV transmission during childbirth in detail, establishing the rate of oropharyngeal neonatal HPV in vaginal deliveries.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Method</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">The presence and type of HPV viral DNA at the time of delivery in samples of maternal cervical secretions, amniotic fluid, venous cord blood samples and neonatal oropharynx in pregnant women (and their babies) were determined.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">The rate of oropharyngeal neonatal HPV colonization in vaginal deliveries was 58.24%.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">The maternal and neonatal HPV colonization mechanism is essentially, but not exclusively, transvaginal.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction and objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Method" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducción y objetivo</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">La infección por el virus del papiloma humano (VPH) es la enfermedad de transmisión sexual más frecuente del ser humano. Su relevancia clínica radica en que tal condición es causa necesaria para el desarrollo de cáncer epitelial de cuello uterino y también un factor estrechamente asociado a la aparición de tumores y diversas lesiones benignas y malignas del área cráneo-cervical. El mecanismo infectivo para la mayoría de estos casos está asociado a la participación del individuo en prácticas sexuales de diverso tipo, pero existen en la actualidad evidencias científicas que indican la posibilidad de que dicha infección pueda ser también adquirida por otras vías de contagio no necesariamente ligadas al contacto sexual. Una de ellas es la transmisión desde la madre al hijo, bien durante la gestación, bien en el momento del parto.</p><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">El objetivo de nuestra investigación es profundizar en el estudio de la transmisión materno-foetal de VPH durante el parto, estableciendo la tasa de colonización orofaríngea neonatal por VPH en los partos vaginales.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Método</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Se determinó la presencia y tipo de ADN viral de VPH en el momento del parto en las muestras obtenidas de las secreciones cervicales maternas, líquido amniótico, sangre venosa de cordón y orofaringe neonatal en las embarazadas (y sus recién nacidos).</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">La tasa de colonización orofaríngea neonatal por VPH en los partos vaginales de madres inmunocompetentes portadoras del germen fue del 58,24%.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">El mecanismo de contaminación materno-neonatal por VPH es esencialmente, que no exclusivamente, transvaginal.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción y objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Método" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Sánchez-Torices MS, Corrales-Millan R, Hijona-Elosegui JJ. Colonización orofaríngea perinatal por el virus del papiloma humano. Acta Otorrinolaringol Esp. 2016;67:135–141.</p>" ] ] "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1011 "Ancho" => 1489 "Tamanyo" => 99960 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Number of isolates per HPV serotype isolated in samples of maternal cervical secretions.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 845 "Ancho" => 1606 "Tamanyo" => 59670 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Rate of neonatal oropharyngeal colonization by HPV in the immediate postpartum and at 7–10 days.</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1109 "Ancho" => 1542 "Tamanyo" => 88039 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Distribution of the HPV serotypes isolated in the neonatal oropharynx in the 7–10 days after delivery.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:14 [ 0 => array:3 [ "identificador" => "bib0075" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Human papillomavirus vertical transmission: review of current data" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "A.C. 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Oropharyngeal Perinatal Colonization by Human Papillomavirus
Colonización orofaríngea perinatal por el virus del papiloma humano