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Human Papillomavirus Genotypes Present in the Oral Mucosa of Newborns and their Concordance with Maternal Cervical Human Papillomavirus Genotypes
Abstract
To elucidate the concordance of human papillomavirus (HPV) genotypes between the mother and her newborn and to identify risk factors for the vertical transmission of HPV.
HPV genotypes present in 329 pregnant women, their newborns, cord blood, and placenta samples were determined by molecular techniques, including using pure DNA for nested polymerase chain reaction. HPV antibodies were tested using multiplex HPV serology. Kappa statistics and the Wilcoxon test were used to assess concordance, and regression analysis was used to calculate ORs and 95% CIs.
HPV DNA was detected in 17.9% of oral samples from newborns and in 16.4% of the cervical samples of the mothers. At delivery, mother-newborn pairs had similar HPV-genotype profiles, but this concordance disappeared in 2 months. Oral HPV carriage in newborns was most significantly associated with the detection of HPV in the placenta (OR=14.0; 95% CI, 3.7-52.2; P=.0001). The association between status of the cord blood and oral HPV was also significant at delivery (OR=4.7; 95% CI, 1.4-15.9; P=.015) but disappeared within 1 month. HPV antibodies in infants were of maternal origin (OR=68; 95% CI, 20.1-230.9; P=.0001).
HPV is prevalent in oral samples from newborns. The genotype profile of newborns was more restricted than that of the maternal cervical samples. The close maternal-newborn concordance could indicate that an infected mother transmits HPV to her newborn via the placenta or cord blood.
... Perinatal transmission has been regarded as the most likely explanation for HPV detection in newborns. Several studies have shown that children born to HPV-positive mothers have a higher risk of becoming HPV positive (9)(10)(11)(12)(13)(14). Meta-analysis of 3,128 mother-child pairs showed that children born to HPV-positive mothers were 33% more likely to be HPV positive than children born to HPV-negative mothers (6). ...
... The Finnish Family HPV Study is a prospective cohort study conducted at the University of Turku and Turku University Hospital, Turku, Finland, since 1998. Members of 329 families were enrolled (329 mothers, 131 fathers, and 331 newborns) as described (13,14,18). Women were enrolled at a minimum of 36 weeks of their index pregnancy and subsequently followed up for 6 years. ...
... For persistence, a generalized estimating equation (GEE) modeling was used. In the univariate GEE model, all covariates recorded at baseline and previously implicated as potential risk factors for HPV infections were tested (13,14). The following risk factors were analyzed for the both parents: age; age at time of first sexual encounter; number of lifetime sexual partners; smoking; use of alcohol; history of skin warts, oral/genital warts, and papillomas; history of sexually transmitted infections; drug consumption; oral and genital HPV DNA status; and HPV serologic results at baseline before the birth of the index child. ...
Human papillomavirus (HPV) infections are found in children, but transmission modes and outcomes are incompletely understood. We evaluated oral samples from 331 children in Finland who participated in the Finnish Family HPV Study from birth during 9 follow-up visits (mean time 51.9 months). We tested samples for 24 HPV genotypes. Oral HPV prevalence for children varied from 8.7% (at a 36-month visit) to 22.8% (at birth), and 18 HPV genotypes were identified. HPV16 was the most prevalent type to persist, followed by HPV18, HPV33, and HPV6. Persistent, oral, high-risk HPV infection for children was associated with oral HPV carriage of the mother at birth and seroconversion of the mother to high-risk HPV during follow-up (odds ratio 1.60-1.92, 95% CI 1.02-2.74). Children acquire their first oral HPV infection at an early age. The HPV status of the mother has a major impact on the outcome of oral HPV persistence for her offspring.
... The PCR system used for alpha HPV detection was evaluated for its sensitivity and specificity for individual HPV genotypes using a proficiency panel of HPV recombinant plasmids obtained in the context of the 4 th WHO HPV LabNet Proficiency Study for Evaluating HPV DNA Typing Methods. The system was evaluated as proficient for detection of HPV 16,18,31,33,35,39,45,52,56, 58, 59, 66, and 68b (http://www.who.int), being able to detect 50 genome equivalents (GE)/5 μL of HPV 16 and HPV 18 DNA, and 500 GE/5 μL of the other HPV genotypes with a specificity above 97%. ...
... Alpha HPVs show a higher prevalence in vaginal/cervico-vaginal, oral, placental maternal samples, as well as in the peripheral blood of the mother, in the prepartum and in the peripartum period (Table S2). Two studies included in the meta-analysis [44,45] showed the presence of alpha HPV in breast milk during the postpartum period. Louvanto et al., reported no association between the HPV genotypes found in the mothers and those found in the oral mucosa of infants [44]; furthermore, Yoshida et al. did not find any concordance between HPV genotypes in the breast milk and those present in the newborns [12]. ...
... Louvanto et al., reported no association between the HPV genotypes found in the mothers and those found in the oral mucosa of infants [44]; furthermore, Yoshida et al. did not find any concordance between HPV genotypes in the breast milk and those present in the newborns [12]. Conversely, Koskimaa et al., observed a significant concordance between the HPV genotypes suggestive of viral transmission from the mother's epithelium to the oral cavity of the infant [45]. In one of the above mentioned studies [23] the most prevalent HPVs in nipple samples were genotypes 6 and 11, followed by others types such as HPV 16,57,27,66,37,20,21,23,32,38. ...
Vertical transmission of human papillomaviruses (HPVs) from mother to infant is known to occur during labor, delivery or breastfeeding. Infection with mucosal HPV 6 and 11 may cause recurrent respiratory papillomatosis in children, which is a rare and severe respiratory disease. The cutaneous HPV genotypes have also been described to be transmitted from mother to newborn through skin-to-skin contacts and during breastfeeding. To investigate the perinatal transmission of alpha and beta HPVs we collected nasopharyngeal specimens from 0–12-months-old infants born by vaginal delivery and breastfed at the time of sample collection. The mucosal and cutaneous HPVs were searched by nested PCR using the MY09/11-MGPs and CP65/70-CP66/69 primer sets, respectively, and genotypes identified by direct sequencing analysis. Fourteen out of 113 (12.4%) samples tested positive for HPV and sequence analysis allowed us to identify eight beta genotypes (HPV 5b, 20, 25, 100, 107, 124, 152 and RTRX7). Moreover, we performed a comprehensive review of published studies on the prevalence of mucosal and cutaneous HPVs among 5126 newborns and observed that 10% and 53% were positive for alpha and beta HPVs, respectively. In all studies there was an inverse correlation between the rate of alpha HPV positivity and age, while a significant positive trend was observed in beta HPV detection and age with the highest rate among children older than 12 months (Χ2 test for trend of 10.6, p < 0.001). Further studies are needed to confirm the hypothesis that beta HPVs are transmitted to breastfeeding infants through shedding of viruses in the breast milk or on the external breast epithelium.
... HPV DNA was extracted by the high-salt method as described in Miller [27] et al. (1988). HPV genotyping was performed by Multimetrix (Progen Biotechnik GmbH, Heidelberg, Germany) as described in Koskimaa [28] et al.(2012) and Louvanto [11] et al. (2017). The HPV genotypes of all of the samples has been analyzed and reported earlier from infant oral [28] and from breast milk [11]. ...
... HPV genotyping was performed by Multimetrix (Progen Biotechnik GmbH, Heidelberg, Germany) as described in Koskimaa [28] et al.(2012) and Louvanto [11] et al. (2017). The HPV genotypes of all of the samples has been analyzed and reported earlier from infant oral [28] and from breast milk [11]. ...
... The HPV status of the complete Finnish family HPV study samples has been previously reported by Koskimaa [28] et al. (2012) and Louvanto [11] et al. (2017). In the present sub cohort of 31 mother-infant pairs, HPV DNA was detected in 8.6% of the mother's breast milk and 40% of the infant oral samples. ...
Objective
We investigated the association between bacterial microbiota in breast milk and the infant mouth. The influence of human papilloma virus (HPV) infection on infant oral microbiota was also assessed.
Material and methods
Altogether 35 breast milk and 35 infant oral samples with known HPV status were selected from the Finnish Family HPV Study cohort. In total, there were 31 mother-infant pairs. The microbiota composition was characterized by 16S rRNA gene sequencing (V3-V4 region).
Results
HPV DNA was present in 8.6% (3/35) of the breast milk and 40% (14/35) of the infant oral samples. Eight shared genera between breast milk and infant oral were found; these included Streptococcus, Staphylococcus, Unclassified Gemellaceae, Rothia, Veillonella, Haemophilus, Propionibacterium and Corynebacterium. HPV status was not associated with either microbiota richness or diversity in the infant mouth. However, the infant oral microbiota clustered in different groups according to HPV status. We detected higher abundance of Veillonella dispar (p = 0.048) at species level in HPV negative infant oral samples. We did not detect differences in the breast milk microbiota composition related to HPV infection due to only three HPV positive milk samples.
Conclusions
HPV infection is associated with distinct oral bacterial microbiota composition in infants. The direction of causality underlying the phenomenon remains unclear.
... HPV has long been regarded mainly as a sexually transmitted disease (STD) but recent studies have shown that HPV infection can be acquired by vertical transmission as well as via the placenta from mother to child 2-7 . Traditionally, HPV infection in the placenta has been considered to increase the risk of pregnancy complications 8-11 but HPV DNA has also been discovered from placentas from healthy pregnancies 3,5,12-14 and transabdominally obtained placental samples 7,15,16 . ...
... Cyanobacteria, Chloroplasts and Rhizobiales and sequences that could not be classified to domain level at OTU picking were removed from the results to control any possible bias. The presence and localization of HPV infection of our placental samples (Finnish Family HPV Study samples) have been examined before by Sarkola et al. 12 and Koskimaa et al. 7 and co-workers. Sarkola and coworkers confirmed the PCR positive HPV results by localizing the HPV16 and HPV6 DNA in syncytiotrophoblasts with tyramide amplified in-situ hybridization. ...
... The clinical study and its amendments were found acceptable by the HPV detection. HPV testing was performed with nested PCR using MY09/MY11 as external primers and GP05+/GP06+ as internal primers followed by genotyping with Multimetrix ® kit (Progen Biotechnik GmbH, Heidelberg, Germany), which detects 24 HPV types (low-risk HPV6, 11,42,43,44,and 70;18,26,31,33,35,39,45,51,52,53,56,58,59,66,68,73 and 82 types) as described in Koskimaa et al. 7 and Syrjänen et al. 62 . ...
We investigated the association between HPV infection and bacterial microbiota composition in the placenta, uterine cervix and mouth in thirty-nine women. HPV DNA genotyping of 24 types was conducted using Multimetrix®. Microbiota composition was characterized by 16S rRNA gene sequencing. HPV DNA was detected in 33% of placenta, 23% cervical and 33% oral samples. HPV16 was the most frequent type in all regions. HPV infection was associated with higher microbiota richness (p = 0.032) in the mouth but did not influence microbial diversity or richness in other samples. HPV infection was associated with higher abundance of Lactobacillaceae (p = 0.0036) and Ureaplasma (LDA score > 4.0, p < 0.05) in the placenta, Haemophilus (p = 0.00058) and Peptostreptococcus (p = 0.0069) genus in the cervix and Selenomonas spp. (p = 0.0032) in the mouth compared to HPV negative samples. These data suggest altered bacterial microbiota composition in HPV positive placenta, cervix and mouth. Whether the changes in bacterial microbiota predispose or result from HPV remains to be determined in future studies.
... Human papillomavirus (HPV) infection is generally regarded as a sexually transmitted disease. However, several studies, including those of our own [14,18,22,31], have shown that HPV can be detected in the oral mucosa of newborn babies and young, sexually inexperienced children, suggesting that alternative, non-sexual routes for HPV infection are plausible. ...
... We have shown a strong concordance between the HPV genotypes detected in the mother's genital tract and her offspring's oral samples [14], implying that the HPV-infected mother is the most probable source of HPV infection of the newborn. This view is also supported by others [8,10,16,20,24] reporting vertical transmission rates between 18.2 and 53.3% in the mother-baby pairs. ...
... This view is also supported by others [8,10,16,20,24] reporting vertical transmission rates between 18.2 and 53.3% in the mother-baby pairs. In line with this, we reported highly concordant serum antibody profiles for HPV-L1 antigens in the mother-baby pairs [14]. ...
The purpose of this study was to evaluate if an early exposure to human papillomavirus (HPV) during the prenatal period or infancy could result in HPV16-specific T helper (Th) responses resembling those of adults with HPV-induced lesions. We tested HPV16-specific cell-mediated immunity (CMI) in children born with HPV-positive umbilical cord blood and/or placenta or having persistent oral HPV infection and in constantly oral HPV-negative controls. Peripheral blood mononuclear cells from 33 children from the Finnish HPV Family Study cohort (mean age 14.7 years) were stimulated with peptide pools covering the amino acid sequence of the HPV16 E2, E6, and E7 proteins. Lymphocyte proliferation, secretion of cytokines (IFN-γ, TNF-α, IL-2, IL-4, IL-5, IL-10, IL-17A), and the frequency of Foxp3+ regulatory T-cells were determined in relation to the HPV DNA status during a 14-year follow-up. 73.6% of cases and 85.7% of controls responded against HPV16 E2, while reactivity against E6 was found in 10.5 and 35.7%, respectively. The proliferative response against E6 and E7 was more frequent in controls than in cases (p = 0.047). No HPV16-specific CMI response or antibodies were detected in two children with persistent oral HPV16. The profiles of induced cytokines indicated higher levels of IL-5, IL-10, and IL-17A in children with HPV DNA in placenta and/or cord blood than in other children. HPV16-specific CMI is common in HPV DNA-negative children. The cytokine profile in children infected with HPV16 during early life suggests that the viral dose and/or specific environment created by the placenta may have significant impact on the type of HPV-specific immunity.
... The participants were recalled for blood sampling, the mean age of the children being 12.2 years [19]. A detailed description of blood sample collection and processing has been published previously [19,[23][24][25][26]28]. PBMCs were stained in 96-well U-bottom plates in the concentration of 200,000-500,000 cells/well. ...
... In the present study, we analyzed the distribution of T cells and their subpopulations in the peripheral blood of mothers with either persistent oral or genital HPV16 infection using constantly HPV-negative mothers as the reference group. Similar analyses were also performed in the children of these mothers because immunological recognition of HPV16 seems to occur in early childhood [19,26,28,29]. ...
Only few studies exist on the phenotype distribution of peripheral blood lymphocytes concerning persistent oral HPV infection. T-lymphocyte subsets were phenotyped in women who had persistent genital or oral HPV16 infection, using HPV-negative women as a reference group. A subset of 42 mothers and their children (n = 28), were stratified into two groups according to the mothers’ HPV status. PBMCs from previously cryopreserved venous samples were immunophenotyped by flow cytometry. Proportions of the CD4+ or CD8+ lymphocytes by their immunophenotype subsets were compared between HPV-positive and -negative mothers and their children. The mean rank distribution of CD8+ memory cells was significantly higher among mothers with persistent genital HPV16 infection. The median levels of both the antigen-presenting CD4+ cells and activated CD8+ cells were significantly lower in mothers with persistent oral HPV16 infection. When oral and genital HPV16-persistors were analyzed as a group, a marker of terminal effector cells was significantly increased as compared to HPV-negative women. Significantly higher levels of activated CD4+, CD8+ and circulating CD8+ memory cells were found among children whose mothers had persistent oral HPV16 infection. Persistent HPV16 infections are associated with changes in peripheral blood T-lymphocyte subsets. The mother’s persistent oral HPV16 infection possibly results in immune alterations in her offspring.
... HPV infection can be acquired at an early age or even during birth, as suggested by the presence of HPV in the placenta, amniotic fluid, and cord blood (for review see [107][108][109]). Vertical transmission can be categorized as peri-conceptual [110], prenatal (during pregnancy) [69,111,112], and perinatal (during birth or immediately thereafter) [112][113][114][115]. ...
... HPV infection can be acquired at an early age or even during birth, as suggested by the presence of HPV in the placenta, amniotic fluid, and cord blood (for review see [107][108][109]). Vertical transmission can be categorized as peri-conceptual [110], prenatal (during pregnancy) [69,111,112], and perinatal (during birth or immediately thereafter) [112][113][114][115]. ...
Squamous cell papilloma (SCP) in the upper aero-digestive tract is a rare disease entity with bimodal age presentation both at childhood and in adults. It originates from stratified squamous and/or respiratory epithelium. Traditionally, SCPs have been linked to chemical or mechanical irritation but, since the 1980s, they have also been associated with human papillomavirus (HPV) infection. Approximately 30% of the head and neck SCPs are associated with HPV infection, with this association being highest for laryngeal papillomas (76–94%), followed by oral (27–48%), sinonasal (25–40%), and oropharyngeal papillomas (6–7%). There is, however, a wide variation in HPV prevalence, the highest being in esophageal SCPs (11–57%). HPV6 and HPV11 are the two main HPV genotypes present, but these are also high-risk HPVs as they are infrequently detected. Some 20% of the oral and oropharyngeal papillomas also contain cutaneous HPV genotypes. Despite their benign morphology, some SCPs tend to recur and even undergo malignant transformation. The highest malignant potential is associated with sinonasal inverted papillomas (7–11%). This review discusses the evidence regarding HPV etiology of benign SCPs in the upper aero-digestive tract and their HPV-related malignant transformation. In addition, studies on HPV exposure at an early age are discussed, as are the animal models shedding light on HPV transmission, viral latency, and its reactivation.
... 5,6,9 Además, en los recién nacidos positivos a la presencia del genoma del VPH, específicamente en SCU o placenta, se incrementa el riesgo de infección persistente del VPH en mucosa oral. 6,10,11 De acuerdo con las evidencias mencionadas, el VPH se ha detectado en SCU o en placenta; por lo tanto, el objetivo del presente estudio fue optimizar la muestra biológica de las unidades formadoras de colonicas (UFC) de los cultivos clonogénicos para extraer ADN y generar un biobanco de ADN que permita resolver ambigüedades de HLA o implementar el análisis de otros biomarcadores, así como detectar el genoma del VPH en las USCU del biobanco del Centro Nacional de la Transfusión Sanguínea. ...
... Entre los genotipos del VPH frecuentemente identificados en SCU se encuentran los VPH de alto riesgo que se asocian con alteración de la respuesta inmune, lesiones premalignas y cáncer. 5,6,9,10,11 Por lo tanto es pertinente analizar la presencia del VPH en una muestra de mayor tamaño de USCU. ...
Introducción:
Se requiere analizar diversos parámetros para el control de calidad adecuado de las unidades de sangre de cordón umbilical (USCU) cuando se utilizan con fines terapéuticos.
Objetivo:
Optimizar las unidades formadoras de colonias (UFC) de cultivos clonogénicos y detectar el genoma del virus del papiloma humano (VPH) en USCU.
Métodos:
Se incluyeron 141 muestras de sangre de cordón umbilical (SCU), de segmento y de UFC de cultivos clonogénicos de USCU. Se realizó extracción de ADN, cuantificación y amplificación por PCR del gen endógeno GAPDH. Se detectó el gen L1 del VPH con los oligonucleótidos MY09/MY11 y GP5/GP6+; los productos de PCR se migraron en electroforesis de agarosa. El ADN purificado de las UFC se analizó mediante electroforesis de agarosa y algunos ADN, con la técnica sequence specific priming.
Resultados:
La concentración de ADN extraído de UFC fue superior comparada con la de SCU (p = 0.0041) y la de segmento (p < 0.0001); así como la de SCU comparada con la de segmento (p < 0.0001). Todas las muestras fueron positivas para la amplificación de GAPDH y negativas para MY09/MY11 y GP5/GP6+.
Conclusiones:
Las USCU criopreservadas fueron VPH netativas; además, es factible obtener ADN en altas concentraciones y con alta pureza a partir de UFC de los cultivos clonogénicos.
... 5,6,9 In addition, in newborns who are positive for the presence of the HPV genome, specifically in UCB or the placenta, there is an increased risk for persistent HPV infection in oral mucosa. 6,10,11 According to the above-mentioned evidence, HPV has been detected in UCB or in the placenta; therefore, the purpose of the present study was to optimize the colony-forming units (CFUs) biological sample from clonogenic cultures to extract DNA and generate a DNA biobank that allows solving HLA ambiguities or implementing other biomarkers analysis, as well as detecting the HPV genome in UCBUs from the National Center of Blood Transfusion biobank. ...
... HPV genotypes that are frequently identified in UCB include high-risk HPVs that are associated with impaired immune response, premalignant lesions and cancer. 5,6,9,10,11 Therefore it would be pertinent to analyze the presence of HPV in a larger UCBU sample. ...
Introduction:
Analysis of several parameters is required for adequate quality control in umbilical cord blood units (UCBU) when used for therapeutic purposes.
Objective:
To optimize colony-forming units (CFU) from clonogenic cultures and to detect the human papillomavirus (HPV) genome in UCBU.
Methods:
One hundred and forty-one umbilical cord blood (UCB), segment or CFU samples from UCBU clonogenic cultures were included. DNA extraction, quantification and endogenous GAPDH gene PCR amplification were carried out. Subsequently, HPV L1 gene was detected using the MY09/MY11 and GP5/GP6+ oligonucleotides. PCR products were analyzed with electrophoresis in agarose gel. CFU-extracted purified DNA was analyzed by electrophoresis in agarose gel, as well as some DNAs, using the sequence-specific priming technique.
Results:
CFU-extracted DNA concentration was higher in comparison with that of UCB (p = 0.0041) and that of the segment (p < 0.0001), as well as that of UCB in comparison with that of the segment (p < 0.0001). All samples were positive for GAPDH amplification and negative for MY09/MY/11 and GP5/GP6+.
Conclusions:
Cryopreserved UCBUs were HPV-negative. Obtaining CFU DNA from clonogenic cultures with high concentrations and purity is feasible.
... The other study in Brazil has shown that the prevalence of human parvovirus B19 on UCB and placenta by nested PCR method was 3/138 (~2.2%) (37). Based on Finnish experiences, they provided 3.5% human Parvovirus B19 DNA in 311 umbilical cord blood samples, which was detected by the PCR method (38). On the other hand, two studies in Korea and Austria, respectively, used DNA-Chip and PCR methods reported no existence of parvovirus DNA in UCB samples (39,40). ...
Background and Objectives: Umbilical cord blood (UCB) was used to source hematopoietic stem cells in the past. Despite the apparent advantages of UCB transplantation, virus reactivation poses a considerable danger in allogeneic hematopoietic stem cell transplantation (HSCT). Human Parvovirus B19 is regarded as a potential threat to UCB contamination. This study aimed to evaluate the prevalence of parvovirus B19 in cord blood donors by Semi-Nested PCR. This study is the first large-scale report of the B19 DNA in cord blood donors in Iran.
Materials and Methods: A total of 691 umbilical cord blood were collected under standard procedure. Then, DNA from buffy coat and plasma were extracted, and semi-nested PCR was performed for all samples.
Results: Two out of 691 samples (0.29%) indicated viremia in plasma and buffy coat.
Conclusion: In this line, designing and validating a quantitative PCR assay for detection, quantification, and discrimination of Human B19 DNA genotypes of cord blood donors is necessary to enhance the safety of this source of stem cells.
... respectively [61]. While most studies on pregnant women have searched for infection in the uterine cervix [60,61], HPV DNA has also been detected in the placenta [62][63][64][65], amniotic fluid [66,67], and umbilical cord [34], its presence in these tissues implying vertical transmission to the infant [68]. As plenty of requirements are needed in order to accommodate the products of conception, pregnancy is characterized by a myriad of adaptive changes, ranging from anatomical, cardiovascular, and metabolic, to hormonal and immunological [69]. ...
The human papilloma virus (HPV) infection, caused by a ubiquitous virus typically transmitted through the direct contact of infected organs, either through the skin or mucosa, is the most common sexually transmitted infection, placing young women at a high risk of contracting it. Although the vast majority of cases spontaneously clear within 1–2 years, persistent HPV infection remains a serious concern, as it has repeatedly been linked to the development of multiple malignancies, including cervical, anogenital, and oropharyngeal cancers. Additionally, more recent data suggest a harmful effect of HPV infection on pregnancy. As the maternal hormonal environment and immune system undergo significant changes during pregnancy, the persistence of HPV is arguably favored. Various studies have reported an increased risk of adverse pregnancy outcomes among HPV-positive women, with the clinical impact encompassing a range of conditions, including preterm birth, miscarriage, pregnancy-induced hypertensive disorders (PIHD), intrauterine growth restriction (IUGR), low birth weight, the premature rupture of membranes (PROM), and fetal death. Therefore, understanding the mechanisms employed by HPV that negatively impact pregnancy and assessing potential approaches to counteract them would be of interest in the quest to optimize pregnancy outcomes and improve child survival and health.
... The human papillomavirus (HPV), was detected in the cervix in 15-25% of pregnant women [27,28] and a cervical HPV infection during pregnancy was associated with an increased incidence of miscarriages [29], premature membrane rupture [30], spontaneous preterm birth, pre-eclampsia [31], and placental "villitis" not otherwise specified, however, HPV DNA was also discovered in the placenta of healthy pregnancies [32] and placenta samples obtained trans-abdominally. The relationship between HPV infection and pregnancy outcomes is unclear. ...
Background
It is believed that HPV infection can result in the death of placental trophoblasts and cause miscarriages or preterm birth. In clinical cases of placental villi positive for HPV DNA reported by other authors, contamination is suspected in the act of crossing the cervical canal. We analyzed placental samples of women who resorted to elective abortion obtained by hysterosuction of ovular material, bypassing any contact with the cervical canal and vagina.
Methods
We studied the chorionic villi of the placenta of 64 women who resorted to voluntary termination of pregnancy, in the first trimester. To avoid contamination of the villi by the cervical canal, we analyzed placental samples obtained by hysterosuction of ovular material, bypassing any contact with the cervical canal and vagina. All samples of chorionic villi were manually selected from the aborted material and subjected to research for HPV DNA.
Results
HPV DNA was detected in 10 out of 60 women (16.6%). The HPV DNA identified in the placenta belonged to genotypes 6, 16, 35, 53, and 90.
Conclusion
The study shows that papillomavirus DNA can infect the placenta and that placenta HPV infection can occur as early as the first trimester of pregnancy.
... A viral origin has been suggested for this type of congenital tumors ,but has not been proven [12] and these lesion are widely regarded to be more likely haematomatous rather than infection [12] The microscopic patterns of the oral cavity suggested diagnoses of oral papilloma and epidermal hyperplasia respectively.The infection with BPV seems most likely to have been vertically transmitted .The concordance between BPV genotypes detected in the blood of the dams and the oral cavity, the pathological sample of their offspring support a vertical hematogenoues transmission pathway ,rather than ascending ewe infection or an infection at the time of birth. Therefor ovine placenta plays an important role in the transmission of BPVS Vertical transmission of PVs is well recognized and it has been found that the presence of HPV in placenta or in the cord blood increased the risk of the newborn to carry HPV in the oral cavity mucosa [13,14]. ...
This study was undertaken to investigate the prevalence of papilloma virus and granulomatous reaction which occur naturally in sheep in Mosul area, Iraq. These lesion were diagnosed in 10 cases out of a total 325(3%) examined cases, papilloma percentage was 1.23% and granulomatous infection percentage was 1.84% .The gross and microscopic features of papilloma showed a red tissue nodule hanging from the inner surface (mucosa) of the lower lip .Microscopically, the mass was formed from multiple papillary protrusions of fibrous connective tissue with marked increase in the number and size of inflammatory cell. The macro and micro examination of granulomatous reaction showed a subcutaneous and neoplastic mass of tissue which were connected to the jaw bone at the level of seventh and eighth cheek teeth and upon opening the skin .A white mass was observed while the microscopic exam showed the presence of a severe fibrous reaction in the form of inflammation and neoplasm granuloma. Finally, this research determined the type of papilloma and granulomatous reaction in local sheep and their prevalence rates, with accurate description of gross and microscopic lesions.
... A viral origin has been suggested for this type of congenital tumors ,but has not been proven [12] and these lesion are widely regarded to be more likely haematomatous rather than infection [12] The microscopic patterns of the oral cavity suggested diagnoses of oral papilloma and epidermal hyperplasia respectively.The infection with BPV seems most likely to have been vertically transmitted .The concordance between BPV genotypes detected in the blood of the dams and the oral cavity, the pathological sample of their offspring support a vertical hematogenoues transmission pathway ,rather than ascending ewe infection or an infection at the time of birth. Therefor ovine placenta plays an important role in the transmission of BPVS Vertical transmission of PVs is well recognized and it has been found that the presence of HPV in placenta or in the cord blood increased the risk of the newborn to carry HPV in the oral cavity mucosa [13,14]. ...
This study was undertaken to investigate the prevalence of papilloma virus and granulomatous reaction which occur naturally in sheep in Mosul area, Iraq. These lesion were diagnosed in 10 cases out of a total 325(3%) examined cases, papilloma percentage was 1.23% and granulomatous infection percentage was 1.84% .The gross and microscopic features of papilloma showed a red tissue nodule hanging from the inner surface (mucosa) of the lower lip .Microscopically, the mass was formed from multiple papillary protrusions of fibrous connective tissue with marked increase in the number and size of inflammatory cell . The macro and micro examination of granulomatous reaction showed a subcutaneous and neoplastic mass of tissue which were connected to the jaw bone at the level of seventh and eighth cheek teeth and upon opening the skin .A white mass was observed while the microscopic exam showed the presence of a severe fibrous reaction in the form of inflammation and neoplasm granuloma. Finally, this research determined the type of papilloma and granulomatous reaction in local sheep and their prevalence rates, with accurate description of gross and microscopic lesions.
... Oral cavity is the first possible route of HPV infection, especially in children, and could even be the first anatomic site of productive infection resulting in HPV-specific immunity (Koskimaa et al., 2012;Koskimaa et al., 2014). Our main interest was to find out whether any CMI-specific indicators could predict the outcome of oral HPV16 ...
Objectives
Natural history of human papillomavirus (HPV) infection in the head and neck region is poorly understood, and their impact on collective HPV‐specific immunity is not known.
Materials and methods
In this study, we have performed a systematic analysis of HPV16‐specific cell‐mediated immunity (CMI) in 21 women with known oral and genital HPV DNA status and HPV serology (Ab) based on 6‐year follow‐up data. These women being a subgroup from the Finnish Family HPV Study were recalled for blood sampling to be tested for their CMI‐responses to HPV16 E2, E6, and E7 peptides.
Results
The results showed that HPV16 E2‐specific lymphocyte proliferation was more prevalent in women who tested HPV16 DNA negative in oral mucosa and were either HPV16 seropositive or negative than in HPV16 DNA+/Ab+ women (p = 0.046 and p = 0.035). In addition, the HPV16 DNA−/Ab− women most often displayed E6‐specific proliferation (p = 0.020). Proportional cytokine profiles indicated that oral HPV16‐negative women were characterized by prominent IFN‐γ and IL‐5 secretion not found in women with persisting oral HPV16 (p = 0.014 and p = 0.040, respectively).
Conclusions
Our results indicate that the naturally arising immune response induced by oral HPV infections displays a mixed Th1/Th2/Th17 cytokine profile while women with persisting oral HPV16 might have an impaired HPV16‐specific CMI, shifted partly toward a Th2 profile, similarly as seen earlier among patients with high‐grade genital HPV lesions. Thus, the lack of HPV 16 E2 and E6 specific T memory cells and Th2 cytokines might also predispose women for persistent oral HPV16 infection which might be related to the risk of cancer.
... О вертикальной передаче ВПЧ Заражение ВПЧ традиционно рассматривается как инфекция, передаваемая половым путем (горизонтально): при генитально-генитальных, генитально-оральных, генитально-мануальных и других контактах с зараженным эпителием. Однако несколько авторов сообщили о присутствии ВПЧ в эпителии ротовой полости, слизистой оболочке глаза, а также на гениталиях новорожденных и детей младшего возраста, не имевших сексуальных контактов [10][11][12][13]. Оказалось, что кроме полового возможны и иные пути заражения, например интранатальный -при прохождении плода по родовым путям ВПЧ-зараженной матери, из плаценты или через пуповинную кровь, где также встречаются ВПЧ [13,14]. ...
Cervical cancer (CC) incidence rate made up about 5 % in overall women cancer incidence in Russia in 2015. CC morbidity rose by 24.47 %during 2005–2015. Despite the fact that aggregated standardized cancer mortality rates for both men and women during 2005–2015 declined, women CC mortality increased by 8.3 %. CC is the leading cancer mortality cause in women aged 30–39 years. Moreover growth of oraland pharynx cancer incidence rates in both genders as well as penile cancer in men all indicate to an unfavorable trend. The present Reviewpart contains data on HPV-associated cancers in Russia, vertical HPV transition as well as preventive HPV vaccines.
... Thus HPV susceptibility may be assisted by weak immune resistance shared by family members. HPV infections are usually sexually transmitted which would be unlikely to explain familial risk, and non-sexual transmissions from an infected mother during pregnancy or early childhood are supposed to be rare 19,20 . We assume that shared life-style with many sexual partners may the explanation to the observed familial risks. ...
Literature on familial risk of carcinomas in situ (CISs) is limited because many cancer registries do not collect information on CIS. In Sweden CISs are collected, and we used these data to analyze familial relative risks (RRs) for concordant (CIS-CIS) types of anogenital (cervical, other female and male genital and anal) and skin squamous cell CIS; additionally RRs were assessed between CIS types and between CIS and invasive forms. RRs were calculated for the offspring generations when family members were diagnosed CIS. Case numbers for CIS ranged from 330 in anal to 177,285 in cervical CIS. Significant concordant CIS-CIS RRs were 2.74 for female genital, 1.77 for cervical and 2.29 for SCC skin CISs. The CIS forms associated also with each other, except for cervical and skin CIS types. RRs for concordant CIS-invasive cancer associations were lower than CIS-CIS associations. Cervical CIS associated with non-Hodgkin CIS which may suggest immune dysfunction as a contributing factors. The results for anogenital CIS types suggest that life style related human papilloma virus infections contributed to the observed familial associations. Lower risks for CIS-invasive cancer than CIS-CIS suggest that CIS and invasive cancers share only partially risk factors that underlie familial clustering.
... The association of HPV with head and neck cancers is well-established. [6] Vertical transmission of HPV infections from an infected mother to her infant during childbirth has been reported [7], however, this would be highly speculative in our case. ...
... HPV seropositivity is found already in children and teenagers, implicating that non-sexual transmission early in life may be a significant way of acquiring the infection [30,31]. Vertical transmission from mother to neonate during and after pregnancy has been reported [32][33][34] already in the placenta [35][36][37]. Children of HPV-positive mothers had a 33% higher risk of becoming infected than children of HPV-negative mothers. ...
Sexual intercourse is regarded as the primary route of human papillomavirus (HPV) transmission. Reported rates of the genotype-specific genital concordance of HPV infection among heterosexual partners vary. Most studies have evaluated only male/female genital transmission, but lately, the oral region has gained interest because of a rising trend of HPV-associated oropharyngeal cancer. Risk factors for type-specific concordance have been reported as an increasing number of younger couples, persistent HPV infection, higher frequency of sexual intercourse, rising number of spouse's lifetime sexual partners, and sexual relations with prostitutes. However, the concordance of the same genital HPV genotype does not absolutely mean that it has been transmitted by the current partner. There are also other possible non-sexual transmission routes. The detected HPV infection may also be a reactivation of a previous infection. The high complexity of HPV transmission dynamics within an individual him-/herself as well as within sexual couples is discussed in this article.
... Finská studie sledovala novorozence matek s převážně vaginálním porodem a ukázala, že s odstupem několika měsíců od narození dochází ke snížení prevalence orálních HPV infekcí (prevalence HPV při narození: 22,5 %; 1. měsíc od narození: 18,7 %; 2. měsíce od narození: 16,9 %). Tato orální HPV infekce tedy představuje spíše osídlení dutiny ústní než infekci v pravém slova smyslu [11]. ...
BACKGROUND: Human papillomaviruses (HPV), a group of small, tumorigenic DNA viruses, are causally linked to cervical cancer and various other anogenital, oral, and oropharyngeal malignancies in both males and females. The purpose of this systematic review is to summarize the most recent data on the prevalence of oral HPV in healthy populations in Europe. METHODS: A systematic review of the European studies on the prevalence of oral HPV infections published from January 2011 to September 2017. RESULTS: The overall prevalence rates of oral HPV in healthy populations vary between 1.2% and 11.6%, with high-risk types of HPV (HR HPV) detected in 2.2% to 7.2% of individuals and HPV16 in 0.2% to 2.9% of individuals. The overall prevalence rate of oral HPV infections was considerably higher in men having sex with men as compared to heterosexual men and women. CONCLUSION: The prevalence rates of oral HPV infection in European populations are comparable to the results of the studies conducted in the USA and Asia. However, the European studies did not focus on the risk factors for oral HPV infection in healthy populations. A statistically significant relationship between oral sex, smoking, and HPV infection as observed in extensive studies from the USA was confirmed by a single European study.
... Therefore, ovine placenta may play an important role in the transmission of BPVs, just several other viruses do in sheep. Vertical transmission of HPVs is well recognized and it has been found that the presence of HPV in placenta and/or in cord blood increased the risk of the newborn to carry HPV DNA in the oral mucosa 24,33,34 . To the authors' knowledge, vertical transmission of a BPV in a sheep has never been previously reported. ...
Congenital fibropapillomatosis of the gingiva and oral mucosa and epidermal hyperplasia of the lip are described, for the first time, in two newborn lambs. Expression of the E5 oncoprotein of bovine deltapapillomavirus types 2 (BPV-2) and -13 (BPV-13) was detected in both fibropapillomas and the hyperplastic epidermal cells suggesting the BPV infection was the cause of the proliferative lesions. No DNA sequences of BPV-1 and BPV-14 were detected. Both BPV-2 and BPV-13 DNA were also amplified from peripheral blood mononuclear cells (PBMCs) of the newborn lambs' dams. The concordance between BPV genotypes detected in the blood of dam and the oral and skin pathological samples of their offspring suggests that a vertical hematogeneous transmission was most likely source of BPV infection. Immunoblotting revealed the presence of E5 dimers allowing the viral protein to be biologically active. E5 dimers bind and activate the platelet derived growth factor β receptor (PDGFβR), a major molecular mechanism contributing to disease. The detection of E5 protein within the proliferating cells therefore adds further evidence that the BPV infection was the cause of the proliferative lesions seen in these lambs. This is the first evidence of vertical transmission of BPVs in sheep resulting in a clinical disease.
... This null allele was found in one mother-child pair and two other mothers in our Finnish cohort (4/634). [4][5][6] ...
... A study conducted by Koskimaa et al in children whose mothers had cervical intra-epithelial neoplasm lesions, demonstrated that these children had HPV type 16-specific cell-mediated immunity. HPV infections persistent earlier in life can affect the outcome of subsequent genital or oral HPV infections (82). ...
Human papilloma viruses (HPV) are a small group of non‑enveloped viruses belonging to the Papillomaviridae family with strong similarities to polyoma viruses. The viral particles consist of a genome in the form of a circular double‑stranded DNA, encompassing eight open reading frames, as well as a non‑enveloped icosahedral capsid. HPV infection is considered the most common sexually transmitted disease in both sexes and is strongly implicated in the pathogenesis of different types of cancer. 'High‑risk' mucosal HPV types, predominantly types 16, 18, 31, 33 and 35, are associated with most cervical, penile, vulvar, vaginal, anal, oropharyngeal cancers and pre‑cancers. Screening for HPV is necessary for the prognosis and for determining treatment strategies for cancer. Novel HPV markers, including proteomic and genomic markers, as well as anti‑papillomavirus vaccines are currently available. The aim of this comprehensive review was to thoroughly present the updated information on virus development, cancer occurrence, treatment and prevention strategies, in an attempt to shed further light into the field, including novel research avenues.
... 38 Occasionally, HPV can be transmitted to the oral mucosa by modes other than sexual activity, such as vertical transmission from mother to son. 39 The majority of HPV infections are transient and undetectable by sensitive methods, such as polymerase chain reaction (PCR), within a period of 1-2 years. 40 The prevalence tends to peak after the first sexual intercourse encounter and remains high with each new sex partner. ...
The increasing prevalence of human papilloma virus (HPV)-positive oral tumors can be considered an epidemic. Although the incidence of HPV cervical cancer is decreasing, the incidence of oral cavity and oropharyngeal cancers associated with HPV is increasing. The presence of certain HPV genotypes could be a predictor of future oral cancer lesions, although lesions associated with HPV could be less aggressive and exhibit a higher survival rate. In the present study, we review the most important biologic, clinic, epidemiologic, and prognostic factors associated with HPV infection and oral cancer.
... Secondary infections have been reported in HPV patients [44,45]. It is still unclear how long it takes for a subclinical infection to manifest as visible disease and what factors trigger the process. ...
We report secondary cutaneous infections in the mouse papillomavirus (MmuPV1)/mouse model. Our previous study demonstrated that cutaneous MmuPV1 infection could spread to mucosal sites. Recently, we observed that mucosal infections could also spread to various cutaneous sites including the back, tail, muzzle and mammary tissues. The secondary site lesions were positive for viral DNA, viral capsid protein and viral particles as determined by in situ hybridization, immunohistochemistry and transmission electron microscopy analyses, respectively. We also demonstrated differential viral production and tumour growth at different secondarily infected skin sites. For example, fewer viral particles were detected in the least susceptible back tissues when compared with those in the infected muzzle and tail, although similar amounts of viral DNA were detected. Follow-up studies demonstrated that significantly lower amounts of viral DNA were packaged in the back lesions. Lavages harvested from the oral cavity and lower genital tracts were equally infectious at both cutaneous and mucosal sites, supporting the broad tissue tropism of this papillomavirus. Importantly, two secondary skin lesions on the forearms of two mice displayed a malignant phenotype at about 9.5 months post-primary infection. Therefore, MmuPV1 induces not only dysplasia at mucosal sites such as the vagina, anus and oral cavity but also skin carcinoma at cutaneous sites. These findings demonstrate that MmuPV1 mucosal infection can be spread to cutaneous sites and suggest that the model could serve a useful role in the study of the viral life cycle and pathogenesis of papillomavirus.
... In this study, oral hrHPV infection was independently associated with age (30-34 and 60-64 years), male sex, increasing number of lifetime sexual partners, and current number of cigarettes smoked per day in multivariate models (Gillison et al., 2012). It is also unclear whether infection may occur with open-mouth kissing (D'Souza et al., 2009) or vertical transmission (Koskimaa et al., 2012). Fortunately, the majority of hrHPV infections will clear within 12 months (Kreimer et al., 2013), and only about 11,000 of the over 300 million Americans will develop HPV-related OPSCC each year (CDC, 2014a). ...
The objective of the study is to determine the prevalence of high-risk human papillomavirus (hrHPV) infection in tonsillar swabs and tissue: Patients undergoing tonsillectomy for nonmalignant causes were enrolled. A flocked swab and fresh tissue were collected from the left and right tonsil of each patient. Specimens were tested for hrHPV DNA using the Roche cobas test and for the presence of E6/E7 messenger RNA using the Hologic Aptima hrHPV test. Of the 193 patients enrolled, 129 were in the pediatric group (ages 1-12 years; median, 5 years), and 64 were in the adult group (ages 13-55; median, 22 years). All swab and tissue specimens were negative for hrHPV by both methods. Positive, negative, and internal controls performed as expected. We found a 0% rate of infection indicating that detectable hrHPV infection in tonsillar tissue appears to be uncommon in the children and adults in the population sampled.
... Confirmation of the perinatal transmission in different mucosa (genital, oral) was subsequently supported in several studies, although the exact mode of transmission is not well understood. Previous small studies have reported widely varying rates of infection in newborns, with estimates ranging from 4 to 79% among day old infants born to mothers testing positive for HPV during pregnancy [12][13][14][15][16][17][18][19][20][21][22][23][24]. ...
Perinatal route of transmission of human papillomavirus (HPV) has been demonstrated in several small studies. We designed a large prospective cohort study (HERITAGE) to better understand perinatal HPV. The objective of this article is to present the study design and preliminary data. In the first phase of the study, we recruited 167 women in Montreal, Canada, during the first trimester of pregnancy. An additional 850 are currently being recruited in the ongoing phase. Cervicovaginal samples were obtained from mothers in the first trimester and tested for HPV DNA from 36 mucosal genotypes (and repeated in the third trimester for HPV-positive mothers). Placental samples were also taken for HPV DNA testing. Conjunctival, oral, pharyngeal and genital samples were collected for HPV DNA testing in children of HPV-positive mothers at every 3-6 months from birth until 2 years of age. Blood samples were collected in mother and children for HPV serology testing. We found a high prevalence of HPV in pregnant women(45%[95%CI:37-53%]) and in placentas(14%[8-21%]). The proportion of HPV positivity (any site) among children at birth/3-months was 11%[5-22%]. HPV was detected in children in multiple sites including the conjunctiva(5%[10-14%]). The ongoing HERITAGE cohort will help provide a better understanding of perinatal HPV.
During recent years, evidence of human papillomavirus (HPV) infection emerged as a major prognostic biomarker in head and neck squamous cell carcinomas (HNSCCs), especially those arising from the oropharynx. HPV-associated oropharyngeal carcinomas (OSCCs) represent a clinically distinct form of HNSCC with a different clinical profile, prognosis, and therapeutic options than HPV-non-related HNSCC. Most importantly, the accurate diagnosis of HPV causality in OSCCs is likely to influence therapeutic decisions in affected patients in the near future. Indeed, the clinical significance of detecting HPV in HNSCC has resulted in a growing expectation for HPV testing of HNSCCs. Many different HPV tests exist and much more information about their specific technical, analytical, and clinical properties are available. The objective of this chapter is to address the current state of HPV detection, explain various techniques of HPV detection and analyze the strengths and weaknesses of some of the more commonly used assays. As no single test has been universally accepted as a best method, the challenge for the oncologic community is to implement standardized HPV testing using a method that is highly accurate, technically feasible, cost effective, and readily transferrable to the diagnostic pathology laboratory. Furthermore, in this chapter we will discuss the role of HPV in OSCC and the clinical impact of HPV status as a biomarker for HNSCC.KeywordsHPVOropharyngeal cancerDetection methodsPCRp16 immunostainingISHE6E7
Human papillomavirus (HPV), the most prevalent sexually transmitted disease worldwide , is the causative agent for several genital and oropharyngeal cancers and a suspected agent for many malignancies. HPV is associated with several adverse health outcomes during pregnancy. Infants are also at risk of HPV infection via different transmission routes: vertically from an infected mother and horizontally through sexual or non-sexual contact with infected individuals. Several HPV manifestations have been identified during childhood, ranging from common skin infections to severe complications such as juvenile recurrent respiratory papillomatosis. This review aims to provide a comprehensive overview of the epidemiology, manifestations, and treatment strategies of HPV infection during pregnancy and childhood. Moreover, we underline the role of vaccination in preventing complications.
Introduction
Although infection by human papillomavirus (HPV) is mainly considered a sexually transmitted disease, newborns exposed to the virus in the perinatal period can also be infected through mechanisms that are not yet fully understood. The aim of our study was to increase our understanding of neonatal oropharyngeal infection by HPV, trying to establish its frequency, mechanisms of infection and persistence through age 2 years.
Material and methods
We conducted a prospective, observational and descriptive study in a cohort of neonates born vaginally whose mothers carried HPV in the lower genital tract at the time of delivery. Tests for detection of HPV in amniotic fluid, venous cord blood and oropharyngeal secretions were performed in every neonate, and we conducted microbiological follow-up of infants colonized by HPV up to age 2 years.
Results
The prevalence of oropharyngeal colonization at birth was 58.24%. In the 24-month follow-up, the proportions of clearance and persistence of HPV in the oropharynx were 94.34% and 5.66%, respectively.
Conclusions
The results of this case series suggest that neonatal oropharyngeal colonization by HPV, while frequent in the postpartum period, is usually a self-limited process, and the main mechanism of infection transvaginal intrapartum vertical transmission. Although colonization in most neonates is transient and asymptomatic, the clinical significance of persistent carriage remains unknown.
Resumen
Introducción
Aunque la infección por el virus del papiloma humano (VPH) es considerada esencialmente como una enfermedad de transmisión sexual, los recién nacidos expuestos al virus durante el período perinatal pueden también contraer la infección por mecanismos que aún no se conocen con exactitud. Con la presente investigación pretendemos profundizar en el estudio de la infección orofaríngea neonatal por VPH, tratando de establecer su frecuencia, los mecanismos preponderantes de contagio y la persistencia en los dos primeros años de vida.
Material y métodos
Estudio observacional, descriptivo y prospectivo de una cohorte de recién nacidos por parto vaginal cuyas madres eran portadoras de VPH en el tracto genital inferior en el momento del parto. Se determinó la presencia del virus en líquido amniótico, sangre venosa de cordón y orofaringe neonatal en todos los casos, manteniendo un seguimiento microbiológico de los neonatos colonizados por VPH hasta los dos años de vida.
Resultados
La tasa de colonización orofaríngea por VPH al nacimiento fue del 58,24%. Para el seguimiento realizado de 24 meses las proporciones de aclaramiento y de persistencia viral en la orofaringe neonatal fueron del 94,34 y del 5,66%, respectivamente.
Conclusiones
Los resultados de nuestra serie hacen suponer que, aunque frecuente en el posparto, la colonización orofaríngea neonatal es un proceso generalmente autolimitado, cuyo principal mecanismo infectivo es la transmisión vertical transvaginal e intraparto. Aunque la mayoría de estas colonizaciones son transitorias y asintomáticas, la trascendencia clínica de los casos de persistencia viral sigue siendo un enigma.
The majority of sexually active individuals becomes infected with human papillomavirus (HPV) at least once in their lifetime. Pathways for HPV transmission vary across different mucosal sites per individual. They include autoinoculation within one host, direct transmission between individuals (including perinatal transmission and transmission during sexual activity), and indirect transmission through contact with hands. The authors aim to clarify the prevalence and route of transmission per anatomic site, inter‐ and intra‐individually, using a narrative review of the literature. In conclusion, transmission of HPV to the oral cavity and oropharynx is hypothesised to occur mainly through sexual contact. Transmission of particles through saliva has not been proven and daily living activities are not a documented source of HPV infection. Oropharyngeal HPV related cancer survivors and their partners do not show increased risk of infection during sexual intercourse. Transmission of HPV to the oral cavity (autoinoculation with fingers or transmission through saliva in deep kissing) is probably of limited importance.
To assess the dynamics of human papillomavirus (HPV) serology, we analyzed HPV6-,11-,16-,18-, and 45 antibodies in infants during the first 36 months of their life. Serial serum samples of 276/327 mother–child pairs were collected at baseline (mothers) and at months 1, 2, 6, 12, 24 and 36 (offspring), and tested for HPVL1-antibodies using the GST-L1 assay. Concordance between maternal and infant HPV-antibody levels remained high until month-6 (p < = 0.001), indicating maternal antibody transfer. At 1 month, 40–62% of the infants tested seropositive to any of the 5 HPV-types. Between 1–3 years of age, 53% (58/109) of the children born to HPV-seronegative mothers tested HPV-seropositive. Times to positive seroconversion varied between13.4 and 18.7 months, and times to negative seroconversion (decay) between 8.5 and 9.9 months. Significant independent predictors of infants’ seroconversion to LR-HPV were hand warts and mother’s history of oral warts and seroconversion to LR-HPV. No predictors of seroconversion to HR-HPV were identified. Maternal HPV-IgG-antibodies are transferred to her offspring and remain detectable for 6 months, corroborating the IgG molecule’s half-life. Seroconversion to HPV-genotypes 6, 11, 16 and 18 was confirmed among children born to HPV-seronegative mothers, implicating an immune response to these HPV-genotypes during early infancy.
Introduction:
Human papillomavirus (HPV) represents a group of DNA viruses, sexually transmitted, and widely accepted as a cause of invasive squamous cell carcinomas. The virus prevalence is critical worldwide. However, the possibility of perinatal transmission during pregnancy is not well understood as well as the risks for the newborn.
Methods:
Our study analyzed pregnant women referred to the obstetric outpatient room of the Department of Gynecology and Obstetrics of Sant'Anna and San Sebastiano's University Hospital in Caserta, Italy. Cervicovaginal samples were achieved from patients during the first trimester and tested for HPV. The specimen was repeated during the third trimester for HPV-positive patients. After the birth, we took a placenta sample and an eye, pharyngeal, mouth, and genital samples in children from HPV positive mothers, at 36-48 hours after birth and three and six months.
Results:
We found out a high prevalence of HPV infections in the recruited patients: 71 participants were positive at the HPV test in the first trimester (45%), and 17 (14 %) showed a positivity in the placental samples. However, there was a low prevalence of viral infection in newborns, and six newborns were positive for HPV at birth (9%).
Conclusions:
HPV vertical transmission represents a critical obstetric topic, and the transplacental passage of the virus represents a possible cause. However, further studies are necessary to deepen the pathological mechanism and assess the risks for the newborn.
Objectives:
i) To compare the placental human papilloma virus (HPV) deoxynucleic acid (DNA) status of preterm deliveries with full term deliveries and to identify high risk (HR) genotypes (HPV 16 and 18); and ii) To compare the perinatal outcomes of HPV positive with HPV negative pregnant women.
Methods:
A case control study was carried out on 100 antenatal women with singleton live pregnancies admitted in labor ward of a tertiary care teaching hospital from April 2017 to March 2018. The two study groups were i) spontaneous preterm deliveries between 24 and 36 + 6 weeks (n=50) and ii) full term deliveries ≥37 weeks (n=50). The placental tissue was analysed for HPV DNA and HR HPV genotypes were detected by type specific primers. A comparative analysis of perinatal outcomes between HPV positive and negative women was done.
Results:
An overall placental tissue HPV prevalence of 12% (12/100) was observed in study cohort which was not significantly different between preterm and full term deliveries (16 vs. 8%, p=0.218). HPV 16 was significantly associated with preterm births (p=0.04). Both HPV affected and non-affected women were comparable in terms of mode of delivery and neonatal outcomes. However, a statistically significant association of preterm neonatal intensive care admissions with HR HPV 16 genotype was observed (p=0.04).
Conclusions:
Spontaneous preterm births can be attributed to placental HPV infection, specifically HR HPV 16 genotype. This association identifies a potentially preventable cause of prematurity and its associated complications, in wake of availability of an effective vaccine.
Children may present to their pediatrician, dermatologist, urologist, or gynecologist with anogenital skin disease. This portion of the chapter highlights some of the most commonly encountered conditions affecting infants, prepubertal children, and adolescents, including nonspecific vulvovaginitis, perineal pyramidal protrusion, labial adhesion, diaper dermatitis, infantile hemangioma, lichen sclerosus and balanitis xerotica obliterans, vitiligo, cutaneous Crohn disease, molluscum contagiosum, herpes simplex virus, human papillomavirus, pinworms, and non-sexually acquired genital ulceration.
Viral pandemics have shown that infected pregnant women are at risk of adverse pregnancy outcomes. Current evidence suggests that a pregnant woman’s immune system undergoes a transformation necessary to maintain pregnancy and fetal growth. The prevalence of human papillomavirus (PVI) is high, and its role in adverse pregnancy outcomes and reproductive loss is highly controversial. About 90% of cases of persistent human papillomavirus infection (PVI) are eliminated within one to two years. The role of the immune system in the elimination and persistence of PVI has been proven; however, there is no clear understanding of the mechanisms whereby PVI infected cells escape immune surveillance up to the present day. In addition, the immune mechanisms underlying the PVI persistence constitute a pathogenetic basis for the development of mechanisms of infertility, miscarriage and pregnancy pathology. Genetic polymorphism of the mother and the developing fetus, persistent PVI types and microbial landscape are modulating factors with an unexplained contribution in the transformation of quantity of introduced influences into the qualitative change in the biological state. The foreign and Russian research results analysed by the authors show that timely and adequate therapy of PVI may contribute to the preservation of reproductive potential and prevention of obstetric losses. The modern approach to the treatment of persistent PVI suggests the use of antiviral and immunomodulatory therapy. Due to its immunomodulatory and antiviral properties, inosine pranobex is used to treat viral diseases such as PVI, herpes simplex viruses, cytomegalovirus, Epstein-Barr virus and influenza.
There has been a considerable increase in the number of caesarean sections (C-sections) in the last 30 years. Between 2009 and 2017, Romania has reported an increase with 32.1% of the number of C-sections. The consensus regarding the obstetrical indications of the caesarean section has changed. This is mainly due to improvement in appreciating more specific fetal death risks or fetal hypoxemia, and to allow pregnancy for severe medical conditions (kidney transplant, valvular cardiac prostheses etc.). The caesarean section rate is also increased by the number of C-sections at the patient’s request. Some patients request a caesarean delivery without a valid medical indication because they are afraid of episiotomy, of prolonged and painful labor, vaginal trauma or urinary incontinence associated with a vaginal birth or because of some false medical beliefs. Our article focuses on evidence-based medicine on false beliefs about the indications of the C-section in Romania, the intriguing tale of how pregnant women request a C-section, sometimes encouraged by healthcare givers. The analyzed indications which are misbelieved are: fetal nuchal cord, oligohydramnios at term for normally structured fetuses, maternal obesity, fetal macrosomia, the 40-week pregnancy, hepatitis B and C, human papillomavirus (HPV) infection, and uncomplicated myopia.
b> Background: The association of human papillomavirus (HPV) with head and neck squamous cell carcinoma (HNSCC) was first described in 1982–1983 by the authors of this review. Prompted by this discovery 35 years ago, an entirely new field of HPV research has emerged, resulting in a paradigm shift from smoking and alcohol as the only etiological factors to confirmation of HNSCC as an important group of HPV-related human malignancies. Summary: In this review, the authors first describe the scope (i.e., HNSCC) by the anatomic sites of the tumors. Their important site-specific differences in epidemiology are emphasized, and the misconceptions caused by the adopted practice of pooling all tumors from these divergent anatomic sites as a single entity (HNSCC) are pinpointed. The convincing evidence of the established risk factors (smoking and alcohol) is briefly addressed, before entering in the discussion on the causal role of HPV in HNSCC pathogenesis. The global HPV prevalence in different subsets of HNSCC is summarized using the data extracted from all meta-analyses published since 2010. Of all HNSCC subsets, oropharyngeal SCC has an HPV profile distinct form all the other subsets, and the possible mechanisms explaining this intimate association with HPV are discussed. Key Messages: Recent global trends show a constant increase in HNSCC rates particularly among younger age groups. The evidence on cigarette smoking and alcohol consumption as the prime risk factors of HNSCC is overwhelming. During the past 35 years, however, increasing evidence has accumulated implicating an important causal role of HPV in HNSCC. These data have important clinical implications, HPV detection and tailored treatment strategies for HPV-positive HNSCCs currently being an integral part of the oncological management practices of HNSCC.
We describe a case of cerebrospinal fluid pleocytosis in a previously well infant after his first immunisation with the multicomponent meningococcal serogroup B and advice clinicians to be cautious with the interpretation of CSF findings in children post Meningococcal B vaccination until clearer guidelines are available Keywords: meningococcal B vaccine - cerebrospinal fluid pleocytosis - inflammatory response - infant.
Objective
To evaluate the association between cervical human papillomavirus (HPV) infection at the time of admission and the presence of microbial invasion of the amniotic cavity (MIAC) and intra-amniotic inflammation (IAI) in women with preterm prelabor rupture of membranes (PPROM) and to determine the association between cervical HPV infection and short-term neonatal morbidity.
Methods
One hundred women with singleton pregnancies complicated by PPROM between the gestational ages of 24+0 and 36+6 weeks were included in the study. The presence of HPV DNA was evaluated in scraped cervical cells using polymerase chain reaction (PCR). Amniotic fluid samples were obtained by transabdominal amniocentesis.
Results
The rate of cervical HPV infection in women with PPROM was 24%. The rates of MIAC and IAI were not different between women with cervical HPV infection and those without cervical HPV infection [MIAC: with HPV: 21% (5/24) vs. without HPV: 22% (17/76), p = 1.00; IAI: with HPV: 21% (5/24) vs. without HPV: 18% (14/76), p = 0.77]. There were no differences in the selected aspects of short-term neonatal morbidity between women with and without cervical HPV infection.
Conclusions
In women with PPROM, the presence of cervical HPV infection at the time of admission is not related to a higher risk of intra-amniotic infection-related and inflammatory complications or worse short-term neonatal outcomes.
Papillomaviruses are one of the oldest viruses known, dating back 330 million years. During this long evolution, human papillomaviruses (HPV) have developed into hijackers of human cellular and immune systems in which they replicate and remain silent. Systematic studies on oral HPV infections and their outcomes are still scarce. Oral HPV infections have been linked to sexual behaviour, but recent evidence supports their horizontal, mouth‐to‐mouth, transmission. Most HPV infections in infants are acquired vertically from the mother during the intrauterine period, during delivery, or later via saliva. The best‐known benign clinical manifestations of HPV infection are oral papilloma/condyloma and focal epithelial hyperplasia. Evidence is emerging which suggests that some oral HPV infections might persist. Persistent HPV infection is mandatory for HPV‐associated malignant transformation. However, progression of HPV‐induced lesions to malignancy requires additional cofactors. In the early 1980s, we provided the first evidence that a subset of oral cancers and other head and neck cancers might be causally linked to HPV infection. This review summarizes current knowledge on the virus itself, its transmission modes, as well as the full spectrum of oral HPV infections – from asymptomatic infections to benign, potentially malignant oral lesions, and squamous cell carcinoma.
Recurrent respiratory papillomatosis (RRP) is a disease that is characterized by recurrent growth of exophytic wart-like lesions throughout the respiratory tract. The disease is mainly associated with low-risk human papillomavirus (HPV) types 6 and 11. The distribution of the age of onset of RRP shows three peaks: age 4 years old, age 34, and age 60–64. Patients with RRP generally experience voice problems and without treatment, eventually develop a compromised airway. Owing to the recurrent character of RRP, most patients require repeated surgical interventions to remove the lesions to keep the voice functional and the airway patent. There is currently no cure for RRP. This chapter reviews the etiology, diagnosis, therapeutic options, and prevention of RRP.
We identified the novel HLA-G*01:21N null allele in Finnish Caucasian individuals.
Background:
HPV DNA has been detected in breast milk but its origin has remained obscure. The aim of the study was to analyze the prevalence and persistence of HPV in breast milk in the Finnish Family HPV cohort study. The association of breast milk HPV positivity with the family members' oral HPV status was evaluated.
Methods:
We included 308 families to the study where the mother was breast feeding her offspring. Mothers collected the milk samples manually at day 3, and at months 2, 6 and 12. Cervical and/or oral samples were collected from all family members. HPV testing was performed using nested PCR and Luminex-based Multimetrix kit.
Results:
Breast milk HPV DNA was found in 10.1% (31/308), 20.1% (39/194) and 28.8% (17/59) of samples at day 3, month 2 and -6, respectively. The following HPV genotypes were detected: 6,16,18,33,45,53,56,59,66 and 82. Breast milk HPV persisted among 5.5%(9/164) of the lactating mothers. No significant associations were detected between the persistent breast milk HPV and the offspring's oral incident HPV infection. Breast milk HPV positivity showed a strong association with the fathers' oral HPV positivity at baseline, as well as at 6- and 12- month FU visits, with OR=3.24 (95% CI 1.04-10.12), OR=6.34 (95% CI 1.84-21.89) and OR=14.25 (95% CI 1.16-174.80),respectively.
Conclusions:
HPV in breast milk is prevalent among the lactating mothers and HPV can also persist in breast milk. The breast milk is a potential vehicle for HPV transmission to oral mucosa of the spouse but not of the offspring.
HPV-associated head and neck squamous cell carcinoma (HNSCC), more specifically the incidence of oropharyngeal cancer, is dramatically increasing in industrialized countries. According to what has been learned from anogenital vaccination programs, there are reasons to believe that current human papillomavirus (HPV) vaccinations may be potentially effective also against HNSCC. However, before specific results on HNSCC are available, one must keep in mind that carcinogenesis in the head and neck region may differ from that of the anogenital tract. Furthermore, the current evidence supports the view that HPV infection is much more complex than simply a sexually transmitted disease. HPV is present in the semen, placenta and in the newborns, and these infections of the newborns create cell-mediated immunity (CMI) against HPV, including the T memory cells. Acquisition of HPV infection in early life will rise new series of questions in the field of HPV vaccination.
The objective of the study is to determine the prevalence of high-risk human papillomavirus (hrHPV) infection in tonsillar swabs and tissue
Patients undergoing tonsillectomy for nonmalignant causes were enrolled. A flocked swab and fresh tissue were collected from the left and right tonsil of each patient. Specimens were tested for hrHPV DNA using the Roche cobas test and for the presence of E6/E7 messenger RNA using the Hologic Aptima hrHPV test.
Of the 193 patients enrolled, 129 were in the pediatric group (ages 1–12 years; median, 5 years), and 64 were in the adult group (ages 13–55; median, 22 years). All swab and tissue specimens were negative for hrHPV by both methods. Positive, negative, and internal controls performed as expected.
We found a 0% rate of infection indicating that detectable hrHPV infection in tonsillar tissue appears to be uncommon in the children and adults in the population sampled.
Few large studies have evaluated concordance based on a broad spectrum of human papillomavirus (HPV) types in oral and genital specimens of mothers and their recently born infants. This information is important in determining whether HPV vaccines administered prior to pregnancy may be useful for preventing vertical transmission. HPV DNA was positive in 30% of mothers and 1.5% of newborns. Maternal/newborn concordance (HPV+/+ or HPV-/-) was 71%. Among HPV DNA+ mothers, only 3% of their infants were DNA+ and only 1 pair had the same HPV type. Among HPV- women, 0.8% of infants were HPV+. HPV DNA detected in hospitalized newborns reflects current infection transmitted to infants during pregnancy or delivery. None of the mother/baby HPV DNA+ concordance pairs detected viral types found in HPV vaccines suggesting that vaccination prior to pregnancy is unlikely to be efficacious in preventing vertical transmission.
The purpose was to study the perinatal transmission of human papillomavirus DNA (HPV-DNA) in 63 mother-newborn pairs, besides looking at the epidemiological factors involved in the viral DNA transmission. The following sampling methods were used: (1) in the pregnant woman, when was recruited, in cervix and clinical lesions of the vagina, vulva and perineal region; (2) in the newborn, (a) buccal, axillary and inguinal regions; (b) nasopharyngeal aspirate, and (c) cord blood; (3) in the children, buccal was repeated in the 4th week and 6th and 12th month of life. HPV-DNA was identified using two methodologies: multiplex PCR (PGMY09 and MY11 primers) and nested-PCR (genotypes 6/11, 16, 18, 31, 33, 42, 52 and 58). Perinatal transmission was considered when concordance was found in type-specific HPV between mother/newborn or mother/child. HPV-DNA genital was detected in 49 pregnant women submitted to delivery. Eleven newborns (22.4%, n = 11/49) were HPV-DNA positive. In 8 cases (16.3%, n = 8/49) there was type specific HPV concordance between mother/newborn samples. At the end of the first month of life three children (6.1%, n = 3/49) became HPV-DNA positive, while two remained positive from birth. In 3 cases (100%, n = 3/3) there was type specific HPV concordance between mother/newborn samples. In the 6th month, a child (2%, n = 1/49) had become HPV-DNA positive between the 1st and 6th month of life, and there was type specific HPV concordance of mother/newborn samples. All the HPV-DNA positive children (22.4%, n = 11/49) at birth and at the end first month of life (6.1%, n = 3/49) became HPV-DNA negative at the age of 6 months. The HPV-DNA positive child (2%, n = 1/49) from 1st to the 6th month of life became HPV-DNA negative between the 6th and 12th month of life and one child had anogenital warts. In the twelfth month all (100%, n = 49/49) the children studied were HPV-DNA negative. A positive and significant correlation was observed between perinatal transmission of HPV-DNA and the immunodepression of maternal variables (HIV, p = 0.007). Finally, the study suggests that perinatal transmission of HPV-DNA occurred in 24.5% (n = 12/49) of the cases studied.
Studies on HPV infection in pregnant women and HPV transmission to the child have yielded inconsistent results.
To estimate mother-to-child HPV transmission we carried out a prospective cohort study that included 66 HPV-positive and 77 HPV-negative pregnant women and their offspring attending a maternity hospital in Barcelona. To estimate HPV prevalence and genotype distribution in pregnancy we also carried out a related screening survey of cervical HPV-DNA detection among 828 pregnant women. Cervical cells from the mother were collected at pregnancy (mean of 31 weeks) and at the 6-week post-partum visit. Exfoliated cells from the mouth and external genitalia of the infants were collected around birth, at the 6-week post-partum visit, and around 3, 6, 12, and 24 months of age. All samples were tested for HPV using PCR. Associations between potential determinants of HPV infection in pregnant women and of HPV positivity in infants were also explored by logistic regression modelling.
Overall cervical HPV-DNA detection in pregnant women recruited in the HPV screening survey was 6.5% (54/828). Sexual behavior-related variables, previous histories of genital warts or sexually transmitted infections, and presence of cytological abnormalities were statistically significantly and positively associated with HPV DNA detection in pregnant women recruited in the cohort. At 418 infant visits and a mean follow-up time of 14 months, 19.7% of infants born to HPV-positive mothers and 16.9% of those born to HPV-negative mothers tested HPV positive at some point during infants' follow-up. The most frequently detected genotype both in infants and mothers was HPV-16, after excluding untyped HPV infections. We found a strong and statistically significant association between mother's and child's HPV status at the 6-week post-partum visit. Thus, children of mothers' who were HPV-positive at the post-partum visit were about 5 times more likely to test HPV-positive than children of corresponding HPV-negative mothers (p = 0.02).
This study confirms that the risk of vertical transmission of HPV genotypes is relatively low. HPV persistence in infants is a rare event. These data also indicate that vertical transmission may not be the sole source of HPV infections in infants and provides partial evidence for horizontal mother-to-child HPV transmission.
We determined L1 antibodies for human papillomavirus (HPV) types 6, 11, 16, 18 and 45 by multiplex serology in our prospective HPV family study. We report seroprevalence, seroconversion and antibody decay in 290 women (mean age, 25.5 years) sampled before delivery and at 12, 24 and 36 months of follow-up. Multiplex HPV genotyping of the baseline oral and genital scrapings was performed. At baseline, seroprevalence of HPV 6, 11, 16, 18 and 45 was 53.3, 21.5, 34.9, 21.5 and 9.0%, respectively. Seropositivity for low-risk HPV (LR-HPV) was associated significantly with age at onset of sexual activity (P=0.001), number of sexual partners until age 20 (P=0.018), lifetime number of sexual partners (P=0.0001), history of genital warts (P=0.0001) and being seropositive for high-risk (HR) HPV (P=0.0001). The same covariates also predicted seropositivity for HR-HPV. During follow-up, 26.7, 13.9, 17.0, 16.8 and 6.6% of the women seroconverted to L1 antigen of HPV 6, 11, 16, 18 and 45, respectively, between 18.2 and 23.8 months. Independent predictors of seroconversion to LR-HPV were unemployment (P=0.019) and absence of anal sex practice (P=0.031), and to HR-HPV, absence of smoking history and lifetime number of sexual partners. Decay of HPV 6, 11, 16, 18 and 45 antibodies was observed in 2.3, 4.0, 5.3, 4.5 and 1.5 % of the women, respectively, with decay time varying from 27.2 to 35.8 months. These data imply that (i) a substantial proportion of young women are seropositive for both LR- and HR-HPV types, (ii) they frequently undergo seroconversion within 18-24 months, predicted by common covariates, and (iii) antibody decay over 3 years is rare.
Human papilloma viruses (HPV) are common pathogens associated with a wide range of cutaneous and mucosal infections in childhood. Different HPV types can cause common warts, genital warts, low-grade as well as high-grade squamous intraepithelial lesions. Anogenital warts represent an issue with legal and clinical implications and evaluation of children for the possibility of sexual abuse should be considered in all cases. Recurrent respiratory papillomatosis has also been associated with HPV infection in a variety of studies. The recently introduced HPV vaccination is expected to prevent HPV-related cervical cancer in adulthood; however, HPV infection will continue to affect children.
This paper aimed at studying the transplacental transmission of HPV and looking at the epidemiological factors involved in maternal viral infection. The following sampling methods were used: (1) in the pregnant woman, (a) genital; (b) peripheral blood; (2) in the newborn, (a) oral cavity, axillary and inguinal regions; (b) nasopharyngeal aspirate, and (c) cord blood; (3) in the placenta. The HPV DNA was identified using two methods: multiplex PCR of human beta-globin and of HPV using the PGMY09 and PGMY11 primers; and nested-PCR, which combines degenerated primers of the E6/E7 regions of the HPV virus, that allowed the identification of genotypes 6/11, 16, 18, 31, 33, 42, 52 and 58. Transplacental transmission was considered when type-specific HPV concordance was found between the mother, the placenta and the newborn or the mother and cord blood. The study included 49 HPV DNA-positive pregnant women at delivery. Twelve placentas (24.5%, n = 12/49) had a positive result for HPV DNA. Eleven newborn were HPV DNA positive in samples from the nasopharyngeal or buccal and body or cord blood. In 5 cases (10.2%, n = 5/49) there was HPV type-specific agreement between genital/placenta/newborn samples. In one case (2%, n = 1/49) there was type specific HPV concordance between genital/cord blood and also suggested transplacental transmission. A positive and significant correlation was observed between transplacental transmission of HPV infection and the maternal variables of immunodepression history (HIV, p = 0.011). In conclusion the study suggests placental infection in 23.3% of the cases studied and transplacental transmission in 12.2%. It is suggested that in future HPV DNA be researched in the normal endometrium of women of reproductive age. The possible consequence of fetal exposure to HPV should be observed.
To date, more than 100 types of human papillomavirus (HPV) have been identified. In the past 20 years, there has been an increasing interest in HPVs because of their potential role in the pathogenesis of malignant tumors. HPV infections are known to affect predominantly adult, sexually active age groups, whereas skin warts, at various anatomic sites, are usually associated with younger individuals. The modes of viral transmission in children remain controversial, including perinatal transmission, auto- and hetero-inoculation, sexual abuse, and, possibly, indirect transmission via fomites. Recent studies on perinatal infection with HPV have been inconclusive. It is still unclear how frequently perinatal infection progresses to clinical lesions, whether genital, laryngeal, or oral. Conflicting reports have been published on the prevalence of HPV infections in children. The current consensus is, however, that newborn babies can be exposed to cervical HPV infection of the mother. The detection rate of HPV DNA in oral swabs of newborn babies varies from 4% to 87%. The concordance of HPV types detected in newborn babies and their mothers is in the range of 57% to 69%, indicating that the infants might acquire the HPV infection post-natally from a variety of sources. HPV antibodies have been detected in 10% to 57% of the children, and there is usually no correlation between seropositivity and the detection of HPV DNA in either the oral or the genital mucosa. There is also evidence that transmission in utero or post-natal acquisition is possible. The mode of in utero transmission remains unknown, but theoretically the virus could be acquired hematogenously, by semen at fertilization, or as an ascending infection in the mother. The understanding of viral transmission routes is important, particularly because several vaccination programs are being planned worldwide. The serologic response to HPV detected in different populations of young women or women at risk of cervical cancer might be due to genital infections, but the possibility that HPV infection has been acquired earlier in life through the oral mucosa or respiratory tract cannot be ruled out.
The Finnish HPV Family Study is a prospective cohort study assessing the dynamics of human papillomavirus (HPV) transmission between parents and infant. Serial genital and oral scrapings from 76 families, including mother, father, and infant, and semen samples were collected over 2 years of follow-up, analyzed by nested PCR, and confirmed by hybridization with 12 high-risk (HR) HPV types. The most common HPV profile was HR HPV in all family members (29%), followed by HPV-positive mother-infant pairs (26%). HPV-positive father-infant pairs were less frequent (11%), and in six (8%) families, only the infant was HR HPV positive. The prevalence of genital HR HPV in the parents ranged from 13 to 25%, and that of oral HPV ranged from 8 to 34%. In the infants, HPV DNA was detected in 15% of the genital and 10% of the oral samples at birth, reaching peaks of 18 and 21%, respectively, at 6 months, and declining to 10% at 24 months. Persistent HPV in the mother was a risk factor for oral HPV in the infant (odds ratio [OR], 5.69; 95% confidence interval [95% CI], 1.5 to 21.3), while oral HPV in the mother at 6 months was a risk factor for genital HR HPV (OR, 6.38; 95% CI, 1.15 to 35.32). No such independent risk could be attributed to subclinical HPV in the father. Persistent maternal cervical HPV and subclinical oral HPV affect the risk of infant HPV. The age of 6 months is a critical point for the infant to acquire or be free of HR HPV DNA.
In order to better understand the exact mode and risk of vertical transmission in asymptomatic pregnant women, as well as the relationship between HPV transmission and mode of delivery, we have proposed this systematic quantitative review of prospective cohort studies. A comprehensive search was performed in the Cochrane Library, MEDLINE, LILACS, CANCERLIT, and EMBASE, as well as in the reference lists from the identified studies. Nine primary studies, which included 2,111 pregnant women and 2,113 newborns, met our selection criteria and were analyzed. A positive HPV test in the mother increased the risk of vertical HPV transmission (RR: 4.8; 95%CI: 2.2-10.4). We also observed a higher risk of HPV infection after vaginal delivery than after cesarean section (RR: 1.8; 95%CI: 1.3-2.4). The results of this meta-analysis showed the HPV DNA-positive rate only after birth, but an HPV DNA-positive neonatal sample does not necessarily indicate infection; it could merely indicate contamination (perinatal HPV contamination may have occurred). Infants born through vaginal delivery were at higher risk of exposure to HPV.
More than 100 different human papillomaviruses (HPVs) can cause proliferative diseases, many of which are malignant, such as cervical cancer. HPV serology is complex because infection and disease lead to distinct type-specific antibody responses. Using bead-based technology, we have developed an assay platform that allows the simultaneous detection of antibodies against up to 100 in situ affinity-purified recombinant HPV proteins.
Twenty-seven HPV proteins were expressed as glutathione S-transferase fusion proteins and affinity-purified in one step by incubation of glutathione-displaying beads in bacterial lysate. Spectrally distinct bead sets, each carrying one particular antigen, were mixed, incubated with serum, and differentiated in a flow cytometer-like analyzer (xMAP; Luminex Corp). Antibodies bound to the antigens were detected via fluorescent secondary reagents. We studied 756 sera from 2 case-control studies of cervical cancer.
Glutathione S-transferase fusion proteins bound with high affinity to glutathione-displaying beads (Kd = 6.9 x 10(-9) mol/L). The dynamic range of multiplex serology covered 1.5 orders of magnitude, and antibodies were detected at serum dilutions >1:1,000,000. Imprecision (median CV) was < or = 5.4%, and assay reproducibility was high (R2 = 0.97). Results on clinical samples showed high concordance with ELISA (kappa = 0.846), but multiplex serology exhibited increased detection of weak antibody responses. Antibodies to the E6 oncoproteins of the rare HPV types 52 and 58 were associated with cervical cancer (P < 0.001).
Multiplex serology enables antibody analyses of large numbers of sera against up to 100 antigens in parallel and has the potential to replace ELISA technology.
Human papillomavirus (HPV) has recently been associated with oral cancers. To prepare for a study of the natural history of oral HPV infection, the effect of the DNA purification method on HPV genomic DNA detection in Scope mouthwash oral rinse samples and the reproducibility of HPV detection in rinse samples collected 7 days apart were investigated. The study was conducted with a population at high risk for oral HPV infection: human immunodeficiency virus-infected men with CD4-cell counts <200. Five DNA purification methods were compared among equal aliquots of oral rinse samples collected from a subset of individuals. The purification methods included (i) proteinase K digestion (PKD) and heat inactivation; (ii) PKD and ethanol precipitation (EP); (iii) PKD, phenol-chloroform extraction, and EP; (iv) use of the Puregene DNA purification kit; and (v) use of the QIAamp DNA Blood Midi kit. HPV was detected by PCR amplification with PGMY09 and PGMY11 L1 primer pools and by use of a Roche linear array. Puregene-purified samples had higher human DNA yields and purities, and Puregene purification detected the greatest number of HPV-positive subjects and total HPV infections in comparison to the numbers detected by all other methods. The total number of HPV infections and HPV prevalence estimates were also higher for Puregene-processed oral rinse samples when a fixed volume (10 mul) rather than a fixed cell number ( approximately 50,000 cells) was used for PCR amplification. A good concordance was observed for oral HPV infection status (agreement, 80%; kappa value, = 0.60) and type-specific infection (agreement, 98%; kappa value, 0.57) in matched oral rinse samples. The method of DNA purification significantly affects the detection of HPV genomic DNA from oral rinse samples and may result in exposure misclassification that could contribute to the inconsistent associations reported in the literature.
This study is aimed to clarify data on the acquisition, persistence, and clearance of high-risk types of human papillomavirus (HPV) DNA from the mucosa and the determinants of persistent mucosal HPV infection in infants.
Oral and genital scrapings from 324 infants were collected at birth, 3 days after delivery, and 1, 2, 6, 12, 24, and 36 months after delivery and tested for the presence of HPV DNA by nested polymerase chain reaction and hybridization with 12 high-risk HPV oligoprobes. HPV status and demographic data for parents were analyzed.
During the follow-up period (median duration, 26.2 months), HPV DNA was found to be present in 12%-21% of oral scrape samples and in 4%-15% of genital scrape samples obtained from the infants. Oral HPV infection was acquired by 42% of children, cleared by 11%, and persisted in 10% of the infants, whereas 37% were never infected. The corresponding figures for genital HPV infection were 36%, 14%, 1.5%, and 47%. Kaplan-Meier analysis revealed that both the cumulative incidence of infection and clearance of HPV were parallel in oral and genital sites. Persistent oral HPV infection in the child was significantly associated with persistent oral HPV infection in the mother at month 36 of follow-up, hand warts in the mother, young age at onset of sexual activity for the mother, and the mother's use of oral contraception, as well as with the father's oral HPV status at 24 months. Persistent genital HPV infection in the infant was predicted by if the mother had started smoking at 18-21 years of age and by a history of genital warts.
Persistent carriage of high-risk HPV types was detected in oral and genital mucosa specimens obtained from 10% and 1.5% of the infants during their first 26 months of life. The rates of acquisition and clearance of HPV were similar in oral and genital mucosa.
Typing of human papillomaviruses (HPV) by DNA hybridization procedures, such as reverse line blot (RLB) assay, is sensitive and well validated. However, the application of these assays to high-throughput analyses is limited. Here, we describe the development of multiplex human papillomavirus genotyping (MPG), a quantitative and sensitive high-throughput procedure for the identification of multiple high- and low-risk genital HPV genotypes in a single reaction. MPG is based on the amplification of HPV DNA by a general primer PCR (GP5+/6+) and the subsequent detection of the products with type-specific oligonucleotide probes coupled to fluorescence-labeled polystyrene beads (Luminex suspension array technology). Up to 100 different HPV types can be detected simultaneously with MPG, and the method is fast and labor saving. We detected all 22 HPV types examined with high specificity and reproducibility (the median interplate coefficient of variation was below 10%). Detection limits for the different HPV types varied between 100 and 800 pg of PCR products. We compared the performance of MPG to an established RLB assay on GP5+/6+-PCR products derived from 94 clinical samples. The evaluation showed an excellent agreement (kappa = 0.922) but also indicated a higher sensitivity of MPG. In conclusion, MPG appears to be highly suitable for large-scale epidemiological studies and vaccination trials as well as for routine diagnostic purposes.
Type-specific antibodies to human papillomaviruses (HPVs) can be detected in most infected adult patients, and they have virus-neutralizing properties. However, there is a dearth of information on the seroprevalence of maternal and neonatal antibodies to HPV capsid antigens. Sera from 104 mothers, their newborns, and 3 twin pregnancies were analyzed by an enzyme-linked immunosorbent assay (ELISA) for the presence of specific IgG, IgM, and IgA antibodies to virus-like particles of HPV-6, -11, -16, -18, and -31. Maternal IgG positivity rates to HPV types 6, 11, 16, 18, and 31 were 23.1%, 2.9%, 8.7%, 5.8%, and 9.6%, respectively. Neonatal rates did not differ significantly, and individual IgG ELISA values of mothers and their infants and all paired twins showed a very high correlation. In contrast, nearly all IgM and IgA individual values in newborns were designated negative, whereas mothers' positivity rates ranged as high as 19.2%. Infants showed no HPV-related lesions at birth or at 4-year follow-up. Seven of 8 tested children lost IgG HPV antibodies in a follow-up examination. Similar anti-HPV IgG seropositivity in mothers and newborns and a lack of neonatal IgA and IgM together with twin and follow-up results indicate that neonatal IgG is not a sign of intrauterine HPV infection but, rather, maternofetal antibody transmission.
The natural history of infections with many human papillomavirus (HPV) types is poorly understood. Here, we describe for the first time the age- and sex-dependent antibody prevalence for 29 cutaneous and five mucosal HPV types from 15 species within five phylogenetic genera (alpha, beta, gamma, mu, nu) in a general population. Sera from 1,797 German adults and children (758 males and 1,039 females) between 1 and 82 years (median 37 years) were analysed for antibodies to the major capsid protein L1 by Luminex-based multiplex serology. The first substantial HPV antibody reactions observed already in children and young adults are those to cutaneous types of the genera nu (HPV 41) and mu (HPV 1, 63). The antibody prevalence to mucosal high-risk types, most prominently HPV 16, was elevated after puberty in women but not in men and peaked between 25 and 34 years. Antibodies to beta and gamma papillomaviruses (PV) were rare in children and increased homogeneously with age, with prevalence peaks at 40 and 60 years in women and 50 and 70 years in men. Antibodies to cutaneous alpha PV showed a heterogeneous age distribution. In summary, these data suggest three major seroprevalence patterns for HPV of phylogenetically distinct genera: antibodies to mu and nu skin PV appear early in life, those to mucosal alpha PV in women after puberty, and antibodies to beta as well as to gamma skin PV accumulate later in life.
We investigate the contribution of the Iberian bat fauna to the cryptic diversity in Europe using mitochondrial (cytb and ND1) and nuclear (RAG2) DNA sequences. For each of the 28 bat species known for Iberia, samples covering a wide geographic range within Spain were compared to samples from the rest of Europe. In this general screening, almost 20% of the Iberian species showed important mitochondrial discontinuities (K2P distance values > 5%) either within the Iberian or between Iberian and other European samples. Within Eptesicus serotinus and Myotis nattereri, levels of genetic divergence between lineages exceeded 16%, indicating that these taxa represent a complex of several biological species. Other well-differentiated lineages (K2P distances between 5–10%) appeared within Hypsugo savii, Pipistrellus kuhlii and Plecotus auritus, suggesting the existence of further cryptic diversity. Most unsuspected lineages seem restricted to Iberia, although two have crossed the Pyrenees to reach, at leas...
Objective:
To analyze human papillomavirus (HPV) DNA in umbilical cord blood and in placenta, including its cellular localization.
Design:
Longitudinal prospective study.
Setting:
Maternity Unit of Turku University Hospital, and MediCity, University of Turku.
Samples:
Placental and cord blood samples obtained at delivery from 315 mothers and 311 neonates included in the Finnish HPV Family Study.
Methods:
HPV testing by nested PCR and sequencing. Tyramide amplified in situ hybridization (ISH) for viral DNA localization in placenta. Correlation to mother's and neonate's oral and genital HPV status and maternal demographic data.
Main outcome measures:
Detection and cellular localization of HPV DNA.
Results:
HPV DNA was detected in 4.2 and 3.5% of placenta and cord blood samples, respectively, including HPV types 16, 6, 83 and 39. In placenta, HPV6 and 16 DNA was localized in syncytiotrophoblasts. Abnormal cytology increased the risk of HPV+ placenta and cord blood. History of genital warts was the only independent predictor of cord blood HPV in multivariate analysis (adjusted OR=4.0, 95% CI: 1.09-14.54, p=0.036). HPV DNA in cord blood increased the risk of genital (OR=4.0, 95% CI: 1.08-14.83, p=0.048) and oral (OR=4.4, 95% CI: 1.17-16.14, p=0.039) HPV DNA carriage of the neonate. HPV+ placenta increased the risk of oral HPV of the neonate (OR=8.6, 95% CI: 2.73-27.13, p=0.0001). Delivery mode did not predict HPV status of the neonate.
Conclusions:
HPV DNA is detected in placental trophoblasts and umbilical cord blood. The presence of HPV DNA at these sites increases the risk of a neonate testing HPV-positive at birth.
Perinatal transmission of genital human papillomaviruses (HPVs), including HPV-16 and -18 which are associated with anogenital carcinomas have been described previously [Pakarian et al. (1994): British Journal of Obstetrics and Gynaecology 101:514-517; Kaye et al. (1994) Journal of Medical Virology 44:415-421]. A study was undertaken to investigate whether HPV-16 and -18 DNA in infants contaminated at delivery persists until they are 6 months of age. Of 61 pregnant women recruited, 42 (68.8%) were HPV-16 and 13 (21.3%) were HPV-18 DNA positive. At 24 hr there were transmission rates from HPV DNA positive mothers to their infants of about 73% (HPV-16: 69%; HPV-18: 76.9%). Ten mothers who were both HPV-16 and -18 DNA positive produced six (60%) infants who were also doubly positive at 24 hr. HPV DNA persisted to 6 weeks in 79.5% (HPV-16: 84%; HPV-18: 75%) of those infants who were positive at birth. At 6 months of age, persistent HPV-16 DNA was detected in 83.3% of cases, but HPV-18 DNA persistence at this time was 20%. To extend these observations over a greater age range of children HPV-16 L1 and L2 proteins were expressed in insect cells via recombinant baculoviruses and sera from 229 children were examined to determine at what age IgM antibodies to HPV were acquired. There was a bimodal distribution of IgM seropositivity which peaked between 2 and 5 and 13 and 16 years of age, suggesting that two distinct modes of transmission may occur. The observation that infection with high cancer risk genital HPVs may occur in early life and persist is of considerable importance for HPV vaccine strategies. © Wiley-Liss, Inc.
Objective To demonstrate the perinatal transmission and persistence of the cancer associated human papillomavirus types 16, 18, 31 and 33.Design Cervical swabs were taken from pregnant women between 20 and 38 weeks of gestation. Buccal and genital swabs were taken from infants at 24 h and at six weeks after delivery and examined for HPV-16, -18,–31 and –33 DNA by the polymerase chain reaction.Setting Maternity Unit at St Thomas' Hospital, London.Subjects Thirty-one pregnant women, 16 with a previous history of cervical intraepithelial neoplasia or genital warts, or both, and their 32 infants (one set of twins).Results Twenty of the 31 (65 %) women were positive for HPV-DNA prior to delivery. Twelve of 32 (38%) and eight of 31 (26%) infants were HPV-DNA positive at 24 h and six weeks respectively. Swabs taken at 24 h demonstrated HPV type 16 in five mother-infant pairs and HPV type 18 in two mother-infant pairs. Dual infections with HPV types 16 and 18 were demonstrated in swabs from three mother-infant pairs. At six weeks, HPV-16 was demonstrated in swabs from six infants and HPV-18 in swabs from two infants.Conclusions Perinatal transmission of human papillomavirus types 16 and 18 occurred in 55% cases. Persistent human papillomavirus infection was demonstrated at six weeks of age. Whether acquisition of human papillomavirus during the perinatal period predisposes to an increased risk of cervical intraepithelial neoplasia among female infants in later life remains to be established. Information on the persistence of perinatally acquired human papillomavirus is required before rational vaccination programmes can be considered.
Syrjänen S. Current concepts on human papillomavirus infections in children. APMIS 2010; 118: 494–509.
Current evidence is strong enough to conclude that human papillomavirus (HPV) can be transmitted both sexually and non-sexually. The debate on HPV infections in children still continues but it is more focused on HPV prevalence than on transmission modes. HPV DNA detection in amniotic fluid, foetal membranes, cord blood and placental trophoblastic cells all suggest HPV infection in utero, i.e. prenatal transmission. Based on recent meta-analysis, vertical transmission occurs in approximately 20% of cases. Most of the mucosal HPV infections in infants are incident, persistent infections in oral and genital mucosa being found in less than 10% and 2% respectively. The mother seems to be the main transmitter of HPV to her newborn, but subsequent HPV infections are acquired horizontally via saliva or other contacts. Bimodal peak prevalence is seen for skin warts, oral papillomas and recurrent respiratory papillomatosis (RRP) in younger and older age groups, suggesting similar epidemiology. Of the clinical HPV diseases, juvenile-onset-RRP and genital condylomata are problematic; the former because of its life-threatening potential and the latter because of possible sexual abuse. HPV6 and 11 are the most common genotypes in both the lesions. Early in life, infections by the high-risk HPV genotypes may also remain persistent for a considerable period, and should be of considerable importance for HPV vaccination strategies.
The objective of this study was to examine the possibility of intrauterine human papillomavirus infection of fetuses by transplacental transmission of human papillomavirus before delivery.
Specimens of cervicovaginal cells and peripheral blood mononuclear cells were obtained from 52 consecutive pregnant women in the third trimester of pregnancy. Cord blood specimens were also obtained from the neonates born to these mothers. Presence of human papillomavirus types 16 and 18 deoxyribonucleic acid was analyzed by an in vitro enzymatic deoxyribonucleic acid amplification method.
Human papillomavirus type 16 deoxyribonucleic acid was found in 6 (11.5%) cervicovaginal and in 9 (17.3%) peripheral blood mononuclear cell specimens. Seven cord blood specimens from neonates born to mothers who were positive for peripheral blood mononuclear cell human papillomavirus type 16 deoxyribonucleic acid were found to contain human papillomavirus type 16 deoxyribonucleic acid. One cervicovaginal and two peripheral blood mononuclear cell specimens contained human papillomavirus type 18 deoxyribonucleic acid, but none of the cord blood specimens contained human papillomavirus type 18 deoxyribonucleic acid.
These results seem to suggest possible transplacental transmission of the virus and the potential association of such transmission with the status of human papillomavirus in peripheral blood mononuclear cells.
The presence of human papillomavirus (HPV) types 2, 6, 7, 11, 13 and 16 DNA in cytologic scrapings of oral mucosa was studied in 309 women with genital HPV infections. The objective was to test the usefulness of oral mucosal scrapings (3 sequential swabs) in HPV DNA detection by dot blot hybridization. Based on hybridization with the 32P-labelled Alu-repeat probe, most samples contained more than 10(5) cells, which is an adequate number of cells for dot blot hybridization. Hybridization with 32P-labelled HPV DNA probes showed that 3.8% of the 309 women had an oral HPV infection. Of these, only 2 had clinical lesions indicative of HPV. All other oral HPV positive subjects had clinically healthy mucosa. HPV 6 was the most common (3.1%) type, followed by HPV 11 and 16 (1.1%). In 3 cases the genital mucosa harboured the same HPV type as found in the oral cavity. The results indicate that oral mucosal scraping results in adequate number of cells for dot blot hybridization with HPV DNA. Although the method is likely to result in an underestimation of latent and subclinical HPV infections, it is useful for studying the clinical HPV infections as well as other viral infections known to be present in exfoliated cells.
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To demonstrate the perinatal transmission and persistence of the cancer associated human papillomavirus types 16, 18, 31 and 33.
Cervical swabs were taken from pregnant women between 20 and 38 weeks of gestation. Buccal and genital swabs were taken from infants at 24 h and at six weeks after delivery and examined for HPV-16, -18, -31 and -33 DNA by the polymerase chain reaction.
Maternity Unit at St Thomas's Hospital, London.
Thirty-one pregnant women, 16 with a previous history of cervical intraepithelial neoplasia or genital warts, or both, and their 32 infants (one set of twins).
Twenty of the 31 (65%) women were positive for HPV-DNA prior to delivery. Twelve of 32 (38%) and eight of 31 (26%) infants were HPV-DNA positive at 24 h and six weeks respectively. Swabs taken at 24 h demonstrated HPV type 16 in five mother-infant pairs and HPV type 18 in two mother-infant pairs. Dual infections with HPV types 16 and 18 were demonstrated in swabs from three mother-infant pairs. At six weeks, HPV-16 was demonstrated in swabs from six infants and HPV-18 in swabs from two infants.
Perinatal transmission of human papillomavirus types 16 and 18 occurred in 55% cases. Persistent human papillomavirus infection was demonstrated at six weeks of age. Whether acquisition of human papillomavirus during the perinatal period predisposes to an increased risk of cervical intraepithelial neoplasia among female infants in later life remains to be established. Information on the persistence of perinatally acquired human papillomavirus is required before rational vaccination programmes can be considered.
This study determined the prevalence of human papillomavirus 16/18 DNA in deparaffinized oral carcinoma specimens on slides with the use of the different sensitivities of in situ hybridization and a technique that combines polymerase chain reaction and in situ hybridization. Human papillomavirus DNA was not detected in the 30 biopsy specimens analyzed by in situ hybridization alone using biotinylated DNA probes specific for human papillomavirus 16/18. Twenty of 30 specimens (66.7%) were found to have human papillomavirus DNA (p < 0.001) with the use of the polymerase chain reaction-in situ hybridization technique. Human papillomavirus 16 was detected in 18 of 26 specimens (69.2%), and 7 of 25 carcinomas (28%) were found to contain human papillomavirus 18. Dual infections were present in 5 of 21 (23.8%) specimens. Human papillomavirus DNA was more prevalent in men (75%) than women (57.1%). However, there was no difference in the mean age of patients with oral carcinoma (men, 67.8 years; women, 67.5 years) who had human papillomavirus and those who did not (67.2 years). Carcinomas associated with dual infections occurred at a lower mean age (59.4 years) than those associated with a single human papillomavirus type (p < 0.005). We conclude that the polymerase chain reaction-in situ hybridization technique enhances our ability to demonstrate human papillomavirus types highly associated with oral squamous cell carcinoma.
The purpose of this study was to determine the potential for human papillomavirus to be transmitted vertically.
We started a systematic study of children 0.3 to 11.6 years old born to mothers included in the cohort of 530 women prospectively followed up for genital human papillomavirus infections in Kuopio since 1981. So far 98 children have been examined. The examinations included medical history, clinical examination of the oral cavity and hand warts, and cytologic samples from the oral mucosa for detection of human papillomavirus deoxyribonucleic acid with polymerase chain reaction with subsequent Southern blot hybridization.
Human papillomavirus deoxyribonucleic acid was found in 31 of the 98 (31.6%) oral scrapings. with MY09 and MY11 human papillomavirus primers, 12 of the 98 were positive for human papillomavirus deoxyribonucleic acid in the electrophoresis gel and in subsequent hybridization. Nineteen of the positive samples were not visible in the gel but become positive when hybridized. At delivery, 5 mothers had genital human papillomavirus infection with the same virus type found in her child. In the additional 11 mothers genital human papillomavirus infection with the same virus type as in the child was diagnosed a few months before or after delivery. Mothers of the 25 children shown to be negative for oral human papillomavirus were also human papillomavirus deoxyribonucleic acid negative at delivery. Minor hyperplastic growths of the oral mucosa were found in 21 of the 98 children (21%). One child had a papilloma where human papillomavirus 16 deoxyribonucleic acid was detected, as was also found in her mother's genital area at delivery.
Our results support the concept that an infected mother can transmit human papillomavirus to her child.
The purpose of this study was to determine the potential of exposure of an infant to cervical human papillomavirus infection of the mother.
Cervical scrapes of the mothers and nasopharyngeal aspirate fluids of their infants were analyzed at the time of delivery. The study included 106 infants born by vaginal delivery or by cesarean section and their 105 mothers. Positive results were confirmed and typed by direct deoxyribonucleic acid sequencing or single-strand conformation polymorphism of the polymerase chain reaction product.
Both the mother's and her infant's samples were positive for the same type of human papillomavirus in 29 mother-infant pairs. Interestingly, five infants born by cesarean section were found to be human papillomavirus deoxyribonucleic acid positive for the same human papillomavirus type as their mother. The overall concordance between human papillomavirus types in the mother and her newborn was 69% (29/42). Regardless of match in types found in the mother's and her infant's sample, human papillomavirus deoxyribonucleic acid positivity was found in 39 of all the 106 infants (37%).
Our results indicate that the infant of the human papillomavirus-infected mother is exposed to infection even when the cervical infection of the mother is subclinical. The possibility of transplacental exposure has to be considered as well.
To describe the effect of delivery on respiratory status and outcome in the respiratory-compromised pregnant woman.
During 1990-1994, 10 patients requiring intubation for respiratory compromise who delivered during ventilatory support were identified by International Classification of Diseases, Ninth Revision codes. Charts were reviewed retrospectively for cardiorespiratory variables and outcome.
Pneumonia led to intubation in all but one case. The onset of labor was spontaneous in eight. Three were delivered by cesarean. Mechanical ventilation was used for a median (range) of 7 (2-22) days in surviving patients. Fraction of inspired oxygen requirements decreased an average of 28% by 24 hours after delivery. Positive end-expiratory pressure requirements remained unaltered. Surviving patients remained intubated for a median (range) of 2.6 (1-19) days postpartum. Three women died, all after vaginal delivery (days 4-14).
Delivery of respiratory-compromised gravidas resulted in a 28% reduction in fraction of inspired oxygen requirement within 24 hours after delivery. Although most patients were then able to be maintained below critical fraction of inspired oxygen requirement levels (under 0.6), dramatic improvement in overall respiratory function was not observed uniformly. Given the limited benefit of delivery on maternal oxygenation, along with the inherent risks of labor induction in this critically ill population, caution should be exercised in initiating the induction process electively.
To determine the transmission rate of human papillomavirus (HPV) in newborn infants of HPV-positive women and to assess the relationship between perinatal HPV transmission and mode of delivery.
Three hundred one pregnant women were selected: vaginal delivery (n = 160) or cesarean delivery (n = 141). We assessed the presence of the HPV types 16 and 18 DNA sequences in buccal and genital swabs of neonates born to HPV-positive mothers, using the polymerase chain reaction.
The overall frequency of HPV 16/18 infection among the pregnant women was 22.6% (68/301). At birth, the overall frequency of HPV transmission from HPV 16/18-positive mothers to newborns was 39.7% (27/68). A significantly higher rate of HPV 16/18 infection was found at birth when infants were delivered vaginally than when infants were delivered by cesarean (18/35 or 51.4% versus 9/33 or 27.3%, P = .042). However, there was no significant difference in the incidence of perinatal HPV infection between the HPV types 16 and 18 in either vaginal delivery group or in the cesarean delivery group (all P > .100). No significant difference was found between the buccal and genital sites (27/68 versus 21/68, P = .234) or between male and female infants overall (12/36 versus 15/32, P = .255).
The findings suggest that neonates are at higher risk for exposure to HPV after vaginal delivery than after cesarean delivery.
Benign tumors and lesions of the anogenital tract are caused by human papillomaviruses (HPVs). They are also major risk factors for cervical cancer. Introduction of the polymerase chain reaction (PCR) revealed that HPV infections are much more common among young asymptomatic women than it had been previously suspected. The side-specificity of genital HPVs led to the assumption that HPVs were primarily transmitted by sexual contact. However, since HPVs have been detected in virgins, infants/children and juvenile laryngeal papillomatosis was shown to be caused by these viruses, it became acknowledged that HPVs may be transmitted by other--non-sexual--routes as well. The evidence for sexual and different non-sexual routes of transmission of HPVs will be reviewed here.
The role of the male reproductive tract as a reservoir for human papillomavirus (HPV) infection is poorly understood. To analyze
the presence of HPV DNA, 27 samples, comprising postvasectomy semen samples and pre-and postejaculation urine samples, were
obtained from 18 men recalled for follow-up. HPV DNA was analyzed by nested polymerase chain reaction, confirmed with Southern
blot hybridization, cloned, and sequenced. Multiple HPV types were found in different DNA samples of the same men. Five (18.5%)
of 27 vas deferens samples contained HPV type 6, 11, or 16. Five (27.8%) of 18 seminal plasma samples (secretions without
semen cells) were HPV DNA positive. None of the men had both vas deferens and semen plasma samples HPV positive. Several HPV
types can be detected in the male reproductive tract at the same time. This is the first report to show HPV DNA in the vas
deferens.
