RESUMEN
The most widely used class of antivirals available for Influenza treatment are the neuraminidase inhibitors (NAI) Oseltamivir and Zanamivir. However, amino acid (AA) substitutions in the neuraminidase may cause reduced inhibition or high antiviral resistance. In Mexico, the current state of knowledge about NAI susceptibility is scarce, in this study we report the results of 14 years of Influenza surveillance by phenotypic and genotypic methods. A total of 255 isolates were assessed with the NAI assay, including Influenza A(H1N1)pdm09, A(H3N2) and Influenza B (IBV). Furthermore, 827 sequences contained in the GISAID platform were analyzed in search of relevant mutations.Overall, five isolates showed highly reduced inhibition or reduced inhibition to Oseltamivir, and two showed reduced inhibition to Zanamivir in the NAI assays. Additionally, five A(H1N1)pdm09 sequences from the GISAID possessed AA substitutions associated to reduced inhibition to Oseltamivir and none to Zanamivir. Oseltamivir resistant A(H1N1)pdm09 harbored the H275Y mutation. No genetic mutations were identified in Influenza A(H3N2) and IBV. Overall, these results show that in Mexico the rate of NAI resistance is low (0.6%), but it is essential to continue the Influenza surveillance in order to understand the drug susceptibility of circulating strains.
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Antivirales , Farmacorresistencia Viral , Virus de la Influenza B , Gripe Humana , Neuraminidasa , Oseltamivir , Zanamivir , Farmacorresistencia Viral/genética , Antivirales/farmacología , México/epidemiología , Humanos , Virus de la Influenza B/efectos de los fármacos , Virus de la Influenza B/genética , Gripe Humana/virología , Gripe Humana/tratamiento farmacológico , Gripe Humana/epidemiología , Oseltamivir/farmacología , Zanamivir/farmacología , Neuraminidasa/genética , Neuraminidasa/antagonistas & inhibidores , Subtipo H1N1 del Virus de la Influenza A/efectos de los fármacos , Subtipo H1N1 del Virus de la Influenza A/genética , Subtipo H1N1 del Virus de la Influenza A/aislamiento & purificación , Mutación , Subtipo H3N2 del Virus de la Influenza A/efectos de los fármacos , Subtipo H3N2 del Virus de la Influenza A/genética , Adulto , Virus de la Influenza A/efectos de los fármacos , Virus de la Influenza A/genética , Adolescente , Niño , Sustitución de Aminoácidos , Adulto Joven , Persona de Mediana Edad , Femenino , Preescolar , Genotipo , Masculino , Anciano , Pruebas de Sensibilidad Microbiana , Proteínas Virales/genéticaRESUMEN
High-Risk Human Papillomavirus (HR-HPV) types 16 and 18 are estimated to be responsible for 72.4% of all HPV-related cancers worldwide in both men and women, including cervical, anal, penile, vulval, vaginal and head and neck cancers [1]. Important efforts worldwide have devoted to the study of these genotypes, throughout epidemiology and basic science approaches. Of particular interest are the genes from the early region (E), coding non-structural proteins. Early genes E1 and E2 products are involved in replication and transcription regulation, while E6 and E7 proteins are recognised for their oncogenic potential. In this data report, we described a set of primers based on reference sequences from HPV16 and HPV18 designed to cover the early region of these oncogenic genotypes. The design was based on multiple sequences alignment to identify the less conserved regions along the open reading frames (ORFs) E6, E7, E1 and E2. The design allows a highly stringent real time PCR essay ranged from 123 to 598 bp overlapping products for HPV16 (12 products in total) and from 183 to 526 bp for HPV18 (11 products in total), both spanning the early genomic region. The high annealing temperatures (Ta) and regions selected for primer bind were intended for genotypic specificity, without compromising the qPCR amplification efficiency (≥ 90%). Evaluation of qPCR conditions for primer set was performed using DNA standards as controls, generated from the HPV16 and 18 genomes clones. This provides relevant information for further multiple quantitative real-time PCR analysis (qPCR), using the SYBR green chemistry, which is is more affordable than generating multiple fluorescently labeled probes.
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The incidence of anal intraepithelial neoplasias associated with HPV is rising worldwide. In the general population, this pathology is rare, but individuals living with HIV/AIDS are at a significantly higher risk. We aimed to study HPV infection and performed cytological screening to study the epidemiological and behavioral determinants in a group of men and women living with HIV from a region in Mexico with high HIV incidence. This was a cross-sectional study including adults living with HIV/AIDS performed in Merida (Mexico). We invited patients of public HIV/STD clinics and those affiliated with social organizations of people living with HIV to participate in the study. Participants responded to an instrument to assess their risky behaviors and clinical history. Swabs from the anal canal and cervix and anal cytology specimens were obtained by medical staff from women and by self-sampling from men. For the 200 participants, 169 men and 31 women, anal HPV PCR tests resulted in 59.8% positivity (62.6% of men and 45.2% of women), and 17 genotypes were identified. The most frequent high-risk (HR) types for the anal canal were: HPV33 (35.3%), HPV58 (20.6%), HPV66 (18.6%), HPV45 (17.6%), and HPV16 (14.7%). Multiple genotypes were found in over 80% of the participants. Receptive anal intercourse in the previous 12 months, inconsistent condom use, and detectable HIV titers (≥50 cc/mL) were associated with HPV infection (p < 0.05). Cytology (smears and liquid-based) identified that 34.6% of the participants had low-grade squamous intraepithelial lesions (LSILs), and 3.5% had high-grade squamous intraepithelial lesions (HSILs). Neither HPV nor lesions were associated with low CD4+ counts (<200 cells/mm3, p > 0.05). Of the women, 60% were infected in the cervix and 45% in the anal canal, with an agreement of at least one genotype in 90%. The HR-HPV types associated with HSILs were HPV66, 33, 52, 51, 45, 18, and 68.
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Several vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been approved for controlling the coronavirus disease 2019 (COVID-19) pandemic worldwide. Antibody response is essential to understand the immune response to different viral targets after vaccination with different vaccine platforms. Thus, the main aim of this study was to describe how vaccination with two distinct SARS-CoV-2 vaccine preparations elicit IgG antibody specific responses against two antigenically relevant SARS-CoV-2 viral proteins: the receptor-binding domain (RBD) and the full-length spike (S). To do so, SARS-CoV-2 protein specific in-house enzyme-linked immunosorbent assays (ELISAs) were standardized and tested against serum samples collected from 89 adults, recipients of either a single-dose of the Spike-encoding mRNA-based Pfizer/BioNTech (Pf-BNT) (70%, 62/89) or the Spike-encoding-Adenovirus-5-based CanSino Biologics Inc. (CSBIO) (30%, 27/89) in Merida, Mexico. Overall, we identified an IgG seroconversion rate of 88% (68/78) in all vaccinees after more than 25 days post-vaccination (dpv). Anti-RBD IgG-specific responses ranged from 90% (46/51) in the Pf-BNT vaccine at 25 dpv to 74% (20/27) in the CSBIO vaccine at 42 dpv. Compared to the S, the RBD IgG reactivity was significantly higher in both Pf-BNT (p < 0.004) and CSBIO (p < 0.003) vaccinees. Interestingly, in more than 50% of vaccine recipients, with no history of COVID-19 infection, antibodies against the nucleocapsid (N) protein were detected. Thus, participants were grouped either as naïve or pre-exposed vaccinees. Seroconversion rates after 25 and more dpv varies between 100% in Pf-BNT (22/22) and 75% (9/12) in CSBIO pre-exposed vaccinees, and 89% (26/29) and 73% (11/15) in Pf-BNT and CSBIO naïve vaccine recipients, respectively. In summary, observed seroconversion rates varied depending on the type of vaccine, previous infection with SARS-CoV-2, and the target viral antigen. Our results indicate that both vaccine preparations can induce detectable levels of IgG against the RBD or Spike in both naïve and SARS-CoV-2 pre-exposed vaccinees. Our study provides valuable and novel information about the serodiagnosis and the antibody response to vaccines in Mexico.
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OBJECTIVE: To analyze the presenceof human papillomavirus in prostate and its associationwith prostate cancer. METHODS: A case-control study was conducted.Tissue samples with benign hyperplasia and prostatecancer were collected. Risk factors related to prostatecancer and human papillomavirus were assessedby a medical interview. Prostate tissue was obtainedby transrectal biopsy or transurethral resection. Theidentification of viral genome was assessed by the amplificationof 450 pb., from L1 gene. Real time PCR wasused to identified HPV genotypes 16 and 18. For dataanalysis, the χ2 test, Student's T test or Mann-WhitneyU test and OR were computed. RESULTS: Thirty and 99 with benign prostatehyperplasia were included in a 1:3 ratio, with a meanage of 69.44±9.22 years. The global prevalence of humanpapillomavirus was 15.2% being similar in bothcases (15.6%) and controls (15.1%) with no significantdifference (p = 0.572). Forty percent of the infectionswere persistent. From all positive samples, only in the40% were identified some of the genotypes analyzed(16 and 18). The group of patients with Gleason scorede > 7 had a virus prevalence of 16%. CONCLUSIONS: The results show the presence ofthe human papillomavirus genome in prostate tissuewith and without neoplasia; no association was foundbetween infection and prostate cancer.
OBJETIVOS: Analizar la presencia delvirus de papiloma humano en próstata y su asociacióncon cáncer.MATERIAL Y MÉTODOS: Se realizó un estudiode casos y controles, para lo cual se colectaronmuestras de tejido con hiperplasia benigna y concáncer de próstata. Se realizó una historia clínicapara conocer la presencia de los factores de riesgoasociados al cáncer de próstata, así como los relacionadoscon el virus. El tejido prostático fue obtenidopor biopsia transrectal o resección transuretral.La identificación del genoma viral se realizó amplificandoun fragmento de 450 del gen L1 por mediode una PCR clásica. Para la identificación de los genotipos16 y 18, se utilizó PCR tiempo real. Para elanálisis de los datos se utilizó la prueba de χ2, pruebade T de Student o U de Mann-Whitney y cálculode OR. RESULTADOS: Se incluyeron 32 pacientes concáncer de próstata y 99 con hiperplasia benigna depróstata en una relación 1:3. La media de edad fuede 69.44±9.22 años. La prevalencia global del virusde papiloma humano fue de 15.2% siendo similar en los casos y entre casos (15.6%) y controles (15.1%),no existiendo diferencia significativa (p=0.572). El40% de las infecciones eran persistentes. Del totalde las muestras positivas, solamente en el 40% seencontró alguno de los dos genotipos analizados (16y 18). Los pacientes con un puntaje de Gleason > 7tuvieron una prevalencia del virus de 16%. CONCLUSIONES: Los resultados ponen de manifiestola presencia del genoma del virus del papilomahumano en próstata con y sin neoplasia, no se encontróasociación entre la infección y el cáncer de próstata.
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Alphapapillomavirus , Hiperplasia Prostática , Neoplasias de la Próstata , Alphapapillomavirus/genética , Estudios de Casos y Controles , Humanos , Masculino , Papillomaviridae/genéticaRESUMEN
As for 2020 only two complete genomes of Human papillomavirus type 13 (HPV13) are publicly available in GenBank database. In addition, reports of partial sequences of genetic regions are very limited. Therefore, genomic research that contributes to knowledge of viral components involved in HPV13 pathogenesis, and molecular mechanisms associated to multifocal epithelial hyperplasia (MEH) disease are urged. In the accompanying paper [1], we aimed to obtain the complete genome sequence of HPV13 associated to MEH disease, obtained from a Mayan boy living in Yucatan, Mexico. Coding sequences were annotated, and viral proteins traduced and deposited in GenBank with accession number MT068446. In this data report, we present the oligonucleotide list used to amplify the complete genome, a graphical abstract of process employed for the amplification of circular HPV13 genome, a representative figure of PCR products obtained for sequencing and multiple sequence alignments with the translated coding sequences of the existing genomes: X62843 is the first HPV13 genome reported [2]; it was generated from a clone obtained from a Turkish patient; DQ344807 was originally obtained from a patient in the Amazonian region [3]. The multiple sequence alignments show the main viral proteins (predicted). This provides relevant information for future molecular analysis and epidemiological studies because HPV13 is an understudied genotype associated to a neglected disease that appears more commonly in children. Additionally, the description of the methods can help in future sequencing of HPV genomes. We hope that our solutions will help researchers who do not have next-generation sequencing (NGS) platforms. A more comprehensive analysis of this data may be obtained from "Genomic characterization of Human papillomavirus type 13, associated to Multifocal Epithelial Hyperplasia, in a Mayan community" [1].
RESUMEN
Human papillomavirus type 13 (HPV13) is a low-risk HPV type associated with Multifocal Epithelial Hyperplasia (MEH). It is considered a rare pathology of oral mucosa, more prevalent in certain ethnical groups, such as the Maya from Yucatan in Mexico. As for 2020 only two complete genomes of HPV13 are publicly available in Genbank database (one from Turkey one from the Amazonian). We aimed to obtain the complete genome sequence of HPV13 associated to MEH, obtained from a community in the Mayan area from Mexico. A bank of oral swabs from children with MEH were used. To enrich the sample, a Rolling Cycle Amplification (RCA) method was performed followed by overlapping end-point PCR of 500â¯bp fragments, Sanger sequencing and assembly. Eight open reading frames (ORFs) were annotated (E1, E2, E4, E5, E6, E7, L1 and L2 genes). When compared with the other two previously reported genomes the identity at nucleotide level is high 98.9% and 99.6%, respectively. The phylogenetic tree shows that Yucatan HPV13 is more closely related to HPV13 obtained from the Amazonian. Most changes identified at amino acid level are substitutions derived from nucleotide variations or SNPs in coding regions. Amino-acid changes were observed in E2 and E1 proteins (nâ¯≥â¯8), and in L1, L2, E6 and E5 proteins (nâ¯≤â¯5). E7 protein from Yucatan has 100% identity with the reported from Amazonian and differs (94.1% identity) with the one from Turkey due to 3 substitutions and three missing amino acids. In conclusion, the genome from HPV13 (7831â¯bp, 49â¯nt missing) associated to MEH in the Mayan area from Yucatan was obtained from stored swabs; this is the first effort in Mexico, the second in Latin America, and the third of the world. More research that contributes to the knowledge of the determinants underlying this neglected pathology are urged.
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Alphapapillomavirus/genética , Hiperplasia Epitelial Focal/virología , Genoma Viral , Infecciones por Papillomavirus/complicaciones , Niño , Femenino , Humanos , Masculino , México , Infecciones por Papillomavirus/virología , Indio Americano o Nativo de AlaskaRESUMEN
Aloe vera is a crop of wide economic value of worldwide distribution, and a rich source of quinone components. Recently, antiviral aloe anthraquinones had been reported against human influenza virus. In the present work two anthraquinones, aloesaponarin-I (1) and aloesaponarin-II (2) were isolated from A. vera roots, and six derivatives were obtained by methylation (3), acetylation (4) and O-glycosyl (5-6) reactions starting from (1). Additionally, a new Tetra-O-acetyl-ß-d-glucopyranosyl derivative from 2 was also prepared. All compounds were evaluated against two strains of influenza virus AH1N1 by cytopathic effect reduction assay (CPE). The antiviral activity was determined by the ability of compounds to inhibit virus replication on Madin Darby Canine Kidney cells (MDCK). New derivatives 3-(2´,3´,4´,6´-Tetra-O-acetyl-ß-d-glucopyranosyl-aloesaponarin-I (5) and 3-(2´,3´,4´,6´-Tetra-O-acetyl-ß-d-glucopyranosyl- aloesaponarin-II (7) showed a cytopathic reduction effect against influenza strain A/Yucatán/2370/09 with IC50 of 30.77 and 13.70 µM, and against the virus A/Mexico/InDRE797/10 with IC50 of 62.28 and 19.47 µM, respectively. To assess the effect of derivatives 5 and 7 during one cycle of replication (0-10 h), a time-of-addition experiment was performed. As a result it was found that both compounds were most effective when added 6-10 h post-infection and significantly inhibited viral titre (> 70%) at the concentrations of 50 and 100 µM. Based on the structural analysis of the compounds, it was suggested that the Tetra-O-acetyl-ß-d-glucopyranosyl substituent at the C3 position of the anthraquinone might have an effect against the influenza AH1N1 virus.
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The 2012 and 2013 annual influenza epidemics in Mexico were characterized by presenting different seasonal patterns. In 2012 the A(H1N1)pdm09 virus caused a high incidence of influenza infections after a two-year period of low circulation; whereas the 2013 epidemic presented circulation of the A(H1N1)pdm09 virus throughout the year. We have characterized the molecular composition of the Hemagglutinin (HA) and Neuraminidase (NA) genes of the A(H1N1)pdm09 virus from both epidemic seasons, emphasizing the genetic characteristics of viruses isolated from Yucatan in Southern Mexico. The molecular analysis of viruses from the 2012 revealed that all viruses from Mexico were predominantly grouped in clade 7. Strikingly, the molecular characterization of viruses from 2013 revealed that viruses circulating in Yucatan were genetically different to viruses from other regions of Mexico. In fact, we identified the occurrence of two genetic variants containing relevant mutations at both the HA and NA surface antigens. There was a difference on the temporal circulation of each genetic variant, viruses containing the mutations HA-A141T / NA-N341S were detected in May, June and July; whereas viruses containing the mutations HA-S162I / NA-L206S circulated in August and September. We discuss the significance of these novel genetic changes.
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Variación Genética , Subtipo H1N1 del Virus de la Influenza A/aislamiento & purificación , Gripe Humana/epidemiología , Estaciones del Año , Genes Virales , Historia del Siglo XXI , Humanos , Subtipo H1N1 del Virus de la Influenza A/genética , Gripe Humana/virología , México/epidemiologíaRESUMEN
Resumen Introducción: La infección por VPH es la infección viral de transmisión sexual más frecuente, y se encuentra asociada a diversas neoplasias. Objetivo: Describir la epidemiología, historia natural y factores de riesgo asociados a la infección oral por VPH en adultos jóvenes asintomáticos. Métodos: Se realizó un estudio prospectivo de corte longitudinal, que incluyó sujetos sin patología oral, a los que se les tomó una muestra de la mucosa bucal. A todos los sujetos con resultados positivos se les realizó un nuevo muestreo seis meses después. Se identificó la presencia del virus por RPC; los datos demográficos y de conducta sexual fueron obtenidos con una encuesta que respondieron sin intervención del investigador. Resultados: Se recolectaron 102 muestras de sujetos de 18-26 años de edad, 60 (58,8%) correspondieron al sexo masculino. La prevalencia del virus fue de 6,9%; todos los sujetos positivos tenían vida sexual. Las relaciones sexuales entre personas del mismo sexo fue la única variable asociada a la presencia del virus (p < 0,05). A los seis meses, todos los sujetos habían eliminado al virus. Conclusión: La infección oral por VPH es transitoria y está asociada a relaciones sexuales entre personas del mismo sexo, principalmente mujeres que tienen sexo con mujeres.
Background: HPV infection is the most common sexually transmitted viral infection, and is associated with several neoplasms. Aim: To describe the epidemiology, natural history and risk factors associated with oral HPV infection in asymptomatic young adults. Methods: A prospective and longitudinal study was conducted, including subjects without oral pathology, who were sampled from the oral mucosa. All subjects with positive results were re-sampled 6 months later. The presence of HPV was identified by PCR. Demographic and sexual behavior data were obtained with a survey that was responded without the intervention of the researcher. Results: 102 samples were collected from subject of 18-26 years old, 60 (58.8%) were male. The prevalence of the virus was 6.9%; all positive subjects had active sexual life. Same-gender relationships were the only variable associated with the presence of the virus (p < 0.05). At six months all subjects had eliminated the virus. Conclusion: Oral HPV infection is transient and is associated to same-gender relationships, mainly women who have sex with women.
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Humanos , Masculino , Femenino , Adulto , Adulto Joven , Enfermedades Virales de Transmisión Sexual/transmisión , Enfermedades Virales de Transmisión Sexual/epidemiología , Infecciones por Papillomavirus/transmisión , Infecciones por Papillomavirus/epidemiología , Boca/virología , Papillomaviridae/aislamiento & purificación , Conducta Sexual , Factores Sexuales , Reacción en Cadena de la Polimerasa , Prevalencia , Estudios Prospectivos , Factores de Riesgo , Conductas de Riesgo para la Salud , Genotipo , México/epidemiologíaRESUMEN
INTRODUCTION: While vaccination may be relatively straightforward for regions with a well-defined winter season, the situation is quite different for tropical regions. Influenza activity in tropical regions might be out of phase with the dynamics predicted for their hemispheric group thereby impacting the effectiveness of the immunization campaign. OBJECTIVE: To investigate how the climatic diversity of Mexico hinders its existing influenza immunization strategy and to suggest that the hemispheric vaccine recommendations be tailored to the regional level in order to optimize vaccine effectiveness. METHODS: We studied the seasonality of influenza throughoutMexico by modeling virological and mortality data.De-trended time series of each Mexican state were analyzed by Fourier decomposition to describe the amplitude and timing of annual influenza epidemic cycles and to compare with each the timing of the WHO's Northern and Southern Hemispheric vaccination schedule. FINDINGS: The timings of the primary (major) peaks of both virological and mortality data for most Mexican states are well aligned with the Northern Hemisphere winter (December-February) and vaccine schedule. However, influenza peaks in September in the three states of the Yucatan Peninsula. Influenza-related mortality also peaks in September in Quintana Roo and Yucatan whereas it peaks in May in Campeche. As the current timing of vaccination in Mexico is between October and November, more than half of the annual influenza cases have already occurred in the Yucatan Peninsula states by the time the Northern Hemispheric vaccine is delivered and administered. CONCLUSION: The current Northern Hemispheric influenza calendar adopted for Mexico is not optimal for the Yucatan Peninsula states thereby likely reducing the effectiveness of the immunization of the population. We recommend that Mexico tailor its immunization strategy to better reflect its climatologic and epidemiological diversity and adopt the WHO Southern Hemisphere influenza vaccine and schedule for the Yucatan Peninsula.
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Esquemas de Inmunización , Vacunas contra la Influenza/administración & dosificación , Gripe Humana/epidemiología , Gripe Humana/prevención & control , Estaciones del Año , Clima , Humanos , Vacunas contra la Influenza/efectos adversos , México/epidemiología , Vigilancia de la Población , Potencia de la Vacuna , Organización Mundial de la SaludRESUMEN
BACKGROUND/AIMS: The study aimed to describe human papillomavirus (HPV) 58 genetic variability in E6 and E7 oncogenes from women in southeast Mexico and their phylogenetic relationships with the sequences from other geographical regions. METHODS: The E6-E7 region was amplified by nested PCR, and sequenced for identification of polymorphisms, phylogenetic trees construction, and haplotype and fixation tests. RESULTS: HPV58 positive samples were obtained from a repository, 54 were amplified, 47 sequences for the E6 gene, and 51 sequences for the E7 gene were obtained. Fifteen new E6 mutations were found; the most frequent were G279T (G57V; 29.78%), T249G (F47C; 34.04%), and A270G (Y54C; 34.04%), and previously reported c307t (63.82%). For E7, 17 known mutations were found, the most frequent were C632T (T20I), 35.30%, G760A (G63S), 35.30%, and t744g 74.50%. No significant association with the severity of the lesions was found. The polytomy in the E6 tree did not allow proposing phylogenetic relationship, and E7 tree presented defined branches. All sequences were presumably A lineage, most closely related to A1 and/or A3 sublineage. HPV58 variants are not specific for a geographical area. Population and fixation analyses suggest a possible Asian origin of HPV58 from Yucatan. The most frequent E7 haplotype in Yucatan groups with other populations of the world. CONCLUSION: The genetic variability of HPV58 from Mexico was described for the first time. E7 was more conserved than E6. New mutants present exclusively in Yucatan were identified.
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BACKGROUND: HPV infection is the most common sexually transmitted viral infection, and is associated with several neoplasms. AIM: To describe the epidemiology, natural history and risk factors associated with oral HPV infection in asymptomatic young adults. METHODS: A prospective and longitudinal study was conducted, including subjects without oral pathology, who were sampled from the oral mucosa. All subjects with positive results were re-sampled 6 months later. The presence of HPV was identified by PCR. Demographic and sexual behavior data were obtained with a survey that was responded without the intervention of the researcher. RESULTS: 102 samples were collected from subject of 18-26 years old, 60 (58.8%) were male. The prevalence of the virus was 6.9%; all positive subjects had active sexual life. Same-gender relationships were the only variable associated with the presence of the virus (p < 0.05). At six months all subjects had eliminated the virus. CONCLUSION: Oral HPV infection is transient and is associated to same-gender relationships, mainly women who have sex with women.