Are Mycoplasma pneumoniae coinfections frequent in COVID-19 patients? A systematic review.

Understanding the proportion of SARS-CoV-2 patients with Mycoplasmapneumoniae coinfection is crucial for treating patients suffering from coronavirus disease (COVID-19), help to ensure responsible use of antibiotics and minimize the negative consequences of overuse. In addition, this knowledge could have an impact on empirical antibiotic management guidelines for patients with COVID-19. This systematic review aimed to identify the prevalence of M. pneumoniae in patients with coronavirus disease 2019 (COVID-19). A bibliographic search of studies published in Spanish or English was conducted using the PubMed search engine. Fourteen articles from different continents (America, Asia and Europe) were included, involving a total of 5855 patients in these studies. The mean age of COVID-19 patients with M. pneumoniae was 48 years old (range 1-107), most of whom were male. The detection of laboratory-confirmed M. pneumoniae infection varied between 0 and 33.3%. Most of patients referred fever, cough, and dyspnea, and received empirical antibiotic treatment. Bacterial coinfection was not associated with increased ICU admission and mortality. The prevalence of coinfection showed extremely dissimilar figures according to the population studied and diagnostic criteria. However, it is important to develop Latin American studies, given the heterogeneity observed in the studies conducted in different countries. Standardized definitions should be developed in order to be able to assess the impact of coinfections in patients with a diagnosis of COVID-19.

Expression of HPV-16 E6 and E7 oncoproteins alters Chlamydia trachomatis developmental cycle and induces increased levels of immune regulatory molecules.

Introduction: Infection with Human Papillomavirus (HPV) is a recognized risk factor for Chlamydia trachomatis (CT) infection and vice versa. Coinfection of HPV and CT in women is a very common and usually asymptomatic finding that has been linked to increased risk of cervical cancer. It has been demonstrated that CT facilitates the entry of multiple high risk HPV genotypes, leading to damage of the mucosal barrier and interfering with immune responses and viral clearance, which ultimately favours viral persistence and malignant transformation. Although the facilitating effects elicited by CT infection on viral persistence have been reported, little is known about the consequences of HPV infection on CT development. Methods: Herein, we took advantage of a genetically modified human cervical cell line co-expressing HPV-16 major oncogenic proteins E6 and E7, as an experimental model allowing to investigate the possible effects that HPV infection would have on CT development. Results and discussion: Our results show that CT infection of HPV-16 E6E7 expressing cells induced an upregulation of the expression of E6E7 oncoproteins and host cell inhibitory molecules PD-L1, HVEM and CD160. Additionally, smaller chlamydial inclusions and reduced infectious progeny generation was observed in E6E7 cells. Ultrastructural analysis showed that expression of E6 and E7 did not alter total bacterial counts within inclusions but resulted in increased numbers of reticulate bodies (RB) and decreased production of infectious elementary bodies (EB). Our results indicate that during CT and HPV coinfection, E6 and E7 oncoproteins impair RB to EB transition and infectious progeny generation. On the other hand, higher expression of immune inhibitory molecules and HPV-16 E6E7 are cooperatively enhanced in CT-infected cells, which would favour both oncogenesis and immunosuppression. Our findings pose important implications for clinical management of patients with HPV and CT coinfection, suggesting that screening for the mutual infection could represent an opportunity to intervene and prevent severe reproductive health outcomes, such as cervical cancer and infertility.

Association between Human Papillomavirus and Chlamydia trachomatis genital infections in male partners of infertile couples.

The prevalence of HPV infection and its relationship with other sexually transmitted infections was analyzed in a cohort of 117 male partners of infertile couples from Cordoba, Argentina. Semen samples and urethral swabs were obtained and the infection with HPV, Chlamydia trachomatis, HSV1, HSV2, Mycoplasma hominis and Ureaplasma urealyticum was analyzed. A prevalence of HPV infection of 27.4% was found. Interestingly, infections by exclusively low risk HPV genotypes or high/intermediate risk HPV genotypes were present in 64.5% and 22.6% of cases, respectively. Low risk-HPV6 was the most frequently detected genotype. Remarkably, HPV and C. trachomatis infections were significantly associated to each other (OR: 11.55, 95% CI 1.14-117.06). No significant differences in sperm quality were found between HPV-positive and HPV-negative patients indicating that HPV male urogenital infection does not impair sperm quality. Our results show a high prevalence of HPV urogenital infection among male partners of infertile couples, and that HPV and C. trachomatis infections are reciprocal risk factors of their co-infection. Moreover, our results suggest that men constitute a reservoir for continued transmission of C. trachomatis and HPV to women highlighting the need for routine screening for these two pathogens in male partners of infertile couples.

[Prevalence of human papillomavirus and associated risk factors in women affiliated with state health insurance in Posadas, Misiones (Argentina)]. / Prevalencia del virus papiloma humano y factores de riesgo asociados en mujeres afiliadas al seguro de salud estatal en Posadas, Misiones (Argentina).

BACKGROUND: Human papilloma virus (HPV) is one of the most frequent sexually transmitted infections, especially among young people. AIMS: To describe the prevalence of genital HPV infections, to identify clinical-epidemiological factors associated with them and to determine the frequency of viral strains. METHODS: Endocervical samples were studied of 505 women between 15 and 49 years old, who attended the laboratory of the Institute of Social Security, residents of Posadas, Misiones, for the study of vaginal exudate, between January 2012 and June 2013. A 450-base pair fragment within the HPV L1 region was amplified. Genotype detection was performed through the study of the restriction fragment length polymorphism (RFLP). RESULTS: The prevalence of total HPV carriage was 30.7%, and of these 71.6% corresponded to high risk (mainly HPV 16 [35.1%], 58 [10.8%] and 31 [8.1%]). HPV detection was higher in women aged 15 to 24 years (OR: 1.48, 95% CI: 1.01-2.18) and with more sexual partners (OR: 1.81, 95% CI: 1, 02-3.22). There was no association with pregnancy, stability of the couple, contraceptive methods, age at onset of sexual intercourse, or smoking. CONCLUSIONS: The identification and typing of HPV in this study provides information regarding the high prevalence of HPV and the substantial proportion of cases with oncogenic genotypes among sexually active women in this region of Argentina.

Oral Human Papillomavirus: a multisite infection

BACKGROUND: The Human Papillomavirus (HPV) has different strategies for persist in the cells. This characteristic has led us to consider the presence of the virus in tissues of the oral cavity that had no clinical signs of infection. The aim of this study was to detect the presence of DNA-HPV at multiple sites of the oral cavity. MATERIAL AND METHODS: A case-control study was designed: Oral Squamous Carcinoma Group (OSCG), healthy n=72 and Control Group (CG), n=72, healthy volunteers paired by sex and age with OSCG. Four samples were taken from OSCG: saliva, biopsy, brush scraping of lesion and contralateral healthy side. In CG a saliva sample and a scratch of the posterior border of tongue were collected. HPV was detected by PCR using Bioneer Accuprep genomic DNA Extraction kit, and consensus primers MY09 and MY11. Chi square test was applied. RESULTS: 432 samples were obtained from 144 individuals. DNA-HPV was detected in 30 (42%) of OSCG subjects and 3 (4%) of CG. Two or more positive samples were obtained in 67% of the OSCG, 67% in saliva and 60% in biopsy; in CG 100% of the individuals were positive in the two samples. CONCLUSIONS: HPV is frequently present in oral cavity as a multifocal infection, even without the presence of clinical lesions

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Prevalencia del virus papiloma humano y factores de riesgo asociados en mujeres afiliadas al seguro de salud estatal en Posadas, Misiones (Argentina) / Prevalence of human papillomavirus and associated risk factors in women affiliated with state health insurance in Posadas, Misiones (Argentina)

Resumen Introducción: El virus papiloma humano (VPH) causa infecciones transmitidas sexualmente. Objetivos: Conocer la prevalencia de infecciones genitales por VPH, identificar factores clínico-epidemiológicos asociados a dicha prevalencia y determinar la frecuencia de los tipos virales. Material y Métodos: Se estudiaron muestras endo-cervicales de 505 mujeres entre 15 y 49 años, que concurrieron para estudio de exudado vaginal al laboratorio del Instituto de Previsión Social, residentes de Posadas, Misiones, entre enero de 2012 y junio de 2013. Se amplificó una sección de 450 pares de bases del genoma viral perteneciente al fragmento L1 del VPH. La detección del genotipo se realizó mediante el estudio del polimorfismo de la longitud de los fragmentos de restricción (RFLP). Resultados: La prevalencia de la portación de VPH total fue 30,7%, y de éstos 71,6% correspondió a los de alto riesgo (principalmente VPH 16 [35,1%], 58 [10,8%] y 31 [8,1%]). La detección del VPH fue mayor en mujeres de 15 a 24 años (OR: 1,48; IC 95% :1,01-2,18) y con más parejas sexuales (OR:1,81; IC 95%: 1,02-3,22). No hubo asociación con el embarazo, la estabilidad de la pareja, métodos anticonceptivos, edad de inicio de las relaciones sexuales ni tabaquismo. Conclusiones: Los resultados de identificación y tipificación de VPH en este estudio aportan información sobre una prevalencia elevada de VPH en mujeres sexualmente activas, así como porcentajes elevados de genotipos oncogénicos en esta región.

Abstract Background: Human papilloma virus (HPV) is one of the most frequent sexually transmitted infections, especially among young people. Aims: To describe the prevalence of genital HPV infections, to identify clinical-epidemiological factors associated with them and to determine the frequency of viral strains. Methods: Endocervical samples were studied of 505 women between 15 and 49 years old, who attended the laboratory of the Institute of Social Security, residents of Posadas, Misiones, for the study of vaginal exudate, between January 2012 and June 2013. A 450-base pair fragment within the HPV L1 region was amplified. Genotype detection was performed through the study of the restriction fragment length polymorphism (RFLP). Results: The prevalence of total HPV carriage was 30.7%, and of these 71.6% corresponded to high risk (mainly HPV 16 [35.1%], 58 [10.8%] and 31 [8.1%]). HPV detection was higher in women aged 15 to 24 years (OR: 1.48, 95% CI: 1.01-2.18) and with more sexual partners (OR: 1.81, 95% CI: 1, 02-3.22). There was no association with pregnancy, stability of the couple, contraceptive methods, age at onset of sexual intercourse, or smoking. Conclusions: The identification and typing of HPV in this study provides information regarding the high prevalence of HPV and the substantial proportion of cases with oncogenic genotypes among sexually active women in this region of Argentina.

Detection of human herpesvirus 6 (HHV-6) and human herpesvirus 7 (HHV-7) DNA in endocervical samples from a positive and negative HPV woman of Córdoba, Argentina.

AIMS: The purpose of the present study was to elucidate the presence of human herpesvirus 6A (HHV-6A), HHV-6B and HHV-7 in samples of the uterine cervix through detection of viral DNA. We analysed normal tissues, samples with low-grade squamous intraepithelial lesions (LSILs) and high-grade squamous intraepithelial lesions (HSILs). We correlated the presence of HHV-6 and HHV-7 with the finding of human papillomavirus (HPV) in mucosal samples. METHODS: Cervical samples were examined and grouped as follows: group 1 (n=29), normal cytology; group 2 (n=61), samples with LSIL; group 3 (n=35), samples with HSIL. Molecular biology examinations were performed in all samples to detect HHV-6, HHV-7 and HPV DNA and to typify HHV-6 species. RESULTS: Group 1: normal cytology and HPV (-): HHV-6: 6.8% (2/29), HHV-7: 79.3% (23/29); group 2: LSIL and HPV (-): HHV-6: 93.1% (27/29), HHV-7: 96.5% (28/29); LSIL and HPV (+): HHV-6: 0% (0/32), HHV-7: 90.6% (29/32); group 3: HSIL and HPV (-): HHV-6: 20% (2/10), HHV-7: 70% (7/10); HSIL HPV (+): HHV-6: 12% (3/25), HHV-7: 68% (17/25). HHV-6A DNA was not detected in any samples. CONCLUSIONS: (1) Both HHV-6 and HHV-7 infect the mucosal cells of the cervix with higher prevalence of HHV-7. (2) The higher prevalence of HHV-6 in LSIL HPV (-) samples compared with those with normal cytology indicates that it constitutes a possible risk factor for atypia production. (3) The presence of HHV-7 in all samples questions its role in the production of atypia. (4) The finding of HHV-6 and HHV-7 suggests that the cervical mucosa is a possible transmission pathway for these viruses.

Sexually transmitted infections in oral cavity lesions: Human papillomavirus, Chlamydia trachomatis, and Herpes simplex virus.

Objective: Provide evidence of HPV, C. trachomatis, and HSV infection in the oral cavity from patients with different types of stomatological lesions. Materials and Methods: Oral swabs samples were collected from a total of 318 patients. The infectious agents were analyzed using the PCR technique. HPV genotyping and HSV type were studied using the RFLP method. Results: We studied 137 benign lesions (B), 96 potentially malignant disorders (PMD) and 85 oral squamous cell carcinomas (OSCC). The prevalence of HPV was 34%. The most frequently genotypes detected were 6 low risk and 16 high risk. The prevalence of C. trachomatis was 16% and HSV 3%. Co-infections were detected mostly in benign lesions as following: HPV-C. trachomatis in 4%, C. trachomatis- HSV in 1.8% and HPV-HSV in 0.3%. Conclusion: This report is the first contribution to the identification and genotype characterization of HPV in a scenario little studied in our area, and it also contributes to improving our understanding on sexually transmitted infectious agents and their associations with the oral cavity. Besides, we detect the presence of C. trachomatis and HSV and co-infection with HPV in the oral cavity, which they should be taken into account for diagnostic and treatment purposes.

Prevalence, risk factors and molecular characterization of Chlamydia trachomatis in pregnant women from Córdoba, Argentina: A prospective study.

BACKGROUND: Chlamydia trachomatis causes the most prevalent bacterial Sexual Transmitted Infection. In pregnant women, untreated chlamydial infections are associated with abortions, premature rupture of membranes, postpartum endometritis, low birth weight and transmission to the newborn. In Córdoba, Argentina, there is little knowledge about the prevalence of Chlamydia trachomatis in women in their third trimester of pregnancy, so, the aim of this study was to evaluate Chlamydia trachomatis prevalence and genotypes present in Cordovan pregnant women with different age and socioeconomic status. METHODS AND FINDINGS: Design: prospective study. Settings: Women population from Cordoba city, Argentina. Population: Pregnant women having 35 to 37 weeks of gestation. Methods: Five hundred and nine cervical swabs were collected. Each sample was subjected to DNA extraction and PCR for Chlamydia trachomatis using primers NRO/NLO and CTP1/CTP2. Positives samples were sequenced to determine genotype. Main outcome measures: Demographic data of the patients were collected to detect a population at risk for this infection. RESULTS: A prevalence of 6.9% (35/509) for Chlamydia trachomatis infection was detected, with 32/295 and 3/214 from pregnant women with low or better economic resources respectively (p = 0,0001). Results showed a significantly increased rate of 11.6% (30/258) in women under 25 years compared with 2% (5/251) in patients over that age (p = 0,00003). Genotype E was the most prevalent. CONCLUSIONS: With these results, we can say that pregnant women under 25 years old and low economic resources are one of the populations in which the screening programs of Chlamydia trachomatis should focus.

Prevalencia y análisis filogenético de Chlamydia trachomatis en una población de mujeres de Posadas, Misiones / Prevalence and phylogenetic analysis of Chlamydia trachomatis in a population of women in Posadas, Misiones

Introducción. Chlamydia trachomatis es una de las bacterias más prevalentes en infecciones sexualmente transmisibles. En mujeres, la infección por C. trachomatis puede causar cervicitis y uretritis, aunque suele cursar en forma asintomática. El objetivo de este trabajo fue establecer la prevalencia de C. trachomatis y detectar los genotipos circulantes en mujeres que concurren al laboratorio del Instituto de Previsión Social. Material y métodos. Se analizaron 505 muestras endocervicales de mujeres sintomáticas y asintomáticas. Se determinó la presencia de C. trachomatis por PCR, mediante la amplificación de un fragmento del plásmido críptico. Las muestras positivas fueron genotipificadas mediante la amplificación parcial del gen ompA y se analizaron filogenéticamente. Resultados. Se detectaron 43 muestras positivas a la infección por C. trachomatis, obteniéndose una prevalencia de 8,5% (IC 95%: 6,4-11,3%). La prevalencia de C. trachomatis fue superior en las mujeres con sintomatología vaginal [11,3% (30/265) vs. 5,4% (13/240)] (p=0,018), así como en las mujeres menores de 26 años [11,5% (28/244) vs. 6,1% (15/246)] (p=0,021). A partir del análisis filogenético, se observó que el 62% de las muestras positivas para el gen ompA pertenecieron al genotipo E, 15% al genotipo J, 15% al genotipo D y 8% al F. Conclusiones. Este trabajo es el primer aporte sobre la epidemiología molecular de C. trachomatis en la provincia de Misiones, Argentina, que muestra la tasa de prevalencia de esta bacteria y ofrece información de genotipos circulantes (AU)

Background. Chlamydia trachomatis is the most prevalent bacteria causing sexually transmitted infections. In women, this infection can cause cervicitis and urethritis, although it’s usually asymptomatic. The aim of this study was to investigate the prevalence of C. trachomatis in women attending the lab Instituto de Previsión Social and detect the genotypes. Material and methods. Endocervical samples from 505 symptomatic and asymptomatic women were assayed. It was determined the presence of C. trachomatis by PCR through amplification of a fragment of the cryptic plasmid. Positive samples were genotyped by the partial amplification of the ompA gene and analyzed phylogenetically. Results. Forty-three positive samples were detected to infection with C. trachomatis, obtaining a prevalence of 8.5% (IC 95%: 6.4-11.3%). The prevalence of C. trachomatis was higher in women with vaginal symptoms [11.3% (30/265) vs. 5.4% (13/240)] (p = 0.018), as well as in women under 26 year-old [11.5% (28/244) vs. 6.2% (15/246)] (p = 0.021). Based on phylogenetic analysis, it was observed that 62% of the samples were genotype E, 15% genotype J, 15% genotype D, and 8% genotype F. Conclusions. This work is the first contribution on the molecular epidemiology of C. trachomatis in the Misiones province, Argentina, which shows the rate of prevalence of this bacterium and offers information on circulating genotypes (AU)

Knowledge of the General Community in Cordoba, Argentina, on Human Papilloma Virus Infection and its Prevention.

BACKGROUND: Most studies of human papilloma virus (HPV) are aimed at the natural history of the infection and its relation to cancer; however, there are few studies to assess knowledge of the general population. Our aim was analyze the degree of knowledge of Argentinians about HPV infection and its prevention. MATERIALS AND METHODS: We conducted a voluntary, anonymous and non-binding survey with 27 multiple-choice items, in twelve private and public establishments, selected to include a broad population in terms of education, age and gender. The survey consisted of three sections: individual characteristics of the volunteer, HPV infection basic knowledge, its prevention and the virus relationship with other cancers. RESULTS: One thousand two hundred ninety seven volunteers aged 18 to 80 participated. The total number of correct answers was 45.1%. The correct answers for relationship HPV and cervical cancer was 62.1%. Almost 55% did not know about types of HPV that the vaccines for protection. Statistical analysis showed that women, single people, workers, the better educated, those who have had a STDs or HPV and receiving information through medical or educational establishments had greater knowledge of the topic. Only 0.2% of participants answered all questions correctly. CONCLUSIONS: Knowledge plays an important role in health care and the deficiency found in our population could influence the success of the measures taken in the fight against cervical cancer. In this regard, we believe it would be appropriate, not only to emphasize early diagnosis and vaccine implementation, but also incorporate new communication strategies, facilitating reception of accurate and precise information by all strata of society.

Molecular characterization of Chlamydia pneumoniae in animals and humans from Argentina: Genetic characterization of Chlamydia pneumoniae.

In this study, genetic diversity of Chlamydia pneumoniae was investigated and the relationships between sequences amplified of different sources, clinical conditions and geographical regions of central Argentina were established. Samples amplified were similar to human C. pneumoniae patterns and show the high clonality of the population.

Eco-epidemiología de las Chlamydia psittaci, Chlamydia pneumoniae y Chlamydia pecorum: impacto en la salud pública / Eco Epidemiology of Chlamydia psittaci, Chlamydia pneumoniae and Chlamydia pecorum: impact on public healthpneumoniae by in vitro neutralization and microimmunofluorescence assays. Zentralbl Bakteriol 1996; 284(1):52-57.20. Phoon MC, Yee GW, Koh WP, Chow VT. Comparative Seroepidemiologic Analysis of Chlamydophila pneumoniae Infection using Microimmunofluorescence, Enzyme Immunoassay and Neutr

ntroducción: Las infecciones zoonóticas son una creciente amenaza para la salud mundial. Varias especies de Chlamydia y sus implicancias son poco conocidas. Objetivo: Profundizar el conocimiento eco-epidemiológico de Chla-mydia en Córdoba.Materiales y métodos: Se implementaron técnicas serológicas y mo-leculares para la detección de Chlamydia en 314 individuos sanos, 44 con nexo epidemiológico asociado a Psitacosis, 505 aves silvestres, 288 aves cautivas, 30 reptiles y 30 equinos. Resultados: En humanos se detectó C. pneumoniae, C. pecorum, C. psittaci, y co-infecciones asociadas a mayor cuantificación bac-teriana. La prevalencia de anticuerpos en indivi-duos sanos fue de 14,3 % y en pacientes 68,2 %. Se evidenció una respuesta inmune exacerbada en trabajadores en contacto con reptiles infectados con C. pneumoniae. En aves cautivas se identificó C. pneumoniae, C. psittaci, C. pecorum, C. galliná-cea y co-infecciones con mayor concentración de ADN. Las aves silvestres no excretaban Chlamydia. En equinos se halló C. pneumoniae, también en Su-ricata suricatta y Atelerix albiventris. El genotipo A se halló en humanos, reptiles, aves, mamíferos no humanos y B en equinos. Conclusiones: C. psittaci genotipo WC se detectó en aves y humanos; en menor frecuencia los genotipos E/B y A. Este hallazgo sugiere que los animales pueden representar una fuente subestimada de C. psittaci. El hallazgo de C. pneumoniae y C. pecorum en pacientes y en animales, plantea posibles ciclos zoonóticos y la necesidad de diagnóstico diferencial. Estos resultados avalaron el decreto de ley provincial de tenencia y comercialización de animales, promovido por la Secretaría de Am-biente de Córdoba

Introduction: Zoonotic infections are a growing threat to global health. Chlamydia and its implications are not well known.The aim of this study was to further the eco-epidemiological knowledge of Chlamydia in Cordoba.Materials and methods: Serological and molecular techniques was implemented for detection of Chlamydia in 314 healthy individuals, 44 individuals associated with Psittacosis, 505 wild birds, 288 captive birds, 30 reptiles and 30 equine.Results: In humans were detected C. pneumoniae, C. pecorum, C. psittaci and co-infections associated with increased bacterial quantification.The prevalence of antibodies in healthy individuals was 14.3% and 68.2% patients. Exacerbated immune response was detected in workers with contact infected with C. pneumoniae evidenced reptiles.In captive birds we detected C. pneumoniae, C. psittaci, C. pecorum, C. gallinácea and co-infections with the highest concentration of DNA. Wild birds did not excrete Chlamydia.In horses we found C. pneumoniae, also in Suricata suricatta and Atelerix albiventris. The genotype was found in humans, reptiles, birds, mammals and non-human equine B.Conclusions: C. psittaci WC genotype was detected in birds and humans; less frequently genotypes E/B and A. This finding suggests that animals can be a source of C. psittaci underestimated.The discovery of C. pneumoniae and C. pecorum in patients and animals raises potential zoonotic cycles and the need for differential diagnosis.These results endorsed the decree of provincial law to possess and marketing of animals, promoted by Secretaría de Ambiente de Córdoba

Mutation detection of E6 and LCR genes from HPV 16 associated with carcinogenesis.

Human papillomavirus (HPV) is responsible for one of the most frequent sexually transmitted infections. The first phylogenetic analysis was based on a LCR region fragment. Nowadays, 4 variants are known: African (Af-1, Af-2), Asian-American (AA) and European (E). However the existence of sub-lineages of the European variant havs been proposed, specific mutations in the E6 and LCR sequences being possibly related to persistent viral infections. The aim of this study was a phylogenetic study of HPV16 sequences of endocervical samples from Cordoba, in order to detect the circulating lineages and analyze the presence of mutations that could be correlated with malignant disease. The phylogenetic analysis determined that 86% of the samples belonged to the E variant, 7% to AF-1 and the remaining 7% to AF-2. The most frequent mutation in LCR sequences was G7521A, in 80% of the analyzed samples; it affects the binding site of a transcription factor that could contribute to carcinogenesis. In the E6 sequences, the most common mutation was T350G (L83V), detected in 67% of the samples, associated with increased risk of persistent infection. The high detection rate of the European lineage correlated with patterns of human migration. This study emphasizes the importance of recognizing circulating lineages, as well as the detection of mutations associated with high-grade neoplastic lesions that could be correlated to the development of carcinogenic lesions.