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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.
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INTRODUCTION: The prevalence of the different genotypes of human papillomavirus (HPV) varies depending on lesion severity and geographic region. OBJECTIVE: To identify multiple HPV infections in low- and high-grade cervical lesions in a group of women from the Mexican Bajío region referred with inconclusive cytology. METHODS: Pilot study of women referred from primary care units of Guanajuato, Mexico, with cytology suggestive of cervical lesion. Cervical smears were subjected to DNA extraction and HPV genotyping using microarrays. RESULTS: 100 consecutive cases were collected and 90 were analyzed; HPV positivity was observed in 26% of healthy women, and 62% had some degree of cervical lesion. The most common HPV genotypes were 59, 31, 16 and 51. Multiple infections were found in most samples. CONCLUSIONS: HPV heterogeneity was identified in the samples of the study population in contrast to worldwide reports; furthermore, multiple infections are common in precursor lesions and decrease in high-grade lesions. These data could have an impact on current HPV vaccination programs.
INTRODUCCIÓN: La prevalencia de los diferentes genotipos de virus del papiloma humano (VPH) varía dependiendo de la severidad de la lesión y región geográfica. OBJETIVO: Identificar infecciones múltiples de VPH en lesiones cervicales de bajo y alto grado en un grupo de mujeres del Bajío mexicano referidas con citología no concluyente. MÉTODOS: Estudio piloto de mujeres referidas de unidades del primer nivel de atención de Guanajuato, México, por citología sugerente de lesión cervical. Los raspados cervicales fueron sujetos a extracción de ADN y genotipificación del VPH mediante microarreglos. RESULTADOS: Se colectaron 100 casos consecutivos y fueron analizados 90; se observó 26 % de positividad a VPH en mujeres sanas y 62 % presentó algún grado de lesión. Los genotipos de VPH más frecuentes fueron 59, 31, 16 y 51. En la mayoría de las muestras se encontró infección múltiple. CONCLUSIONES: Se identificó heterogeneidad de VPH en las muestras de la población estudiada en contraste con los reportes internacionales; además, son comunes las infecciones múltiples en lesiones precursoras y disminuyen en las lesiones de alto grado. Estos datos podrían influir en los actuales programas de vacunación anti-VPH.
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Infecções por Papillomavirus , Humanos , Feminino , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Projetos Piloto , Papillomaviridae/genética , Genótipo , Prevalência , DNARESUMO
Resumen Introducción: La prevalencia de los diferentes genotipos de virus del papiloma humano (VPH) varía dependiendo de la severidad de la lesión y región geográfica. Objetivo: Identificar infecciones múltiples de VPH en lesiones cervicales de bajo y alto grado en un grupo de mujeres del Bajío mexicano referidas con citología no concluyente. Métodos: Estudio piloto de mujeres referidas de unidades del primer nivel de atención de Guanajuato, México, por citología sugerente de lesión cervical. Los raspados cervicales fueron sujetos a extracción de ADN y genotipificación del VPH mediante microarreglos. Resultados: Se colectaron 100 casos consecutivos y fueron analizados 90; se observó 26 % de positividad a VPH en mujeres sanas y 62 % presentó algún grado de lesión. Los genotipos de VPH más frecuentes fueron 59, 31, 16 y 51. En la mayoría de las muestras se encontró infección múltiple. Conclusiones: Se identificó heterogeneidad de VPH en las muestras de la población estudiada en contraste con los reportes internacionales; además, son comunes las infecciones múltiples en lesiones precursoras y disminuyen en las lesiones de alto grado. Estos datos podrían influir en los actuales programas de vacunación anti-VPH.
Abstract Introduction: The prevalence of the different genotypes of human papillomavirus (HPV) varies depending on lesion severity and geographic region Objective: To identify multiple HPV infections in low- and high-grade cervical lesions in a group of women from the Mexican Bajío region referred with inconclusive cytology. Methods: Pilot study of women referred from primary care units of Guanajuato, Mexico, with cytology suggestive of cervical lesion. Cervical smears were subjected to DNA extraction and HPV genotyping using microarrays. Results: 100 consecutive cases were collected and 90 were analyzed; HPV positivity was observed in 26% of healthy women, 62% had some degree of cervical lesion. The most common HPV genotypes were 59, 31, 16 and 51. Multiple infections were found in most samples. Conclusions: HPV heterogeneity was identified in the samples of the study population in contrast to worldwide reports; furthermore, multiple infections are common in precursor lesions and decrease in high-grade lesions. These data could have an impact on current HPV vaccination programs.
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Background: Human papillomavirus (HPV) subtypes 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68 have been implicated in the development of cervical cancer (CC). These 13 high risk HPV types have been shown to be present in up to 99.7% of CC samples. In Mexico, this cancer is the leading cause of death from malignancy among women. The aim of this study was to determine the prevalence of different HPV genotypes and investigate epidemiological aspects associated with HPV infection in women from Cozumel. Material and methods: We performed an epidemiological, prospective and cross sectional study with 1,187 who accepted participation in a campaign of screening for CC, during the period 2014 to 2015. Data on epidemiological and socio-economic variables were obtained. Cervical cells were collected for detection of HPV DNA and typing of HPV-positive samples by Multiplex PCR, using a commercial kit for 16 viral genotypes. Results: The overall prevalence of HPV in women from Cozumel was 15.8 % (188/1,187), either single (13.6%) or multiple (2.19 %). The most common HPV types , in descending order of frequency, were 58 (24.5 %), 59 (13.3 %), 39 (12.2 %) and 66 (9.6 %). The most frequent high risk types were HPV-58 and -59 and of low risk HPV types the most common was HPV-6. Number of sexual partners (OR=4.78; 95% CI= 2.73-8.37; P=<0.0001) and age of first coitus (OR=0.51; 95% CI=0.32-0.81; P=<0.0011) were significantly associated with HPV infection. Conclusions: Our data indicate that the overall incidence of high risk HPV infection in Cozumel is low as compared to other studies worldwide, with a different profile of subtypes. However, as expected, risky sexual behavior was found associated with positive cases of HPV. These results highlight the need for establish strategies to prevent HPV acquisition and evaluate the impact of a vaccine application in the Cozumel population.
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Papillomaviridae/genética , Infecções por Papillomavirus/virologia , Adulto , Idoso , Colo do Útero/patologia , Colo do Útero/virologia , Estudos Transversais , DNA Viral/genética , Estudos Epidemiológicos , Feminino , Genótipo , Humanos , Incidência , México , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Assunção de Riscos , Comportamento Sexual , Parceiros Sexuais , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Adulto JovemRESUMO
BACKGROUND: Curaçao is a Dutch-Caribbean Island located in a high-risk area for cervical cancer.Prior to introduction of a prophylactic human papillomavirus (HPV) vaccine, knowledge of the prevalence of high-risk HPV vaccine genotypes (HPV16, 18, 31, 33, 45, 52 and 58) in cervical (pre)cancer is required. OBJECTIVE: To investigate the prevalence of HPV genotypes in invasive cervical cancers (ICC) and cervical intraepithelial neoplasia (CIN) grade 1, 2 and 3 in Curaçao. METHODS: Paraffin-embedded blocks of 104 cervical cancers (89 squamous, 15 adenocarcinoma), 41 CIN3, 39 CIN2 and 40 CIN1 lesions were analysed for the presence of HPV. Sections were stained by H&E for histopathological evaluation, and DNA was extracted using proteinase K. HPV genotypes were detected using Short PCR Fragment (SPF10) PCR DNA enzyme immunoassay and a Line Probe Assay (LiPA25) . RESULTS: HPV was found in 92 (88.5%) ICC; 87 (94.6%) had a single HPV infection and 86 (93.5%) were high-risk human papillomavirus (hrHPV)-type positive.The three most common HPV types in ICC were 16 (38.5%), 18 (13.5%) and 45 (6.7%), covering 58.7%.HrHPV vaccine genotypes 16, 18, 31, 35, 45, 52 and 58 were responsible for 73.1% of ICC. For precancerous lesions, the HPV attribution was 85.4% for CIN3, 66.7% for CIN2% and 42.5% for CIN1. CONCLUSIONS: Our study, the largest in the Caribbean region in (pre)cancer, shows that the prevalence of HPV-type 16 and 18 in cervical cancer is lower compared with the world population but no differences in prevalence of these two HPV types are seen in precancerous lesions.When considering HPV vaccination in Curaçao, the relatively high contribution of non-HPV 16/18 genotypes in ICC should be taken into account.
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Adenocarcinoma/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Infecções por Papillomavirus/epidemiologia , Displasia do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Adenocarcinoma/prevenção & controle , Adenocarcinoma/virologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Alphapapillomavirus/genética , Carcinoma de Células Escamosas/prevenção & controle , Carcinoma de Células Escamosas/virologia , Curaçao/epidemiologia , Detecção Precoce de Câncer , Feminino , Genótipo , Humanos , Programas de Rastreamento , Pessoa de Meia-Idade , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus , Prevalência , Estudos Retrospectivos , Fatores de Risco , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/virologia , Adulto Jovem , Displasia do Colo do Útero/prevenção & controle , Displasia do Colo do Útero/virologiaRESUMO
Objetivo: Examinar la prevalencia de la infección por virus papiloma humano en pacientes con citologías de cuello uterino negativas, en un programa de pesquisa de cáncer de cuello de la Misión Barrio Adentro. Métodos: Se analizaron 3883 muestras citológicas convencionales de cuello uterino según el sistema Bethesda 2001, de las cuales 3651 (94,0 %) eran citologías normales. Se usó PCR/RFLP para la detección y tipificación de virus de papiloma humano. Resultados: La edad promedio de las pacientes fue de 34,8 ± 12,20 años (rango: 13 a 89). La prevalencia general de la infección fue de 28,5 % (1038/3651). En 31,9 % se detectó virus de papiloma humano de alto riesgo oncogénico y en 21,2 % de bajo riesgo oncogénico. El virus de papiloma humano 6 (57,7 %) fue el genotipo de mayor prevalencia, seguido de secuencias desconocidas del virus (45,4 %). El virus de papiloma humano 16 fue el más comúnmente encontrado (28,09 %) entre los de alto riesgo, seguido del 18 (17,5 %) y el 31 (14,2 %) (p<0,000). También se detectó 33 (4,8 %), 52 (4,2 %), 53 (3,6 %) y 58 (3,1 %). A medida que aumentó la edad, disminuyó la positividad para la infección por el virus de papiloma humano (p<0,000) y la mayor prevalencia viral se presentó en menores de 25 años (35,1 %). Conclusiones: La prevalencia de virus de papiloma humano en pacientes con citologías negativas es elevada y heterogénea en este medio, observándose una mezcla de virus de alto y bajo riesgo.
Objective: To examine the prevalence of human papillomavirus infection in patients with negative cervical cytology in a cervical cancer screening program of the Barrio Adentro Mission in Venezuela. Methods: A total of 3,883 conventional cervical cytology samples were analyzed according to the Bethesda 2001 system, of which 3651 (94.0%) were reported normal cytology. PCR / RFLP were used for the detection and typing of human papilloma virus. Results: The mean age of the patients was 34.8 ± 12.20 years (range: 13 to 89). The overall prevalence of infection was 28.5% (1038/3651). In 31.9% of cases high oncogenic risk human papillomavirus were detected and 21.2% of HPV low oncogenic risk. Human papillomavirus 6 (57.7%) was the most prevalent genotype, followed by unknown virus sequences (45.4%). Human papillomavirus 16 was the most commonly found (28.09%) among high risk, followed by 18 (17.5%) and 31 (14.2%) (p <0.000). We also detected 33 (4.8%), 52 (4.2%), 53 (3.6%) and 58 (3.1%). As age increased, the positivity for human papillomavirus (p <0.000) decreased, and the highest viral prevalence occurred in womens under 25 (35.1%). Conclusions: The prevalence of human papilloma virus in patients with negative cytology is high and heterogeneous in this medium, with a mixture of high and low risk viruses.
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OBJECTIVE: To determine the frequency of human papillomavirus (HPV) types and to assess bacterial vaginosis (BV) possible associations with cervical infections in indigenous Paraguayan women of the Department of Presidente Hayes. METHODS: This study included 181 sexually active women without cervical lesions. HPV typing was performed by polymerase chain reaction with primers PGMY 09/11 followed by reverse line hybridization. BV was diagnosed by the Nugent criteria using the results from a Gram stain smear. RESULTS: Sixteen percent of women were positive for at least one high risk HPV type (HR-HPV). The most frequent genotypes were HPV 16 (4.4%), followed by HPV 58 (3.3%), HPV 45 (3.3%), HPV 53 (2.8%) and HPV 11 (2.8%). A significant association between HR-HPV and BV was observed (p=0.01). In addition, women with BV had a higher frequency of Chlamydia trachomatis (p=0.0007), Trichomonas vaginalis (p=0.00009), Mycoplasma hominis (p=0.001). CONCLUSIONS: A large variety of HPV genotypes was detected and showed a slightly different pattern from previous studies on urban women in Paraguay, with the predominance of HR-HPV. Furthermore, the information of co-infections involved in BV could be useful for the improvement of national prevention programs, as well as for laboratory surveillance of these genital infections.