miRNAs signature as potential biomarkers for cervical precancerous lesions in human papillomavirus positive women.

Biomarkers to identify women at risk of cervical cancer among those with high-risk HPV infection (hrHPV+) are needed. Deregulated expression of microRNAs (miRNAs) contributes to hrHPV-induced cervical carcinogenesis. We aimed at identifying miRNAs with the capacity to distinguish high (CIN2+) and low (≤ CIN1) grade cervical lesions. We sequenced miRNA libraries from Formalin-Fixed Paraffin-Embedded (FFPE) tissues from women with CIN2+ (n = 10) and age-matched women with ≤ CIN1 (n = 10), randomly and retrospectively selected from a trial that followed women for 24 months after a hrHPV+ test at the screening visit. Five miRNAs differentially expressed were validated by RT-qPCR in an independent set of FFPE tissues with a reviewed diagnosis of CIN2+ (n = 105) and ≤ CIN1 (n = 105). The Ingenuity Pathway Analysis (IPA) was conducted to identify mRNAs inversely correlated with the top 25 differentially expressed miRNAs. Inverse correlations with 401 unique mRNA targets were identified for fourteen of the top 25 differentially expressed miRNAs. Eleven of these miRNAs targeted 26 proteins of pathways deregulated by HPV E6 and E7 oncoproteins and two of them, miR-143-5p and miR-29a-3p, predicted CIN2+ and CIN3+ in the independent validation by RT-qPCR of FFPE tissues from hrHPV-positive women.

Comparison of immediate colposcopy, repeat conventional cytology and hrHPV testing for the clinical management of ASC-US cytology in routine health services of Medellin, Colombia: The ASCUS-COL Trial.

In the context of opportunistic cervical cancer screening settings of low-and-middle-income countries, little is known about the benefits of high-risk human papillomavirus (hrHPV) testing on high-grade cervical abnormality detection among women with atypical squamous cells of undetermined significance (ASC-US) cytology in routine clinical practice. We compared the effectiveness of immediate colposcopy (IC), conventional cytology at 6 and 12 months (colposcopy if ≥ASC-US) (RC), and hrHPV testing (colposcopy if hrHPV-positive) (HPV) to detect cervical intraepithelial neoplasia grade 2 or more severe diagnoses (CIN2+) among women aged 20-69 years with ASC-US in routine care. Participants (n=2,661) were evenly randomized into three arms (n=882 IC, n=890 RC, n=889 HPV) to receive services by routine healthcare providers and invited to an exit visit 24 months after recruitment. Histopathology was blindly reviewed by a quality-control external panel (QC). The primary endpoint was the first QC-diagnosed CIN2+ or CIN3+ detected during three periods: enrolment (≤6 months for IC and HPV, ≤12 months for RC), follow-up (between enrolment and exit visit), and exit visit. The trial is completed. Colposcopy was done on 88%, 42%, and 52% of participants in IC, RC, and HPV. Overall, 212 CIN2+ and 52 CIN3+ cases were diagnosed. No differences were observed for CIN2+ detection (p=0.821). However, compared to IC, only HPV significantly reduced CIN3+ cases that providers were unable to detect during the 2-year routine follow-up (relative proportion 0.35, 95% CI 0.09-0.87). In this context, hrHPV testing was the most effective and efficient management strategy for women with ASC-US cytology.

Prevalence of Chlamydia trachomatis in an asymptomatic female population attending cervical cytology services of three healthcare centers in Medellín, Colombia / Prevalencia de Chlamydia trachomatis en la población femenina asintomática atendida en los servicios de citología cervical de tres instituciones prestadoras de servicios de salud en Medellín, Colombia.

Introduction: The sexually transmitted infection caused by Chlamydia trachomatis is the most common of bacterial etiology in the world. Although it can be asymptomatic in most cases, it can produce several reproductive health problems in women such as cervicitis, endometritis, and salpingitis. Despite its importance, the epidemiological data on this infection is insufficient in Medellín. Objective: To determine the prevalence of C. trachomatis in women from Medellín, identify possible risk factors, and evaluate its relationship with the human papillomavirus infection (HPV). Materials and methods: We conducted a multicenter cross-sectional study to detect C. trachomatis infection in 1,282 women using PCR and the LightMix 480 HT CT/NG™ commercial kit (Roche, Basel, Switzerland). Results: The total prevalence of C. trachomatis infection was 4.1% (95% CI: 2.9-5.3). We found an association between the presence of the infection and age, cigarette consumption, and the use of hormonalcontraceptives. Conclusion: The prevalence of the infection is similar to that reported in other parts of the world with young women being the most affected population. No relation was found with the presence of HPV.

Introducción. La infección de transmisión sexual causada por Chlamydia trachomatis es la más frecuente de etiología bacteriana en el mundo. Aunque puede ser asintomática en la mayoría de los casos, C. trachomatis puede generar diversos problemas de salud reproductiva en mujeres, como cervicitis, endometritis y salpingitis. A pesar de su importancia, en Medellín no se cuenta con suficientes datos epidemiológicos sobre esta infección. Objetivo. Determinar la prevalencia de C. trachomatis en mujeres de Medellín, determinar los posibles factores de riesgo y evaluar la relación con la infección por el virus de papiloma humano (HPV). Materiales y métodos. Se hizo un estudio transversal multicéntrico para detectar la infección por C. trachomatis en 1.282 mujeres mediante reacción en cadena de la polimerasa (PCR) convencional y el estuche comercial LightMix 480 HT CT/NG™ (Roche, Basilea, Suiza). Resultados. La prevalencia total de la infección por C. trachomatis fue de 4,1 % (IC95% 2,9-5,3). Se encontró una relación significativa de la infección con la edad, el consumo de cigarrillo y el uso de anticonceptivos hormonales. Conclusión. La prevalencia de la infección es similar a la reportada en otros lugares del país y del mundo, siendo las mujeres más jóvenes las más afectadas. En cuanto a la presentación del HPV, no se encontró ningún tipo de relación con C. trachomatis.

Prevalencia de Chlamydia trachomatis en la población femenina asintomática atendida en los servicios de citología cervical de tres instituciones prestadoras de servicios de salud en Medellín, Colombia / Prevalence of Chlamydia trachomatis in an asymptomatic female population attending cervical cytology services of three healthcare centers in Medellín, Colombia

Introduction:The sexually transmitted infection caused by Chlamydia trachomatis is the most common of bacterial etiology in the world. Although it can be asymptomatic in most cases, it can produce several reproductive health problems in women such as cervicitis, endometritis, and salpingitis. Despite its importance, the epidemiological data on this infection is insufficient in Medellín. Objective: To determine the prevalence of C. trachomatis in women from Medellín, identify possible risk factors, and evaluate its relationship with the human papillomavirus infection (HPV). Materials and methods: We conducted a multicenter cross-sectional study to detect C. trachomatis infection in 1,282 women using PCR and the LightMix 480 HT CT/NG™ commercial kit (Roche, Basel, Switzerland). Results: The total prevalence of C. trachomatis infection was 4.1% (95% CI: 2.9-5.3). We found an association between the presence of the infection and age, cigarette consumption, and the use of hormonal contraceptives. Conclusion: The prevalence of the infection is similar to that reported in other parts of the world with young women being the most affected population. No relation was found with the presence of HPV.

Introducción. La infección de transmisión sexual causada por Chlamydia trachomatises la más frecuente de etiología bacteriana en el mundo. Aunque puede ser asintomática en la mayoría de los casos, C. trachomatis puede generar diversos problemas de salud reproductiva en mujeres, como cervicitis, endometritis y salpingitis. A pesar de su importancia, en Medellín no se cuenta con suficientes datos epidemiológicos sobre esta infección. Objetivo. Determinar la prevalencia de C. trachomatis en mujeres de Medellín, determinar los posibles factores de riesgo y evaluar la relación con la infección por el virus de papiloma humano (HPV). Materiales y métodos. Se hizo un estudio transversal multicéntrico para detectar la infección por C. trachomatis en 1.282 mujeres mediante reacción en cadena de la polimerasa (PCR) convencional y el estuche comercial LightMix 480 HT CT/NG™ (Roche, Basilea, Suiza). Resultados. La prevalencia total de la infección por C. trachomatis fue de 4,1 % (IC95%2,9-5,3). Se encontró una relación significativa de la infección con la edad, el consumo de cigarrillo y el uso de anticonceptivos hormonales. Conclusión. La prevalencia de la infección es similar a la reportada en otros lugares del país y del mundo, siendo las mujeres más jóvenes lasmás afectadas. En cuanto a la presentación del HPV, no se encontró ningún tipo de relación con C. trachomatis.

Health-related quality of life of women after HPV testing as triage strategy for an abnormal Pap smear: a nested randomized pragmatic trial in a middle-income country.

BACKGROUND: Information obtained in studies on the impact of human papilloma virus (HPV) testing on health-related quality of life is contradictory. OBJECTIVE: To assess the impact on health-related quality of life of the HPV test, colposcopy, and cytology as triage strategies after a cytology with atypical squamous cells of undetermined significance (ASCUS) in Medellín, Colombia. METHODS: We carried out a nested analysis on the randomized pragmatic trial (ASCUS-COL). Women with ASCUS were assigned randomly to one of the 3 arms (Pap smear, colposcopy, HPV). Participants completed a questionnaire at baseline, two weeks after receiving the results of the triage tests and one year after the second questionnaire. We used the SF-36 to assess health-related quality of life. RESULTS: The sum score of the physical health component (PHC) and mental health component (MHC) increased significantly over time for the whole sample and there were no statistically significant differences between arms of PHC = survey 1: mean 52.4 (SD 8.21) vs. survey 3: mean 54.4 (SD 8.16) p < 0.0001 and of MHC = survey 1: mean 44.9 (SD 11.72) vs. survey 3: mean 48.1 (SD 11.20) p < 0.0001. A lower MHC occurred in women with lesser schooling, belonging to the public health care regimen, higher number of live births, and separated. A lower PHC was associated with the cytology arm, higher age, lesser schooling, and belonging to the subsidized regime. The risk of having depression went from 42% in the first survey to 26% in the third. CONCLUSION: The triage strategies affected health-related quality of life in the same manner. ClinicalTrials.gov Identifier: NCT02067468.

Psychosocial impact of inclusion of HPV test on the management of women with atypical squamous cells of undetermined significance: a study within a randomised pragmatic trial in a middle-income country.

Objective: To assess the psychosocial impact of human papillomavirus (HPV) testing, colposcopy, and Pap-smear, as triage strategies after a Pap-smear with atypical squamous cells of undetermined significance (ASCUS). We also sought to evaluate the psychosocial impact based on the results of the strategies. Methods: Nested within a randomised pragmatic trial, which compared an immediate colposcopy, repeat Pap-smear, and high risk HPV test, we enrolled 675 women between 2012 and 2014. Participants completed surveys at enrollment, two weeks after triage test results, and 1 year thereafter to assess cervical cancer and HPV knowledge, self-esteem, anxiety and HPV impact (HIP). Results: Knowledge, self-esteem, anxiety and HIP improved with no differences among arms. At the baseline, 31.4% and 32.7% of the participants had state anxiety and trait anxiety, respectively, which decreased to 10.7% and 13.3% in the last survey. Compared to HPV-negative women, HPV-positive women in the second survey had worse HIP scores (HPV-: M 22.9 [SD: 15.20]; HPV+: M 35.9 [SD: 19.91]; p < 0.001), trait anxiety (HPV-: M 15.4 [SD 12.73]; HPV+: M 22.9 [SD 13.29]; p = 0.001), and state anxiety (HPV-: M 10.7 [SD 11.25]; HPV+: M 21.4 [SD 14.81]; p < 0.001). Conclusions: HPV testing as a triage strategy for women with ASCUS does not differ from colposcopies or Pap-smears in terms of psychosocial outcomes.

High Rate of Infection by Only Oncogenic Human Papillomavirus in Amerindians.

Human papillomavirus (HPV), an etiological agent of cervical cancer (CC), has infected humans since ancient times. Amerindians are the furthest migrants out of Africa, and they reached the Americas more than 14,000 years ago. Some groups still remain isolated, and some migrate to towns, forming a gradient spanning urbanization. We hypothesized that, by virtue of their history, lifestyle, and isolation from the global society, remote Amerindian women have lower HPV diversity than do urban women (Amerindian or mestizo). Here we determined the diversity of the 25 most relevant cervical HPV types in 82 Amerindians spanning urbanization (low, medium, and high, consistent with the exposure to urban lifestyles of the town of Puerto Ayacucho in the Venezuelan Amazonas State), and in 29 urban mestizos from the town. Cervical, anal, oral, and introitus samples were taken, and HPVs were typed using reverse DNA hybridization. A total of 23 HPV types were detected, including 11 oncogenic or high-risk types, most associated with CC. Cervical HPV prevalence was 75%, with no differences by group, but Amerindians from low and medium urbanization level had significantly lower HPV diversity than mestizos did. In Amerindians, but not in mestizos, infections by only high-risk HPVs were higher than coinfections or by exclusively low-risk HPVs. Cervical abnormalities only were observed in Amerindians (9/82), consistent with their high HPV infection. The lower cervical HPV diversity in more isolated Amerindians is consistent with their lower exposure to the global pool, and transculturation to urban lifestyles could have implications on HPV ecology, infection, and virulence.IMPORTANCE The role of HPV type distribution on the disparity of cervical cancer (CC) incidence between human populations remains unknown. The incidence of CC in the Amazonas State of Venezuela is higher than the national average. In this study, we determined the diversity of known HPV types (the viral agent of CC) in Amerindian and mestizo women living in the Venezuelan Amazonas State. Understanding the ecological diversity of HPV in populations undergoing lifestyle transformations has important implication on public health measures for CC prevention.

Unexpected inverse correlation between Native American ancestry and Asian American variants of HPV16 in admixed Colombian cervical cancer cases.

BACKGROUND: European (E) variants of HPV 16 are evenly distributed among world regions, meanwhile Non-European variants such as European-Asian (EAs), Asian American (AA) and African (Af) are mostly confined to Eastern Asia, The Americas and African regions respectively. Several studies have shown that genetic variation of HPV 16 is associated with the risk of cervical cancer, which also seems to be dependent on the population. This relationship between ethnicity and variants have led to the suggestion that there is co-evolution of variants with humankind. Our aim was to evaluate the relationship between the individual ancestry proportion and infection with HPV 16 variants in cervical cancer. METHODS: We examined the association between ancestry and HPV 16 variants in samples of 82 cervical cancer cases from different regions of Colombia. Individual ancestry proportions (European, African and Native American) were estimated by genotyping 106 ancestry informative markers. Variants were identified by PCR amplification of the E6 gene, followed by reverse line blot hybridization (RLB) with variants specific probes. RESULTS: Overall European (E) and Asian American (AA) variants frequency was 66.5% and 33.5% respectively. Similar distribution was observed in cases with higher proportions of European or African ancestry. A higher Native American ancestry was significantly associated with higher frequency of E variants (median ancestry>23.6%, Age and place of birth adjusted OR: 3.55, 95% CI: 1.26-10.03, p=0.01). Even further, an inverse geographic correlation between Native American ancestry and frequency of infections with AA variants was observed (ρ=-0.825, p=0.008). Regions with higher proportion of Native American ancestry had a lower frequency of AA variants of HPV 16. CONCLUSIONS: This study suggests replacement of AA variants by E variants of human papillomavirus 16 in cervical cancer cases with high Native American ancestry.

Immunosuppression in cervical cancer with special reference to arginase activity.

INTRODUCTION: Cervical cancer is characterized by an immunosuppressive microenvironment and a Th2-type cytokine profile. Expression of arginase (ASE), the enzyme that converts L-arginine into L-ornithine and urea, is stimulated by Th2-type cytokines. OBJECTIVE: To assess the association of ASE activity and L-Arg metabolism products with cervical cancer. METHODS: Sera of 87 and 41 women with histologically confirmed by colposcopy-directed biopsy SCC and CIN3 respectively and 79 with normal cytology or Low-Grade Squamous Intraepithelial Lesion (LSIL), were evaluated. Cytokines were measured using Milliplex Human cytokine/chemokine kit. Arginase (ASE) activity was determined using an enzymatic assay. Levels of L-arginine, L-ornithine, putrescine and spermine were determined by HPLC. RESULTS: Significantly higher levels of ASE activity were observed in women with CIN3 (age-adjusted OR: 24.3; 95%CI: 3.82-155) and SCC (AOR: 9.8; 95%CI: 2.34-40.8). As expected, possibly due to high levels of ASE activity, higher levels of l-Arg were negatively associated with CIN3 (AOR: 0.03; 95%CI: 0.004-0.19) and SSC (AOR: 0.06; 95%CI: 0.02-0.24). Consistent with the role of ASE in the conversion of L-arginine to L-ornithine and polyamine production therefrom, women with cervical cancer had higher levels of spermine and putrescine. A correlation analysis revealed a significant albeit weak relationship between high levels of IL-10 and high levels of ASE (Pearson r=0.32, p-value=0.003) in women with cervical cancer. CONCLUSION: This study indicates that ASE activity and L-Arg degradation mechanisms of immunosuppression are present in cervical cancer. The results foster research in the design of possible strategies to inhibit ASE activity for therapy of cervical cancer.

Reproducibilidad en la lectura de un set de placas de citología cérvico-uterinas en cuatro centros especializados de Medellín, Antioquia / Reproducibility of reading a set of cervical cytology smears in four specialized centers in Medellin, Antioquia

OBJETIVO: evaluar el grado de reproducibilidad en la lectura de placas de citología cérvico-uterina entre cuatro centros de lectura especializados de la ciudad de Medellín, Colombia. METODOLOGIA: 181 placas de citología cérvico-uterina provenientes de un estudio de prevalencia de anormalidades citológicas en Pueblorrico, Antioquia, se sometieron a lectura en cuatro centros especializados de Medellín. Se le pidió a cada centro que realizara una lectura rutinaria manteniendo el estudio en ciego por medio de recodificación de las placas, evitando que se filtrara información entre centros. Se calculó la concordancia general y el índice kappa de Fleiss. RESULTADOS : de las 181 placas, sólo en 55 placas los 4 centros concordaron en el resultado, obteniéndose un porcentaje de concordancia global del 30% y un índice kappa global de 0,31. Según la escala de Fleiss, se observó una baja reproducibilidad en la lectura de las placas citológicas entre los cuatro centros involucrados en el estudio. La concordancia por pares de centros presentó índices de kappa entre 0,3 a 0,7. CONCLUSION:existe una alta variabilidad en la interpretación de los resultados citológicos entre los centros estudiados. Es necesario implementar procesos de entrenamiento y unificación de criterios de lecturas de la citología cervical en nuestro medio.

OBJECTIVE: to assess the degree of reproducibility in the reading of cervical cytology smears among four specialized reading centers at Medellin, Colombia.. METHODOLOGY: 181 cervical cytology smears from a study on the prevalence of cytological abnormalities in Pueblorrico, a town located in the southwestern region of the state of Antioquia in Colombia, were re-read by four specialized centers in Medellin. Each center was asked to conduct a blind routine reading of the smears to avoid disclosure of information between centers. The reproducibility was measured by percentage agreement and kappa. RESULTS :of 181 smears only 55 matched across all 4 centers, with an overall concordance rate of 30% and an overall kappa of 0.31. According to Fleiss scale, poor reproducibility was observed. The concordance between pairs of centers ranged between 0.3 y 0.7. DISCUSSION:there is a high variability in the interpretation of cytological results among centers in Medellin. It is necessary to implement training processes and to unify readings for cervical cytology criteria.

Time trends of human papillomavirus types in invasive cervical cancer, from 1940 to 2007.

Contribution over time of human papillomavirus (HPV) types in human cancers has been poorly documented. Such data is fundamental to measure current HPV vaccines impact in the years to come. We estimated the HPV type-specific distribution in a large international series of invasive cervical cancer (ICC) over 70 years prior to vaccination. Paraffin embedded ICC cases diagnosed between 1940 and 2007 were retrieved from eleven countries in Central-South America, Asia and Europe. Included countries reported to have low-medium cervical cancer screening uptake. Information on age at and year of diagnosis was collected from medical records. After histological confirmation, HPV DNA detection was performed by SPF-10/DEIA/LiPA25 (version1). Logistic regression models were used for estimating the adjusted relative contributions (RC) of HPV16 and of HPV18 over time. Among 4,771 HPV DNA positive ICC cases, HPV16 and HPV18 were the two most common HPVs in all the decades with no statistically significant variations of their adjusted-RC from 1940-59 to 2000-07 (HPV16-from 61.5 to 62.1%, and HPV18-from 6.9 to 7.2%). As well, the RC of other HPV types did not varied over time. In the stratified analysis by histology, HPV16 adjusted-RC significantly increased across decades in adenocarcinomas. Regarding age, cases associated to either HPV16, 18 or 45 were younger than those with other HPV types in all the evaluated decades. The observed stability on the HPV type distribution predicts a high and stable impact of HPV vaccination in reducing the cervical cancer burden in future vaccinated generations.

Clinical characteristics and HPV type in recurrent respiratory papillomatosis in Colombia.

OBJECTIVE: Describe factors associated with aggressive forms of recurrent respiratory papillomatosis (RRP). MATERIALS AND METHODS: One hundred eighty-nine RRP cases diagnosed between 1985 and 2009 were identified in pathological records. HPV was detected by the SPF-10 method with broad spectrum primers, (version 1). RESULTS: 113 patients had only one surgery (less aggressive) and 76, two or more interventions (more aggressive). The likelihood of aggressive lesions decreased with increasing age at diagnosis and HPV-11 was associated with no significant increase in the risk of aggressiveness. CONCLUSIONS: The age at diagnosis was the main determinant of RRP aggressiveness.

Clinical characteristics and HPV type in recurrent respiratory papillomatosis in Colombia / Características clínicas y genotipo de VPH en papilomatosis respiratoria recurrente en Colombia

Objective. Describe factors associated with aggressive forms of recurrent respiratory papillomatosis (RRP). Materials and methods. One hundred eighty-nine RRP cases diagnosed between 1985 and 2009 were identified in pathological records. HPV was detected by the SPF-10 method with broad spectrum primers, (version 1). Results. 113 patients had only one surgery (less aggressive) and 76, two or more interventions (more aggressive). The likelihood of aggressive lesions decreased with increasing age at diagnosis and HPV-11 was associated with no significant increase in the risk of aggressiveness. Conclusions. The age at diagnosis was the main determinant of RRP aggressiveness.

Objetivo. Describir factores asociados con formas agresivas de papilomatosis respiratoria recurrente (PRR). Material y métodos. Se identificaron 189 casos de PRR diagnosticados entre 1985-2009 en registros patológicos. VPH fue detectado por el método SPF-10 con cebadores de amplio espectro, (versión 1). Resultados. 113 casos presentaron una intervención quirúrgica (menos agresivas) y 76, dos o más intervenciones (más agresivas). La probabilidad de lesiones agresivas disminuyó con el aumento de la edad al momento del diagnóstico y el VPH-11 se asoció con aumento no significativo del riesgo de agresividad. Conclusiones. La edad al momento del diagnóstico fue el principal determinante de la agresividad de PRR.

Human papillomavirus types in cases of squamous cell carcinoma of head and neck in Colombia.

UNLABELLED: Estimating the type-specific prevalence of human papillomavirus (HPV) in head and neck cancer (HNSCC) is helpful in predicting the impact of HPV immunization. OBJECTIVE: To estimate the overall prevalence, and gender and age-specific prevalence of HPV in HNSCC. METHOD: This cross sectional retrospective study was carried out in four pathology laboratories of Medellin, Colombia. HPV testing was performed by GP5+/6+ PCR-based RLB and HPV 16 and 18 type-specific PCR. RESULTS: 175 primary HNSCC cases consecutively diagnosed between 1999 and 2008 with confirmed diagnosis and amplifiable DNA were included. Overall HPV prevalence was 18.9%. HPV was found in 23.9%, 17.5% and 13.3% of the oral cavity, larynx and oropharynx cases respectively. Among HPV positive cases, 82% were HPV 16 and 18% were HPV 18. No other HPV genotypes were identified. Most patients were males. Male patients were younger that their female counterparts, particularly in oral cavity cancer cases. CONCLUSION: HPV 16 and 18 genotypes were found in nearly 20% of HNSCC cases in Colombian patients. The impact of HPV vaccination for the prevention of HNSCC in this population deserves further evaluation.

Genótipos de vírus de papiloma humano em carcinoma de células escamosas de cabeça e pescoço na Colômbia / Human papillomavirus types in cases of squamous cell carcinoma of head and neck in Colombia

Estimar a prevalência de tipos do vírus de papiloma humano (HPV) em câncer de cabeça e pescoço (CCP) é relevante para se prever o impacto da vacina contra o HPV. OBJETIVO: Estimar a prevalência global, por gênero e idade, do vírus do HPV em CCP. MÉTODO: Estudo transversal, retrospectivo envolvendo quatro laboratórios de patologia de Medellín, Colômbia. O exame utilizado foi o PCR GP5+/6+ e hibridização reversa. Além disso, os HPV 16 e 18 foram identificados utilizando-se PCR específica para esses tipos. RESULTADOS: Foram incluídos 175 casos primários de CCP, consecutivamente diagnosticados entre 1999 e 2008, com diagnóstico confirmado e DNA amplificado. A prevalência de HPV foi de 18,9%. O HPV foi encontrado em 23,9%, 17,5% e 13,3% dos casos de cavidade oral, laringe e orofaringe, respectivamente. Entre os casos de VPH+, 82% foram HPV 16 e 18% HPV18. A maioria dos casos foi de pessoas do sexo masculino. Nos homens, a idade de diagnóstico foi menor do que nas mulheres, principalmente naqueles de acometimento na cavidade oral. CONCLUSÃO: Os HPV 16 e 18 foram encontrados em quase 20% desses casos de CCP. O impacto da vacinação contra o HPV para a prevenção desse câncer na população merece maiores estudos.

Estimating the type-specific prevalence of human papillomavirus (HPV) in head and neck cancer (HNSCC) is helpful in predicting the impact of HPV immunization. OBJECTIVE: To estimate the overall prevalence, and gender and age-specific prevalence of HPV in HNSCC. METHOD: This cross sectional retrospective study was carried out in four pathology laboratories of Medellin, Colombia. HPV testing was performed by GP5+/6+ PCR-based RLB and HPV 16 and 18 type-specific PCR. RESULTS: 175 primary HNSCC cases consecutively diagnosed between 1999 and 2008 with confirmed diagnosis and amplifiable DNA were included. Overall HPV prevalence was 18.9%. HPV was found in 23.9%, 17.5% and 13.3% of the oral cavity, larynx and oropharynx cases respectively. Among HPV positive cases, 82% were HPV 16 and 18% were HPV 18. No other HPV genotypes were identified. Most patients were males. Male patients were younger that their female counterparts, particularly in oral cavity cancer cases. CONCLUSION: HPV 16 and 18 genotypes were found in nearly 20% of HNSCC cases in Colombian patients. The impact of HPV vaccination for the prevention of HNSCC in this population deserves further evaluation.

Location and Density of Immune Cells in Precursor Lesions and Cervical Cancer.

Only a small proportion of women infected with Human Papillomavirus (HPV) develop cervical cancer. Host immune response seems to play a role eliminating the viral infection and preventing progression to cancer. Characterization of tumor infiltrating lymphocytes (TILs) in cervical pre-neoplastic lesions and cervical cancer may be helpful to understand the mechanisms that mediate this protection. The aim of this study was to determine if there are differences in the localization and density (cells/mm(2)) of CD8+ T-cells, CD4+ T-cells and Tregs (CD25 + Foxp3+) in cervical pre-neoplastic lesions and cervical cancer. Immunohistochemical analysis of sections of 96 (26 CIN1, 21 CIN2, 25 CIN3, and 24 SCC) samples revealed that regardless of CIN grades, CD8+ T-cells are more abundant than CD4+, CD25+ and Foxp3+ cells in both the stroma and epithelium. There was a higher density of CD8+ cells in the stroma of cervical cancer compared to CIN3 (OR = 4.20, 95% CI 1.2-15), CIN2 (OR = 7.86, 95% CI 1.7-36.4) and CIN1 (OR = 4.25, 95% CI 1.1-17). Studies evaluating whether these cells are recruited before or after cancer progression will be helpful to understand the role of these cells in the natural history of HPV-induced lesions.

Human papillomavirus genotype detection in recurrent respiratory papillomatosis (RRP) in Colombia.

BACKGROUND: Knowledge on human papillomavirus (HPV) genotype distribution in recurrent respiratory papillomatosis (RRP) is essential to assess the impact of HPV vaccine. It is provided information for Colombia. METHODS: In all, 189 RRP primary cases diagnosed between 1985 and 2009 were identified from 5 pathology laboratories of Cali and Medellin, Colombia. HPV DNA testing in 129 cases that fulfilled inclusion criteria (available paraffin blocks, amplifiable DNA, and confirmed histologic diagnosis of RRP) was performed by the SPF-10/LiPA25 assay (version 1). RESULTS: Of all cases 36.1% were juvenile (<12 years old) and a majority of adults were males (p = .09); 95% of cases were HPV positive. HPV 6, 11, and 16 contributed to 69%, 27.1%, and 7.8% of all HPV positive cases. Twelve cases (9.3%) showed multiple infections; 8 of these were HPV 6 or 11 positive. CONCLUSIONS: HPV prophylactic vaccine including HPV 6 and 11 may have a major impact against RRP.

Age-specific seroprevalence of human papillomavirus 16, 18, 31, and 58 in women of a rural town of Colombia.

OBJECTIVE: The study's objective was to estimate human papillomavirus (HPV) genotype-specific seroprevalence to determine population HPV exposure and inform vaccine policy. METHODS: This study is a cross-sectional prevalence survey of 878 women of Pueblorrico, a rural town of Colombia. A standardized questionnaire was used to obtain information on demographic characteristics, sexual and reproductive history, and smoking habits. Seropositivity to HPV-16, -18, -31, and -58 was determined by virus-like particles in an enzyme-linked immunosorbent assay. RESULTS: Overall seropositivity to any HPV genotype was 27.9%. The combined seroprevalence of women 15 to 19 and 20 to 24 years old was 35.4% (95% confidence interval [CI], 25.9-46.2) and 36.0% (95% CI, 27.7-45.3), respectively. Seroprevalence for HPV-16 was 17% (95% CI, 14.6-19.6); for HPV-18, 9.8% (95% CI, 8.0-11.9); for HPV-31, 11.4% (95% CI, 9.5-13.7); and for HPV 58, 12.5% (95% CI, 10.5-14.9). Higher HPV seropositivity was associated with the lifetime number of occasional sexual partners (odds ratio, 3.05; 95% CI, 1.26-7.37) and having more than 2 regular sexual partners (odds ratio, 3.00; 95% CI, 1.21-7.45) in women younger than 44 and older than 45 years old, respectively. Use of oral contraceptives and tobacco/cigarettes was significantly associated with reduced HPV seropositivity in women older than 45 but not in women younger than 44 years old. CONCLUSIONS: Human papillomavirus seropositivity is associated with measures of sexual behavior, particularly a greater lifetime number of sexual partners. Hormonal and tobacco/cigarette use may be factors influencing the HPV seropositivity in women older than 45 years old.

Tendencias e indicadores sociales de la mortalidad por cáncer de mama y cuello uterino: Antioquia, Colombia, 2000-2007 / Trends and social indicators of both mortality breast cancer and cervical cancer in Antioquia, Colombia, 2000-2007

OBJETIVO: Estimar tasas estandarizadas por edad (TEE) de mortalidad por cáncer de mama y cérvix 2000-2007 y explorar indicadores sociales que expliquen la variabilidad de las tasas. MATERIAL Y MÉTODOS: Las TEE de mortalidad se estimaron por el método directo y mediante regresión lineal se relacionaron con indicadores sociales por subregión. RESULTADOS: La TEE de cáncer de mama en Antioquia fue 11.3 por 100 000 mujeres-año y para cáncer cervical 9.1. En Medellín, la TEE de cáncer de mama fue 12.5, 1.8 veces la tasa de cáncer cervical. Se observó una disminución del cáncer cervical en Medellín (valor-p=0.03) entre 2000 y 2007, pero no en el resto de Antioquia. La mortalidad de cáncer cervical se relacionó con el porcentaje de miseria (valor-p=0.0003). CONCLUSIONES: La mortalidad por estas neoplasias ha permanecido constante en Antioquia, con una amplia variación de la mortalidad por cáncer cervical por subregión asociada con niveles de pobreza.

OBJECTIVE: To estimate the mortality age-standardized rates (ASR) for breast and cervical cancer from 2000-2007 and explore social indicators that explain the variability of rates in Antioquia. MATERIAL AND METHODS: The ASR was estimated by the direct method and linear regression was used to relate social indicators with rates by subregion. RESULTS: Breast and cervical cancer mortality ASRs in Antioquia were 11.3 and 9.1 per 100 000 woman-years respectively. In Medellin, the breast cancer mortality ASR was 12.5, 1.8 times the rate of cervical cancer. A decrease of cervical cancer ASR between 2000 and 2007 was observed in Medellin (p-value=0.03) but not in the rest of Antioquia. Cervical cancer mortality ASR was related to the percentage of poverty (p-value=0.0003). CONCLUSIONS: Mortality due to these neoplasms has remained constant in Antioquia. The wide variation in mortality from cervical cancer between regions seems to be associated with poverty.