Factores de riesgo asociados con la artrosis de rodilla: revisión sistemática de la literatura / Risk factors for knee osteoarthritis: a systematic review of the literature

Introducción: la osteoartritis de rodilla (OR) se define como una enfermedad crónica, inflamatoria, degenerativa y progresiva, caracterizada por el deterioro del cartílago articular. Tiene manifestaciones clínicas y etiológicas diferentes según el grupo etario y se encuentra asociada con múltiples factores que intervienen en la fisiopatología, entre los que están: edad, raza, sexo, sobrepeso, obesidad y síndrome metabólico. Objetivo: determinar los factores de riesgo que influyen en el proceso degenerativo de la OR en la adultez temprana y tardía. Materiales y métodos: revisión sistemática de la literatura científica en diferentes bases de datos que incluyeron estudios de cohorte, transversales, casos y controles, evaluando los factores de riesgo predisponentes. Resultados: se seleccionaron 50 artículos que cumplieron con los criterios, identificando diferentes factores que afectan el desarrollo o progresión de la OR como las alteraciones metabólicas, sistémicas y estilo de vida que influyen en esta patología, además de factores modificables y no modificables. Conclusión: la OR es una afección de carácter multifactorial, donde la obesidad, la hipertensión arterial (HTA), el índice de masa corporal (IMC) elevado, los niveles altos de LDL, la debilidad muscular e incluso la profesión del paciente, son los principales factores predisponentes para desarrollar o aumentar su progresión.

Introduction: knee osteoarthritis (OA) is defined as a chronic, inflammatory, degenerative, and progressive disease, characterized by articular cartilage deterioration. It has different clinical and etiological manifestations according to age group and multiple contributing pathophysiological factors, among which are: age, race, gender, overweight, obesity and metabolic syndrome. Objective: to determine the risk factors leading to knee OA degenerative process in early and late adulthood. Materials and methods: a systematic review of the scientific literature which included cohort cross-sectional case-control studies evaluating knee OA predisposing risk factors, in different databases. Results: fifty articles which met the criteria and identified the various predisposing factors for developing knee OA such as metabolic, systemic and lifestyle alterations, in addition to modifiable and non-modifiable factors, were selected. Conclusion: knee OA is a multifactorial condition, where obesity, hypertension, high body mass index (BMI), high LDL levels, poor muscular strength and even the patient ́s occupation are the main predisposing factors for developing or increasing knee OA progression.

Characterization of dyspnea in chronic diseases and heart failure in patients in a Family Health Program / Caracterización de la disnea en pacientes con enfermedades crónicas e insuficiencia cardíaca de un Programa de Salud Familiar

Abstract Background: Dyspnea is the most common symptom in heart failure. In the elderly, it is common in chronic obstructive pulmonary disease and depression. Objective: To estimate the prevalence of dyspnea on exertion, orthopnea and paroxysmal nocturnal dyspnea and its association with chronic diseases in primary care. Methods: A cross-sectional study, part of the Digitalis Study, including 633 individuals, between 45 to 99 years old, registered in a primary care program in Niteroi, Brazil. All participants underwent clinical evaluations, blood and urine collection, and responded to a questionnaire in a single day. Self-reports were used for the diagnosis of diseases. Results: Of the 633 individuals, 30% had dyspnea. In the crude analysis, chronic obstructive pulmonary disease showed the strongest associations with the three types of dyspnea, followed by depression and heart failure. Chronic obstructive pulmonary disease alone did not present any cases of paroxysmal nocturnal dyspnea, and heart failure alone showed a very strong relationship with this type of dyspnea. Conclusions: The different behavior of the associations of the types of dyspnea with major chronic diseases in patients in primary care can help in the better characterization of patients with heart failure.

Resumen Introducción: La disnea es el síntoma más común en la insuficiencia cardíaca. En los ancianos es común en la enfermedad pulmonar obstructiva crónica y la depresión. Objetivo: Estimar la prevalencia de disnea de esfuerzo, ortopnea y disnea paroxística nocturna y su asociación con enfermedades crónicas en la atención primaria. Métodos: Estudio transversal, parte del estudio Digitalis, que incluyó a 633 individuos, entre 45 y 99 años de edad, registrados en un programa de atención primaria en Niterói, Brasil. Todos los participantes se sometieron a evaluaciones clínicas, recolección de sangre y orina, y respondieron a un cuestionario en un solo día. Se usaron autorrelatos para el diagnóstico de las enfermedades. Resultados: De los 633 individuos, el 30% presentó disnea. En el análisis crudo la enfermedad pulmonar obstructiva crónica mostró las asociaciones más fuertes con los tres tipos de disnea, seguidos por la depresión y la insuficiencia cardíaca. La enfermedad pulmonar obstructiva crónica, evaluada de forma aislada, no presentó ningún caso de disnea paroxística nocturna, y la insuficiencia cardíaca por sí sola mostró una relación muy fuerte con este tipo de disnea. Conclusiones: El comportamiento diferente de las asociaciones de los tipos de disnea con las principales enfermedades crónicas en pacientes en atención primaria puede ayudar a una mejor caracterización de los pacientes con insuficiencia cardíaca.

[Evaluation of mortality after the analysis of the screening history in women diagnosed with infiltrating cervical cancer]. / Evaluación de fallos tras el análisis de la historia de cribado en mujeres diagnosticadas de cáncer infiltrante de cuello uterino.

OBJECTIVE: To assess the impact of screening history on the incidence of cervical cancer from 2000 to 2010 in Asturias. DESIGN: Retrospective study. LOCATION: All public hospitals in Asturias. MEAN MEASUREMENTS: From 374 women diagnosed with cervical cancer were retrieved. Clinical information, FIGO stage and all previous cytological data were extracted from clinical and histopathological records. Proportional differences were assessed using chi-square tests. Logistic regression analysis was used to estimate odds ratios and 95% confidence intervals. RESULTS: Women between 25 and 70years had no records of a previous cytology within 5.5years of cancer diagnosis in 65.6%. This proportion was related with older age, presence of symptoms and an advance tumor stage at diagnosis. Women over 70years old had no records of a previous cytology in 83.3%. CONCLUSION: An organized cervical cancer screening program and optimal quality of the system, monitored through audits, could help to reduce cervical cancer incidence and mortality in Asturias.

Poor Cervical Cancer Screening Attendance and False Negatives. A Call for Organized Screening.

OBJECTIVE: The objective of this study was to describe prior negative screening history and symptoms around the time of diagnosis of incident cervical cancer (CC) cases diagnosed between 2000 and 2010 within the Asturias public health system. METHODS: Records from 374 women diagnosed with CC between 2000 and 2010 from all public hospitals in Asturias were retrieved. Clinical information, FIGO stage and all previous cytological data were extracted from clinical and histopathological records. Proportional differences were assessed using chi-square tests. Logistic regression analysis was used to estimate odds ratios (OR) and 95% confidence intervals (CI). Inter-observer agreement in cytology was checked by comparing concordance values using k-statistics. RESULTS: No prior screening history was recorded in 60.7% of CC cases and its absence increased with age and advanced stage. Advanced stage (e.g., ≥ II) at diagnosis was associated with age (>50 years) and adenocarcinoma (ADC) compared to younger women and those with a squamous cell carcinoma (SCC). False negative smears were identified in 27.1% of women with CC (ADC 52.6% vs. SCC 16.2%, p<0.05). CONCLUSIONS: Absence of prior screening history was common among CC cases. Organized actions to reduce "under screening" and the use of highly sensitive HPV-based tests could be useful strategies in reducing the burden of CC in Asturias.

Role of Human Papillomavirus in Penile Carcinomas Worldwide.

BACKGROUND: Invasive penile cancer is a rare disease with an approximately 22 000 cases per year. The incidence is higher in less developed countries, where penile cancer can account for up to 10% of cancers among men in some parts of Africa, South America, and Asia. OBJECTIVE: To describe the human papillomavirus (HPV) DNA prevalence, HPV type distribution, and detection of markers of viral activity (ie, E6*I mRNA and p16(INK4a)) in a series of invasive penile cancers and penile high-grade squamous intraepithelial lesions (HGSILs) from 25 countries. A total of 85 penile HGSILs and 1010 penile invasive cancers diagnosed from 1983 to 2011 were included. DESIGN, SETTING, AND PARTICIPANTS: After histopathologic evaluation of formalin-fixed paraffin-embedded samples, HPV DNA detection and genotyping were performed using the SPF-10/DEIA/LiPA25 system, v.1 (Laboratory Biomedical Products, Rijswijk, The Netherlands). HPV DNA-positive cases were additionally tested for oncogene E6*I mRNA and all cases for p16(INK4a) expression, a surrogate marker of oncogenic HPV activity. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: HPV DNA prevalence and type distributions were estimated. RESULTS AND LIMITATIONS: HPV DNA was detected in 33.1% of penile cancers (95% confidence interval [CI], 30.2-36.1) and in 87.1% of HGSILs (95% CI, 78.0-93.4). The warty-basaloid histologic subtype showed the highest HPV DNA prevalence. Among cancers, statistically significant differences in prevalence were observed only by geographic region and not by period or by age at diagnosis. HPV16 was the most frequent HPV type detected in both HPV-positive cancers (68.7%) and HGSILs (79.6%). HPV6 was the second most common type in invasive cancers (3.7%). The p16(INK4a) upregulation and mRNA detection in addition to HPV DNA positivity were observed in 69.3% of HGSILs, and at least one of these HPV activity markers was detected in 85.3% of cases. In penile cancers, these figures were 22.0% and 27.1%, respectively. CONCLUSIONS: About a third to a fourth of penile cancers were related to HPV when considering HPV DNA detection alone or adding an HPV activity marker, respectively. The observed HPV type distribution reinforces the potential benefit of current and new HPV vaccines in the reduction of HPV-related penile neoplastic lesions. PATIENT SUMMARY: About one-third to one-quarter of penile cancers were related to human papillomavirus (HPV). The observed HPV type distribution reinforces the potential benefit of current and new HPV vaccines to prevent HPV-related penile neoplastic lesions.

Expression of p16/Ki-67 in ASC-US/LSIL or Normal Cytology with Presence of Oncogenic HPV DNA.

AIM: To determine if positive dual staining of p16/Ki-67 in cytology samples from women with atypical squamous cells of undetermined significance (ASC-US), low-grade squamous intraepithelial lesion (LSIL) or normal cytological reports with presence of high-risk human papillomavirus (HPV), helps in predicting the risk of developing high-grade cervical lesions during one-year of follow-up after a normal initial colposcopy. MATERIALS AND METHODS: One-hundred and sixty women with ASC-US, LSIL or otherwise normal cytology, but with the presence of high-risk HPV, were referred to the colposcopy Unit of our Hospital. Cytology and HPV testing were repeated and dual staining of p16/Ki-67 performed on a new cytological specimen, and subsequently patients were colposcopically assessed and prospectively followed-up for one year, after which the colposcopy was repeated. An optional intermediate colposcopical assessment after six months was also offered. RESULTS: Out of 143/160 women with a normal initial colposcopy, 13 were ultimately lost to follow-up. Out of the remaining 130, nine developed histologically verified cervical intraepithelial neoplasia or higher grade (CIN2+) lesions during the one-year follow-up period. Two thirds of them (6/9) were initially p16/Ki-67-positive. CONCLUSION: Biomarker detection may identify women at higher risk of CIN2+, and these women may benefit from early colposcopic assessment. Women who test negatively for the biomarkers could eventually follow a less aggressive protocol.

Manganese superoxide dismutase (SOD2/MnSOD)/catalase and SOD2/GPx1 ratios as biomarkers for tumor progression and metastasis in prostate, colon, and lung cancer.

The role of manganese-dependent superoxide dismutase (SOD2/MnSOD) during tumor progression has been studied for several decades with controversial results. While SOD2 downregulation was initially associated with tumor initiation and was proposed as a tumor suppressor gene, recent studies have reported that SOD2 might favor tumor progression and dissemination. To our knowledge this is the first time that changes in SOD2 expression in three different types of tumors, i.e., prostate, lung, and colon cancer, are studied by analyzing both SOD2 mRNA and protein levels in a total of 246 patients' samples. In prostate samples, SOD2 protein levels were also increased, especially in middle stage tumors. In the case of colon and lung tumors both mRNA and protein SOD2 levels were increased in malignant tissues compared to those in nontumor samples. More importantly, all metastases analyzed showed increased levels of SOD2 when compared to those of normal primary tissue and healthy adjacent tissue. Together, these results suggest that a common redox imbalance in these three types of tumor occurs at intermediate stages which then might favor migration and invasion, leading to a more aggressive cancer type. Consequently, the ratios SOD2/catalase and SOD2/Gpx1 could be considered as potential markers during progression from tumor growth to metastasis.

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.

Evaluation of p16(INK4a) overexpression in a large series of cervical carcinomas: concordance with SPF10-LiPA25 PCR.

The aims of this study were to assess the overexpression of p16 in formalin-fixed paraffin-embedded cervical carcinoma tissue blocks and to determine its concordance with the human papillomavirus (HPV) status using the SPF10-LiPA25 polymerase chain reaction System and its correlation with the histologic type of invasive cervical cancer (ICC) and individual HPV genotypes. A total of 205 retrospectively collected ICC cases were analyzed by p16 immunohistochemistry. HPV detection was performed by polymerase chain reaction using SPF10 broad-spectrum primers, followed by deoxyribonucleic acid enzyme immunoassay and genotyping by reverse hybridization line probe assay (LiPA25). Of 205, 188 analyzed (91.7%) ICC cases showed p16 overexpression, whereas 181 (83.3%) cases were HPV positive using HPV LiPA testing. One hundred and seventy four (84.9%) cases were both p16 and HPV LiPA positive, indicating a positive concordance of 89.9% between both techniques (κ index agreement of 0.43; P<0.001), and no statistically significant difference (McNemar test, P>0.05). Squamous cell carcinomas were strongly positive compared with the adenocarcinomas (93.6% vs. 75% of the cases, respectively). When performed on formalin-fixed paraffin-embedded cervical tissue specimens, the higher positivity rate of p16 immunohistochemistry as compared with HPV DNA testing may allow identifying HPV-related ICC cases in which HPV testing was negative.

Worldwide human papillomavirus genotype attribution in over 2000 cases of intraepithelial and invasive lesions of the vulva.

BACKGROUND: Human papillomavirus (HPV) contribution in vulvar intraepithelial lesions (VIN) and invasive vulvar cancer (IVC) is not clearly established. This study provides novel data on HPV markers in a large series of VIN and IVC lesions. METHODS: Histologically confirmed VIN and IVC from 39 countries were assembled at the Catalan Institute of Oncology (ICO). HPV-DNA detection was done by polymerase chain reaction using SPF-10 broad-spectrum primers and genotyping by reverse hybridisation line probe assay (LiPA25) (version 1). IVC cases were tested for p16(INK4a) by immunohistochemistry (CINtec histology kit, ROCHE). An IVC was considered HPV driven if both HPV-DNA and p16(INK4a) overexpression were observed simultaneously. Data analyses included algorithms allocating multiple infections to calculate type-specific contribution and logistic regression models to estimate adjusted prevalence (AP) and its 95% confidence intervals (CI). RESULTS: Of 2296 cases, 587 were VIN and 1709 IVC. HPV-DNA was detected in 86.7% and 28.6% of the cases respectively. Amongst IVC cases, 25.1% were both HPV-DNA and p16(INK4a) positive. IVC cases were largely keratinising squamous cell carcinoma (KSCC) (N=1234). Overall prevalence of HPV related IVC cases was highest in younger women for any histological subtype. SCC with warty or basaloid features (SCC_WB) (N=326) were more likely to be HPV and p16(INK4a) positive (AP=69.5%, CI=63.6-74.8) versus KSCC (AP=11.5%, CI=9.7-13.5). HPV 16 was the commonest type (72.5%) followed by HPV 33 (6.5%) and HPV 18 (4.6%). Enrichment from VIN to IVC was significantly high for HPV 45 (8.5-fold). CONCLUSION: Combined data from HPV-DNA and p16(INK4a) testing are likely to represent a closer estimate of the real fraction of IVC induced by HPV. Our results indicate that HPV contribution in invasive vulvar cancer has probably been overestimated. HPV 16 remains the major player worldwide.

RETRACTED: S-allyl cysteine protects against 6-hydroxydopamine-induced neurotoxicity in the rat striatum: involvement of Nrf2 transcription factor activation and modulation of signaling kinase cascades.

Pharmacological activation at the basal ganglia of the transcription factor Nrf2, guardian of redox homeostasis, holds a strong promise for the slow progression of Parkinson's disease (PD). However, a potent Nrf2 activator in the brain still must be found. In this study, we have investigated the potential use of the antioxidant compound S-allyl cysteine (SAC) in the activation of Nrf2 in 6-hydoxydopamine (6-OHDA)-intoxicated rats. In the rat striatum, SAC by itself promoted the Nrf2 dissociation of Keap-1, its nuclear translocation, the subsequent association with small MafK protein, and further binding of the Nrf2/MafK complex to ARE sequence, as well as the up-regulation of Nrf2-dependent genes encoding the antioxidant enzymes HO-1, NQO-1, GR, and SOD-1. In vivo and in vitro experiments to identify signaling pathways activated by SAC pointed to Akt as the most likely kinase participating in Nrf2 activation by SAC. In PC12 cells, SAC stimulated the activation of Akt and ERK1/2 and inhibited JNK1/2/3 activation. In the rat striatum, the SAC-induced activation of Nrf2 is likely to contribute to inhibit the toxic effects of 6-OHDA evidenced by phase 2 antioxidant enzymes up-regulation, glutathione recovery, and attenuation of reactive oxygen species (ROS), nitric oxide (NO), and lipid peroxides formation. These early protective effects correlated with the long-term preservation of the cellular redox status, the striatal dopamine (DA) and tyrosine hydroxylase (TH) levels, and the improvement of motor skills. Therefore, this study indicates that, in addition to direct scavenging actions, the activation of Nrf2 by SAC might confer neuroprotective responses through the modulation of kinase signaling pathways in rodent models of PD, and suggests that this antioxidant molecule may have a therapeutic value in this human pathology.

Comparison of 2 different PCR-based technologies for the detection of human papilloma virus from paraffin-embedded tissue: genómica clinical arrays versus SPF(10)-LiPA(25).

The great interest in molecular epidemiology of human papilloma virus (HPV) in cervical cancer led us to perform a thorough evaluation of 2 polymerase chain reaction (PCR)-based methods for the detection of HPV in archival formalin-fixed paraffin-embedded (FFPE) samples. Thus, the aim of this study was to compare HPV detection in FFPE samples that have histopathologic diagnosis of invasive cervical cancer using SPF10 broad-spectrum primers PCR followed by DNA enzyme immunoassay and LiPA25 (version 1: Labo Biomedical products, Rijswijk, The Netherlands version 1) and the Papillomavirus Clinical Arrays technique (Genómica, Tres Cantos, Madrid, Spain). In this study, 235 biopsies with histopathologic diagnosis of invasive cervical cancer were analyzed for the detection and genotyping of HPV by LiPA25 SPF10-PCR System (version 1) and Papillomavirus Clinical Arrays technique. The detection of HPV DNA with Genómica technique was 75.1%, and 91.9% with LiPA25 SPF10-PCR. The Genómica technique detected a higher percentage of multiple infections (35%) than LiPA25 (8.9%), with a very low agreement for the detection of multiple infections between them (P>0.05). Our study highlights an important difference between 2 PCR-based methods for detection and genotyping of HPV. LiPA25 SPF10-PCR technology may be more adequate than Genómica for the detection of HPV DNA when using FFPE tissue.

Human papillomavirus genotype distribution in cervical cancer cases in Spain. Implications for prevention.

OBJECTIVE: Human papillomavirus (HPV) genotype distribution in invasive cervical cancer (ICC) is critical to guide the introduction and to assess the impact of HPV prophylactic vaccines. This study aims to provide specific information for Spain. METHODS: 1043 histological confirmed ICC cases diagnosed from 1940 to 2007 from six Spanish regions were assembled. HPV DNA detection was performed by SPF(10) broad-spectrum PCR followed by deoxyribonucleic acid enzyme immunoassay and genotyping by reverse hybridization line probe assay (LiPA(25)) (version 1). RESULTS: Of 1043 ICC cases, 904 were HPV DNA positive (adjusted prevalence: 89.1%). The eight most common types, in decreasing order, were HPV 16, 18, 33, 31, 45, 35, 52 and 56, accounting for more than 90% of cases. HPV 16 and 18 contributed to 72.4% of all HPV positive ICC cases. In cervical adenocarcinomas, this contribution increased up to 94%. HPV 16 and 18 relative contributions showed a stable pattern over the 60 year study period. HPV 45, 18 and 16-positive ICC cases presented at younger ages than cases with other HPV types (adjusted mean age: 43.8, 45.2, 52.6 and 57.7 years, respectively). CONCLUSIONS: HPV 16 and 18 accounted together for a 72.4% of positive cases, with no statistically significant changes in their relative contributions over the last decades. In 94% of cervical adenocarcinomas we identified at least one of the two HPV types included in the current vaccines (HPV 16/18). Results suggest a major impact of HPV vaccines on reduction of ICC burden in Spain in the HPV vaccinated cohorts.

Rapid and sustained response to tocilizumab, anti-interleukin-6 receptor antibody, in a patient with nephrotic syndrome secondary to systemic juvenile idiopathic arthritis-related amyloidosis.

AA amyloidosis, or secondary amyloidosis, is a rare but serious complication of chronic inflammatory diseases. Chronic inflammatory arthritis is the commonest cause of AA amyloidosis and, when the latter appears, treatment can be frustrating. Deposition of fibrils, derived from circulating acute-phase reactant serum amyloid A protein (SAA), in the kidneys can lead to proteinuria and progressive loss of renal function. We describe the case of a 14-year-old female with systemic juvenile idiopathic arthritis who developed nephrotic syndrome secondary to AA amyloidosis; while she was unresponsive to all measures, including anti-tumour necrosis factor therapy, treatment with tocilizumab, an anti-human interleukin-6 receptor antibody, immediately normalized the SAA and reversed the nephrotic syndrome. We discuss this new therapeutic approach.

Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study.

BACKGROUND: Knowledge about the distribution of human papillomavirus (HPV) genotypes in invasive cervical cancer is crucial to guide the introduction of prophylactic vaccines. We aimed to provide novel and comprehensive data about the worldwide genotype distribution in patients with invasive cervical cancer. METHODS: Paraffin-embedded samples of histologically confirmed cases of invasive cervical cancer were collected from 38 countries in Europe, North America, central South America, Africa, Asia, and Oceania. Inclusion criteria were a pathological confirmation of a primary invasive cervical cancer of epithelial origin in the tissue sample selected for analysis of HPV DNA, and information about the year of diagnosis. HPV detection was done by use of PCR with SPF-10 broad-spectrum primers followed by DNA enzyme immunoassay and genotyping with a reverse hybridisation line probe assay. Sequence analysis was done to characterise HPV-positive samples with unknown HPV types. Data analyses included algorithms of multiple infections to estimate type-specific relative contributions. FINDINGS: 22,661 paraffin-embedded samples were obtained from 14,249 women. 10,575 cases of invasive cervical cancer were included in the study, and 8977 (85%) of these were positive for HPV DNA. The most common HPV types were 16, 18, 31, 33, 35, 45, 52, and 58 with a combined worldwide relative contribution of 8196 of 8977 (91%, 95% CI 90-92). HPV types 16 and 18 were detected in 6357 of 8977 of cases (71%, 70-72) of invasive cervical cancer. HPV types 16, 18, and 45 were detected in 443 of 470 cases (94%, 92-96) of cervical adenocarcinomas. Unknown HPV types that were identified with sequence analysis were 26, 30, 61, 67, 69, 82, and 91 in 103 (1%) of 8977 cases of invasive cervical cancer. Women with invasive cervical cancers related to HPV types 16, 18, or 45 presented at a younger mean age than did those with other HPV types (50·0 years [49·6-50·4], 48·2 years [47·3-49·2], 46·8 years [46·6-48·1], and 55·5 years [54·9-56·1], respectively). INTERPRETATION: To our knowledge, this study is the largest assessment of HPV genotypes to date. HPV types 16, 18, 31, 33, 35, 45, 52, and 58 should be given priority when the cross-protective effects of current vaccines are assessed, and for formulation of recommendations for the use of second-generation polyvalent HPV vaccines. Our results also suggest that type-specific high-risk HPV-DNA-based screening tests and protocols should focus on HPV types 16, 18, and 45.

[Uterine and jejunum perforation due to intrauterine device. A report of a case and literature review]. / Perforación uterina y del yeyuno causada por un dispositivo intrauterino. Presentación de un caso con revisión de la literatura.

The application of a copper IUD can perforate completely the uterus and involve adjacent organs such as the bladder, small bowel, colon, rectum or appendix. Once the diagnosis is established, complete extraction must follow. We present a case report of a 33 year-old patient in which a copper IUD was placed in a medical office, three months after a third cesarean, without history of sepsis. Ninety days after placement, the patient complained of menstrual irregularities (opsomenhorrea) without any other symptoms. On physical examination with speculum, the IUD's guide strings were not visible; a transvaginal USG was performed without visualization of the IUD in the uterine cavity. An abdominal CAT scan showed the presence of the IUD outside the uterus. Hysteroscopy-laparoscopy was performed with transoperatory fluoroscopy, which revealed the copper IUD inside the yeyunum, a complete extraction followed with entero-entero anastomosis. This case will show that IUD placement is not innocuous and that adjacent organ damage must always be considered and resolved immediately.