Predictors of human papillomavirus infection in women undergoing routine cervical cancer screening in Spain: the CLEOPATRE study.

BACKGROUND: Human papillomavirus (HPV) is a sexually transmitted infection that may lead to development of precancerous and cancerous lesions of the cervix. The aim of the current study was to investigate socio-demographic, lifestyle, and medical factors for potential associations with cervical HPV infection in women undergoing cervical cancer screening in Spain. METHODS: The CLEOPATRE Spain study enrolled 3 261 women aged 18-65 years attending cervical cancer screening across the 17 Autonomous Communities. Liquid-based cervical samples underwent cytological examination and HPV testing. HPV positivity was determined using the Hybrid Capture II assay, and HPV genotyping was conducted using the INNO-LiPA HPV Genotyping Extra assay. Multivariate logistic regression was used to identify putative risk factors for HPV infection. RESULTS: A lifetime number of two or more sexual partners, young age (18-25 years), a history of genital warts, and unmarried status were the strongest independent risk factors for HPV infection of any type. Living in an urban community, country of birth other than Spain, low level of education, and current smoking status were also independent risk factors for HPV infection. A weak inverse association between condom use and HPV infection was observed. Unlike monogamous women, women with two or more lifetime sexual partners showed a lower risk of infection if their current partner was circumcised (P for interaction, 0.005) and a higher risk of infection if they were current smokers (P for interaction, 0.01). CONCLUSION: This is the first large-scale, country-wide study exploring risk factors for cervical HPV infection in Spain. The data strongly indicate that variables related to sexual behavior are the main risk factors for HPV infection. In addition, in non-monogamous women, circumcision of the partner is associated with a reduced risk and smoking with an increased risk of HPV infection.

Prevalence and genotype distribution of human papillomavirus infection of the cervix in Spain: the CLEOPATRE study.

Human papillomavirus (HPV) infection is a necessary cause of cervical cancer. The aim of this study was to estimate the prevalence of cervical HPV infection and HPV type-specific distribution among women attending cervical cancer screening in Spain during 2007 and 2008. Women aged 18-65 years were recruited according to an age-stratified sampling method. Liquid-based cervical samples were collected and analyzed for cytology, HPV detection, and genotyping. HPV genotyping was determined using the INNO-LiPA HPV Genotyping Extra Reverse Hybridization Line Probe Assay. Prevalence estimates were age-standardized using 2001 Spanish census data. The present study included 3,261 women. Age-standardized HC2-based HPV prevalence was 14.3% (95% CI, 13.1-15.5) among women aged 18-65 years, and 28.8% (26.6-31.1) among women aged 18-25 years. High-risk HPV types were detected in 12.2% (95% CI, 11.1-13.4) of HPV-tested women, representing 84.0% of HPV-positive samples. Multiple infections were present in 4.1% (95% CI, 3.4-4.8) of HPV-tested women (25.0% of HPV-positive samples). The most common high-risk HPV-types among HPV-tested women were 16 (2.9%), 52 (1.8%), 51 (1.6%), 31 (1.3%), and 66 (1.2%). HPV-type 16 was present in 16.9% of HPV-positive samples. One or more of the HPV vaccine types 6/11/16/18 were detected in 3.8% of HPV-tested women (22.1% of HPV-positive samples). Though not a true population-based survey, this study provides valuable baseline data for future assessment of the impact of current HPV vaccination programs in Spain. The high prevalence of HPV infection among young women may reflect recent changes in sexual behavior.

Polymorphism of the HLA-B*15 group of alleles is generated following 5 lineages of evolution.

Generation of the HLA-B*15 group of alleles has been analyzed using exon 1, intron 1, exon 2, intron 2, and exon 3 sequences from human and nonhuman primates. Results indicated that the 230 alleles analyzed could be grouped into 5 different lineages of evolution coming from nonhuman primate MHC-B* alleles sharing characteristic nucleotide sequences. The major evolutionary mechanism of evolution in this group of alleles is the gene conversion event with the exchange of genomic sequences present in other HLA-B*alleles. This evolutionary event reflects the importance of the exchanges between different genomic regions of distinct HLA-A*, -B*, or -C* alleles and only 1 group of HLA-B* alleles (B*15 in the present paper). These data also correlated with the geographic distribution of the lineages postulated and with the corresponding serologic specificities (B62, -63, -71, -72, -75, -76, and -77). In conclusion, the high degree of polymorphism of 1 group of alleles has a specific and simple pathway of evolution, which could result in new insight into the study of immune system functionality, disease association studies, and anthropological studies.

Platinum-based adjuvant chemotherapy on moderate- and high-risk stage I and II epithelian ovarian cancer patients. Long-term single institution experience and literature review.

BACKGROUND: Although the optimal management of women with FIGO stages I and II epithelial ovarian cancer (EOC) is still controversial, platinum-based adjuvant chemotherapy (CT) is the mainstay of treatment. Suboptimal survival results have led to major efforts to identify prognostic factors, improve surgical staging and develop adjuvant therapies to improve patients' outcomes. PATIENTS AND METHODS: We evaluate in a retrospective study clinical efficacy and the toxicity profile of a platinum-based adjuvant CT in FIGO stages I and II EOC treated at our institution from March 1984 to December 2006. Grade I FIGO stages IA-IB were excluded from the analysis. In the first period (1984-1997), patients received a platinum-based regimen without taxanes. In the second period from 1997 onwards, patients were treated with carboplatin and paclitaxel. Four to six cycles of adjuvant CT were administered. Potential predictive factors of efficacy and the role of paclitaxel addition were also analysed. RESULTS: One hundred and fifty-eight patients (60 treated with paclitaxel) met inclusion criteria and were evaluable. Median age at diagnosis was 53.7 years (range 19-81) and most patients had an Eastern Cooperative Oncology Group performance status score (ECOG) of 0-1 (91.8%); 82.9% patients had pathological stage I and 17.1% pathological stage II. With a median follow up of 8.34 years (range 4.4-11.6), 103 patients (74.1%) were free of disease and 110 of them were alive (79.1%). Median relapse-free survival (RFS) and median overall survival (OS) had not been reached at the time of the analysis. No survival difference was found between paclitaxel and carboplatin combination or non-paclitaxel-containing regimens. Statistically significant prognostic factors for better RFS in the multivariate analysis were: ECOG 0 (p=0.023; HR 0.32; 95% CI 0.17-0.57); FIGO I stage (p<0.001; HR 0.30; 95% CI 0.15-0.58); I-II histological grade (p=0.005; HR 0.38; 95% CI 0.19-0.75); mucinous histology (p=0.013; HR 0.28; 95% CI 0.13-0.53); non-surgical adherences (p<0.002, HR 0.32; 95% CI 0.15-0.54); paracolic gutters inspection (p=0.033; HR 0.50; 95% CI 0.26-0.95) and liver surface biopsies (p=0.048; HR 0.64; 95% CI 0.41-0.98).Toxicity was generally mild and non-haematologic events were the most commonly found (62.9% of the total). The most frequent haematologic toxicities were neutropenia (41.7% in all grades, 9.5% grade 3-4) and anaemia (29.1% in all grades, 3.2% grade 3-4). CONCLUSIONS: The long-term outcome of this series is comparable to the published evidence and reflects the limited activity of platinum-based CT in the adjuvant setting. The potential survival advantage of the addition of paclitaxel to carboplatin cannot be definitively answered due to the small number of patients, the limited follow-up and the retrospective nature of the study. More effective and specific treatments are clearly required, in particular for those patients with stage II and undifferentiated tumours. Quality of surgery entails prognostic value.

Human leukocyte antigen-G allele polymorphisms have evolved following three different evolutionary lineages based on intron sequences.

Human leukocyte antigen (HLA)-G alleles follow a different pattern of polymorphism generation from those of the HLA classical I alleles. These polymorphisms have been defined as a result of random permitted point mutations in exons. However, this polymorphism maintenance could have an evolutionary specific pathways based on noncoding regions as introns, 14-bp deletion/insertion (exon 8), or promoter regions. Therefore a systematic sequencing study of HLA-G alleles was done obtaining the complete genomic sequence of 16 different HLA-G alleles: nine alleles were intron and exon confirmatory sequences, four were exon confirmatory and new intron described sequences, and three were new alleles. A 14-bp deletion/insertion polymorphism was also sequenced in these alleles. These sequences, together with those previously published, were compared, and phylogenetic and molecular evolutionary analyses were performed. Results showed the presence of three major specific evolutionary patterns, tentatively named lineages, and the other four as minor lineages (only one allele). The relative age of the major lineages could also be established based on the number of lineage-specific positions and the number of alleles of each lineage. Two main mechanisms are clearly defined in the generation of the lineages (introns), gene conversion, and/or convergent evolution following specific patterns.

[Contasure Needleless: a single incision tot for the surgical treatment of stress urinary incontinence]. / Contasure needleless: TOT de una sola incision para el tratamiento de la incontinencia de urinaria de esfuerzo.

SUMMARY OBJECTIVES: The aim of this study is to describe the surgical technique, and assess the complications and middle-term results of the Contasure Needleless (Neomedic International), a single incision TOT sling for the surgical treatment of stress urinary incontinence. The main concept of this device is that it is not a mini-sling, it has 138% more surface area. We are analyzing the results of a minimally invasive solution that is a TOT like sling with the same known benefits of a TOT and the advantages of a single incision technique. The surface area to support the urethra of the Needleless is very similar to the surface area of the TOT. (16% less surface area of tissue ingrowths) It is 100% macroporous polypropylene without any additional material. METHODS: 120 patients were evaluated retrospectively. They were all treated of SUI with the Contasure Needleless.Female patients were evaluated under clinical study protocol consisting in cough test, urodynamic and Quality Of Life questionnaire, before and after the procedure. INCLUSION CRITERIA: patients with genuine SUI and patients with SUI plus concomitant procedures as prolapse. EXCLUSION CRITERIA: patients with ISD and or neurogenic incontinence. Anesthesia used: general (30%) or epidural (70%), patients with associated pathology. PROCEDURE: The 114 mm long and tension-free mesh was placed beneath the midurethra. The central part is 12 mm wide. The sling can be repositioned during surgery due to the 22 mm wide T-Pocket Positioning System located at the 2 edges. These pockets fixed the sling to the surrounding tissue in order to have the proper tissue in growth and anchoring. A 20mm sub urethral incision was made to dissect the paraurethral spaces only up to the ischiopubic ramus. A surgical forceps with the T-pocket folded was inserted into the dissected spaces and penetrates at the contra lateral side, like the standard transobturator technique. The forceps was introduced until the fascia of the Internal Obturator muscle was perforated. Then the forceps is opened to extend the pocket inside the muscle fibers for fixation. RESULTS: 120 patients with a mean age of 55 years (from 36 to 79) and a mean number of deliveries of 3 (0-7). Follow-up period: 24 months. SUCCESS RATE: 100 patients (84%) Improved rate: 10 patients (8%) Failure rate: 10 (8%) Mean operating time of sling procedure alone: 9 minutes (4-12). COMPLICATIONS: 3 patients had mesh extrusion solved with estrogens and 2 patients required short term catheterization due to voiding difficulties and no patients had inguinal pain. CONCLUSIONS: The results of the study suggest that the Contasure Needleless can be considered a minimally invasive TOT with no-needles and maintaining the same cure rate than our TOT cases at 2 years follow up.

Contasure Needleless: TOT de una sola incisión para el tratamiento de la incontinencia de urinaria de esfuerzo / Contasure needleless: a single incision TOT for the surgical treatment of stress urinary incontinence

OBJETIVO: El objetivo de este estudio es describir la técnica quirúrgica, medir la seguridad, resultados y posibles complicaciones a medio plazo de una técnica sin agujas Contasure Needleless (Neomedic International) un TOT de una sola incisión para el tratamiento quirúrgico de la incontinencia urinaria de esfuerzo.Un concepto básico de esta malla es que no es un Minislings, el Contasure Needleless es un TOT de una sola incisión posee una superficie de fibrosis 138% mayor que los minisling. Analizarémos el resultado de este procedimiento mínimamente invasivo. El área de soporte uretral del Contasure Needleless es muy similar al TOT (un 16% menor). El material es 100% polipropileno macro poroso.MÉTODO: 120 pacientes fueron evaluadas retrospectivamente. Todas las pacientes fueron operadas por incontinencia urinaria de esfuerzo con Contasure Needleless. El protocolo clínico que se siguió en todas estas pacientes fue test de esfuerzo, estudio urodinámico y cuestionario de calidad de vida antes y después del procedimiento. El criterio de inclusión fueron pacientes con incontinencia urinaria de esfuerzo en muchos casos con cirugía asociada. Pacientes con déficit intrínseco del esfínter o incontinencia neurógena fueron excluidas del estudio. La anestesia fue general en un 30% de las pacientes y epidural en un 70%.Se coloco una malla de polipropileno libre de tensión en la uretra media de 114 mm de largo (Contasure Needleless). La parte central la malla tiene 12mm ancho. La Malla puede ser ajustada durante la cirugía, posee dos bolsillos a cada lado. Estos bolsillos ayudan en un primer momento a mantener la malla y mas adelante proporcionaran un soporte a la malla debido a la fibrosis. Se hace una incisión suburetral de 20mm y se disecan los espacios parauretrales hasta la rama isquiopubica. Una Bengolea se introduce en los bolsillos y se cierra, después se inserta en los espacios disecados hasta penetrar el musculo obturador interno abriendo el bolsillo una vez penetrado el musculo, los mismos pasos se realizan en el lado contrario.RESULTADOS:120 pacientes con una edad media de 55 años (36 a 79) y una media de 3 partos (0-7). Seguimiento medio: 24 meses. De los 120 pacientes 100 de ellos (84%) están totalmente curados, Mejorados 10 pacientes (8%) y fracasos un 10 (8%). El tiempo medio de operación de colocación de la malla fue de 9 minutos (4-12). Complicaciones: 3 pacientes tuvieron una extrusión vaginal de la malla resuelta con estrógenos y 2 pacientes tuvieron dificultades temporales de vaciado, ningún paciente sufrió de dolor inguinal.CONCLUSIONES: Los resultados del estudio sugieren que el Contasure Needleless puede ser considerado un tratamiento de elección para tratamiento quirúrgico de la incontinencia urinaria de esfuerzo .Es un tratamiento mínimamente invasivo, sin el uso de agujas y mantiene resultados similares de curación a dos años de seguimiento que el TOT convencional (AU)

OBJECTIVES: The aim of this study is to describe the surgical technique, and assess the complications and middle-term results of the Contasure Needleless (Neomedic International), a single incision TOT sling for the surgical treatment of stress urinary incontinence.The main concept of this device is that it is not a mini-sling, it has 138% more surface area. We are analyzing the results of a minimally invasive solution that is a TOT like sling with the same known benefits of a TOT and the advantages of a single incision technique. The surface area to support the urethra of the Needleless is very similar to the surface area of the TOT. (16% less surface area of tissue ingrowths) It is 100% macroporous polypropylene without any additional material.METHODS: 120 patients were evaluated retrospectively. They were all treated of SUI with the Contasure Needleless. Female patients were evaluated under clinical study protocol consisting in cough test, urodynamic and Quality Of Life questionnaire, before and after the procedure. Inclusion criteria: patients with genuine SUI and patients with SUI plus concomitant procedures as prolapse. Exclusion criteria: patients with ISD and or neurogenic incontinence. Anesthesia used: general (30%) or epidural (70%), patients with associated pathology(AU)

PROCEDURE: The 114 mm long and tension-free mesh was placed beneath the midurethra. The central part is 12mm wide. The sling can be repositioned during surgery due to the 22mm wide T-Pocket Positioning System located at the 2 edges. These pockets fixed the sling to the surrounding tissue in order to have the proper tissue in growth and anchoring. A 20mm sub urethral incision was made to dissect the paraurethral spaces only up to the ischiopubic ramus. A surgical forceps with the T-pocket folded was inserted into the dissected spaces and penetrates at the contra lateral side, like the standard transobturator technique. The forceps was introduced until the fascia of the Internal Obturator muscle was perforated. Then the forceps is opened to extend the pocket inside the muscle fibers for fixation.RESULTS: 120 patients with a mean age of 55 years (from 36 to 79) and a mean number of deliveries of 3 (0-7). Follow-up period: 24 months. Success rate: 100 patients (84%) Improved rate: 10 patients (8%) Failure rate: 10 (8%) Mean operating time of sling procedure alone: 9 minutes (4-12).Complications: 3 patients had mesh extrusion solved with estrogens and 2 patients required short term catheterization due to voiding difficulties and no patients had inguinal pain.CONCLUSIONS: The results of the study suggest that the Contasure Needleless can be considered a minimally invasive TOT with no-needles and maintaining the same cure rate than our TOT cases at 2 years follow up(AU)

Vacuna frente al virus del papiloma humano y cribado de cáncer de cuello de útero / Human papilloma virus vaccine and screening for cervical cancer

La vacunación frente al virus del papiloma humano (VPH) es una estrategia preventiva primaria altamente eficaz y segura contra el cáncer de cuello de útero, pero no elimina la necesidad de seguir aplicando a las mujeres vacunadas un programa de prevención secundaria. El uso clínico de la vacuna determinará un número apreciablemente menor de resultados citológicos anormales, expresión de la alta eficacia de la vacunación frente a la infección incidente por VPH. En consecuencia, se deberá usar una prueba muy sensible en primera línea del cribado en sustitución de la citología, con problemas de sensibilidad. La prueba de determinación del VPH es muy sensible, y cuando se usa en el grupo de edad adecuado (> 30 años) es muy específico. El uso sinérgico de vacunación y cribado rediseñado se ha mostrado en los modelos de evaluación publicados como una estrategia altamente eficaz y muy eficiente (AU)

The HPV vaccine is a primary preventive strategy against cervical cancer. It is highly effective and safe, but its implementation does not preclude the need to maintain a secondary prevention protocol for all vaccinated women. The clinical use of the vaccine will lead to a noticeably lower number of abnormal smear reports, as a result of the vaccine¿s high efficacy against the HPV infection. Consequently, a higher sensitivity test needs to be applied as a first-line screening test, instead of Pap smears, with lower sensitivity. The HPV test is highly sensitive, and when applied to the appropriate age group (30+), it is also very specific. In the published evaluation models, the combined use of the vaccine and the redesigned screening test has been proved to offer high levels of efficacy and efficiency (AU)

Carcinoma invasor de la mama: estadificación molecular del ganglio centinela / Breast invasive carcinoma: the molecular stratification of sentinel node

Demostrar que existe un grupo de pacientes estadios patológicos N0 que presentan metástasis en el estudio del ganglio centinela no diagnosticados por métodos de rutina. El estudio del análisis molecular nos informa o no sobre el pronóstico, y podría considerarse como factor independiente. Se observó una relación agrupando los casos de mayor riesgo conocido, detectándose una población de bajo riesgo en la que se obviaría la quimioterapia. Observamos, que si agrupamos las pacientes con Ki-67 mayor de 5 por ciento, la mayoría de los casos en las que se observaron micro metástasis estaban en este grupo; aceptamos una relación entre los dos factores pronóstico. Algo similar sucede con pacientes grado II y III; la relación con la existencia de micrometástasis es evidente, pudiendo aceptarse que existe un grupo de carcinomas de mama de menor agresividad; se plantea que estas pacientes no reciban tratamiento adyuvante, y no planificar tratamientos quirúrgicos agresivos.

Demonstrated that exist a group of patients with pathological stage No who present metastases in the study of sentinel nodule no diagnostic for routine method. The study of molecular analysis inform or not about the prognosis and be considered a prognosis independent factor. We observed a relation between the mayor risk known cases and detected a low risk population in which obviated the chemotherapy. We observed that grouped patients with Ki-67 raised of 5 % the majority of the cases in which observed micro metastases were in these group; we accepted a relationship between this two prognosis factors. Some similar occur with patient’s grade II and grade III; the relation with the existence of micro metastases is evident, and we accepted that exist a group of breast carcinoma of less aggressive; for these reason we planted that these patient does not receive adjuvant treatment, and no planned surgical aggressive treatment.

Overexpression of SPARC protein contrasts with its transcriptional silencing by aberrant hypermethylation of SPARC CpG-rich region in endometrial carcinoma.

Secreted protein acidic and rich in cysteine (SPARC) is a secreted matricellular glycoprotein involved in crucial processes that occur during cancer. This study explored the occurrence of deregulated expression of SPARC in endometrial carcinomas, since it has been associated with the progression of other tumor types. We analyzed the expression of SPARC in endometrial carcinomas by TaqMan, Western blotting and immunohistochemistry. The CpG island methylation status of SPARC was evaluated by bisulfite sequencing method. A significant down-regulation of SPARC mRNA expression (p<0.001) was observed in endometrial tumor tissues, regardless of their microsatellite instability status (MSI). The down-regulation can be accounted for by aberrant hypermethylation of its CpG-rich region, since we demonstrate that SPARC is a frequent target of this epigenetic event in this pathology. Although, differential expression of SPARC is already known in other cancer types, we report that down-regulation of the SPARC gene in endometrial tumors, formed by at least 80% of epithelial tumor cells, contrasts with a frequent overexpression of SPARC protein, with strong immunoreactivity in stromal cells. These results indicate a cell type specific expression of SPARC in endometrial carcinomas. Accumulation of SPARC protein in most tumors compared to normal tissues (p<0.025), suggests an important role in the carcinogenesis of endometrial tumors. SPARC overexpression can be a useful molecular tool that may contribute to the diagnosis of this disease.

Results of the national survey of borderline ovarian tumors in Spain.

MATERIAL AND METHODS: Retrospective multi-center analysis of women diagnosed with borderline ovarian tumor and treated between January 1990 and December 1997. A national survey was conducted, in which 457 patients from 27 centers corresponding to ten of Spain's autonomous communities were analyzed. RESULTS: Four hundred fifty-seven women with borderline ovarian tumor were analyzed. The mean age of patients was 45.5+/-16.9 years. Of these, 390 patients (85.3%) were at stage I, 8 (1.8%) were at stage II and 36 (7.9%) at stage III. A bilateral tumor was observed in 63 women (13.8%). The mean tumor size was 14.2 cm and in 88 cases (19.3%) the tumor was on the surface of the ovary. Microinvasion was observed in 25 (5.5%) cases, and 29 women (6.3%) showed a micropapillary pattern. Study of the factors related to the appearance of peritoneal implants revealed positive tumor markers (OR 15.02: 1.9-32.9) and a tumor on the ovarian surface (OR 8.0: 1.8-127) to be independent risk factors. With respect to recurrence, the presence of peritoneal implants at the time of initial surgery (OR 3.4: 1.1-10.4) and signs of microinvasion in the anatomicopathological study (OR 5.5: 1.5-17.8) were found to be independent risk factors. The overall survival rate in our series was 97% with a mean follow-up of 88.3 months. The survival rate by stage was 97% for stage I, 100% for stage II and 97% for stage III. CONCLUSIONS: Although borderline ovarian tumors have an excellent prognosis, they are not exempt from a risk of recurrence. Characterization of patients with borderline ovarian tumor is essential in order to prevent their evolution. Likewise, the taking on board of risk factors will enable more selective treatments to be offered in each case.

Infección por el virus del papiloma humano (VPH) / No disponible

No disponible