HPV vaccination coverage in women between 15 and 55 years old in Spain: Temporal trend during the period 2007-2020.

OBJECTIVE: The objective of this study was to analyse the temporal trend of HPV vaccination coverage (VC) in Spain in women aged 15-55 years not included in systematic vaccination programmes during the period 2007-2020. METHODS: We assessed the vaccine coverage rate in this population based on three estimations: 1) annual vaccination coverage with at least one dose (VCR ≥ 1d), 2) annual VC for the full schedule (VCR3d), and 3) cumulative VC for the full schedule (aVCR). RESULTS: Annual VCR ≥ 1d and VCR3d were highest in 2008 (2.40% and 0.66% respectively) and subsequently decreased drastically in 2011 (0.55% and 0.15%). From 2017 to 2019 there was an increase from 1.4-fold to 1.6-fold, respectively, which decreased in 2020. In relation to aVCR, there was an increasing trend throughout the study period with approximately 4.03% of the study population having been vaccinated against HPV in 2020. CONCLUSION: In Spain, the cumulative vaccination coverage against HPV in women between 15-55 years old not included in current vaccination programmes remains very low. Nonetheless, the temporal trend has shown a slight increase in recent years. Despite the COVID-19 pandemic in 2020, no significant negative impact on vaccination coverage has been observed in this population.

Use of the Robson Classification System to Assess Cesarean Delivery Rate in a Tertiary Hospital in the Basque Country.

OBJECTIVES: To assess the rate of cesarean delivery at Basurto University Hospital (Bilbao, Spain) between 2015 and 2017 and to determine the cause of an increase in this rate during 2017. METHODS: We retrospectively reviewed 6975 deliveries between 2015 and 2017, classifying women using the Robson classification. We analyzed extended perinatal mortality and perinatal outcomes during the study period and performed a comparative analysis of cesarean deliveries by year and Robson group. Comparisons were made with analysis of variance and χ2 or Fisher's exact tests. RESULTS: During the study period, 928 cesarean deliveries (13.3%) were performed. Extended perinatal mortality in this period was 7.0%. We detected an increase in the rate of cesarean delivery in 2017 in Group 1 women (P = 0.0224), with significant differences in the homogeneity of the distribution of cesarean deliveries performed for fetal distress between years in this group (P = 0.0093). Auditing the cases of cesareans performed for fetal distress in Group 1 in 2017, we found that the indication was appropriate in all cases, but in 39.4%, the management of uterine contractions during labour was considered suboptimal. CONCLUSION: Classifying cesarean deliveries using the Robson classification allows us to compare cesarean rates in different years and analyze any increases in these rates. Increases are sometimes attributed to changes in the obstetric population, but when investigated may be found to be related to potentially correctable problems. It is not necessary to have a high rate of cesarean delivery to warrant internal audit.

Arteriovenous Malformation of the Cervical Spine Presenting as Subarachnoid Hemorrhage.

Arteriovenous malformations (AVM) of the cervical spine can present with symptoms resulting from their mass effect, vascular steal, or subarachnoid hemorrhage (SAH). While ruptured cerebral aneurysms bleed fast and usually cause severe headache, AVM bleed slowly; moreover, when the location is extracranial, the presentation might be even more confusing. For these reasons, the clinical course can be misleading. We present the case of a woman who had bleeding from an AVM of the cervical spine and discuss the classification and treatment options of AVM.

RNA extraction method is crucial for human papillomavirus E6/E7 oncogenes detection.

BACKGROUND: Human papillomavirus (HPV) DNA testing plays a main role in the management of cervical cancer, however to improve the specificity in cervical screening, there is a need to develop and validate different approaches that can identify women at risk for progressive disease. Nowadays, mRNA expression of viral E6 and E7 HPV oncogenes stands up as a potential biomarker to improve cervical screening. We aimed to validate a method for RNA extraction, detect HPV mRNA expression and, assess the relationship between E6/E7 mRNA expression and pathology of patients' lesions and progression. METHODS: This study included 50 specimens that had been previously genotyped as HPV16, 18, 31, 33 and/or 45. Cervical swabs were extracted with three different RNA extraction methods -Nuclisens manual extraction kit (bioMérieux), High Pure Viral RNA Kit (Roche) and RNeasy Plus Mini kit (Qiagen)-, and mRNA was detected with NucliSens EasyQ HPV version 1 test (bioMérieux) afterwards. Association of oncogene expression with pathology and lesion progression was analyzed for each extraction method. RESULTS: E6/E7 mRNA positivity rate was higher in samples analyzed with bioMérieux (62%), followed by Roche (24%) and Qiagen (6%). Women with lesions and lesion progression showed a higher prevalence of viral RNA expression than women that had not lesions or with lesion persistence. While bioMérieux revealed a higher sensitivity (77.27%), Roche presented a higher PPV (75%) and an increased specificity (89.28%). CONCLUSIONS: Extraction methods based on magnetic beads provided better RNA yield than those based in columns. Both Nuclisens manual extraction kit (bioMérieux) and High Pure Viral RNA Kit (Roche) seemed to be adequate for E6/E7 mRNA detection. However, none of them revealed both high sensitivity and specificity values. Further studies are needed to obtain and validate a standard gold method for RNA expression detection, to be included as part of the routine cervical screening program.

Assessment of human papillomavirus E6/E7 oncogene expression as cervical disease biomarker.

BACKGROUND: The aims of this study were to detect HPV E6/E7 mRNA expression in women with high-risk genotypes (HPV-16, -18, -31, -33 and -45) analysing its relationship with tissue pathology and 2) 2-year follow-up of E6/E7 mRNA tested group. METHODS: Our samples were genotyped and classified by pathologists according to Bethesda system. After RNA extraction, E6/E7 oncogene mRNA detection was performed by NucliSens® EasyQ® HPV v1 Test (bioMérieux). RESULTS: The results of the present study showed that E6/E7 mRNA positivity rate was 68.29 % in women tested once and 69.56 % in women tested twice. According to tissue pathology, all samples with high-grade lesions were positive for mRNA. Among women with low-grade lesions varied over the years from 89.28 to 84 % in women tested once and from 77.77 to 70 % in tested twice. Among women without lesion, positivity rate maintained in women tested once (from 50 to 41.38 %) and decreased in tested twice, from 63.63 to 44.44 %. Regarding lesion evolution, mRNA positivity was higher in women with lesion progression (53.13 %) and in women with positive results in two tested samples (83.33 %). CONCLUSION: HPV E6/E7 mRNA detection may be an effective screening test and biomarker for cervical cancer in women infected with these five genotypes. Nonetheless, further studies are needed to standardize as routine triage test.

Abordaje multidisciplinar de la infección por virus del papiloma humano / Multidisciplinary approach to human papillomavirus infection

No disponible

Human Papillomavirus 16 Variants May Be Identified by E6 Gene Analysis.

AIMS: The aims of the study were (1) to characterize the genetic variability of human papillomavirus (HPV) genotype 16 in the E6 region when this genotype is present in multiple infection samples, (2) to assess the prevalence of variants in our region and (3) to analyze the relationship between variants, patients' ages and pathology. METHODS: The Clinical Microbiology and Infection Control Department analyzed samples which were positive for genotype 16 and other genotypes from 2007 to 2013. Variants were assigned to European, Euro-German, Asian, Asian-American or African lineage by sequence analysis. The relationship among variants, age and different types of lesion was studied. RESULTS: In HPV-16 sequence analysis, the European variant was detected in 85.10% of samples, the Asian-American in 7.80%, the African in 4.25% and the Euro-German in 2.83% of specimens. Sequence genetic variability showed 16 nucleotide substitutions. Moreover, non-European variants were mainly found in old women and in isolates from high-grade squamous intraepithelial lesions since European variants were mainly detected in negative cytologies. CONCLUSION: Multiple infections may take effect on nucleotide substitution and the appearance of recombinant samples. Single gene analysis makes it impossible to detect recombination which has a great influence on drug response and vaccine strategies. Thus, E6 gene analysis would be enough to identify HPV-16 intratypic variants but not to confirm the results.

Situación de las unidades de patología cervical en España. Resultados de una encuesta nacional / Cervical pathology units in Spain today. Results of a national survey

Objetivos. Conocer el grado de implementación de las Unidades de Patología Cervical (UPC) en los hospitales españoles. Describir su organización asistencial y volumen de trabajo, así como sus necesidades formativas, de protocolización y control de calidad, como base para la elaboración de un proyecto conjunto de la Sociedad Española de Ginecología y Obstetricia (SEGO) y la Asociación Española de Patología Cervical y Colposcopia (AEPCC) de Acreditación de UPC. Material y métodos. Análisis descriptivo de los resultados de una encuesta dirigida a los Servicios de Ginecología de los hospitales españoles, entre noviembre del 2012 y enero del 2013. De las 220 encuestas enviadas, se obtuvo respuesta en 128 (58%), representando a todas las comunidades autónomas españolas. Resultados. El 70% de los hospitales encuestados disponen de UPC. La media de ginecólogos que trabajan a tiempo completo en la UPC es de 3 y a tiempo parcial, de 20. El promedio de actividad anual reportada fue de 178 nuevos diagnósticos, 79 casos de neoplasia intraepitelial de cérvix 2 positivas y 87 cirugías de conización cervical. El 60% de los hospitales disponen de registros de complicaciones y de correlaciones citológicas, colposcópicas e histológicas. Un 90% sigue las recomendaciones de AEPCC y SEGO para la prevención primaria y secundaria del cáncer de cérvix. Más del 90% de los médicos consultados considerarían adecuado que la AEPCC y la SEGO promoviesen la acreditación de las UPC. Conclusiones. La situación global de las UPC en España es buena pero mejorable en algunos aspectos. La mayoría de los centros ven adecuada la existencia de una acreditación para las UPC (AU)

Objectives. To determine the extent to which Cervical Pathology Units (CPU) are implemented in Spanish hospitals and to describe their organization and workload and requirements for training, standardization, and quality assurance, as a basis for a joint project of the Spanish Society of Obstetrics and Gynecology (SEGO) and the Spanish Association of Cervical Pathology and Colposcopy (AEPCC) for CPU accreditation. Material and methods. We performed a descriptive analysis of the results of a survey of Gynecology Services at Spanish hospitals between November 2012 and January 2013. A total of 220 surveys were sent and replies were received from 128 services (58%) representing all the Spanish regions. Results. A total of 70% of the hospitals in the survey had a CPU. There was an average of 3 full-time gynecologists and 20 part-time gynecologists at each CPU. The mean annual reported activity was 178 new cases, 79 cervical intraepithelial lesions 2 positive, and 87 conizations. Sixty percent of the hospitals had a register of complications and cytological, colposcopic and histological correlations. Ninety percent followed the recommendations of the AEPCC and the SEGO for primary and secondary prevention of cervical cancer. More than 90% of the gynecologists believed it would be appropriate for the AEPCC and the SEGO to promote CPU accreditation. Conclusions. The overall situation of CPU in Spain is good but could be improved. Most hospitals in the survey believe that implementing the accreditation process would not be difficult (AU)

Human papillomavirus (HPV) genotype 18 variants in patients with clinical manifestations of HPV related infections in Bilbao, Spain.

BACKGROUND: Human papillomavirus (HPV) variants differ in their biological and chemical properties, and therefore, may present differences in pathogenicity. Most authors classified variants based on the phylogenetic analysis of L1 region. Nevertheless, recombination in HPV samples is becoming a usual finding and thus, characterizing genetic variability in other regions should be essential. OBJECTIVES: We aimed to characterize the genetic variability of HPV 18 in 5 genomic regions: E6, E7, E4, L1 and the Upstream Regulatory Region (URR), working with both single infection and multiple HPV infection samples. Furthermore, we aimed to assess the prevalence of HPV 18 variants in our region and look for possible existence of recombination as well as analyze the relationship between these variants and the type of lesion. METHODS: From 2007 to 2010, Clinical Microbiology and Infection Control Department analyzed 44 samples which were positive for HPV 18. Genetic variability was determined in PCR products and variants were assigned to European, Asian-amerindian or African lineage. Recombination and association of variants with different types of lesion was studied. RESULTS: Genetic analysis of the regions revealed a total of 56 nucleotide variations. European, African and Asian-amerindian variants were found in 25/44 (56.8%), 10/44 (22.7%) and 5/44 (11.4%) samples, respectively. We detected the presence of recombinant variants in 2/44 (4.5%) cases. Samples taken from high-grade squamous intraepithelial lesions (H-SIL) only presented variants with specific-african substitutions. CONCLUSIONS: Multiple HPV infection, non-european HPV variants prevalence and existence of recombination are considered risk factors for HPV persistence and progression of intraepithelial abnormalities, and therefore, should be taken into consideration in order to help to design and optimize diagnostics protocols as well as improve epidemiologic studies.Our study is one of the few studies in Spain which analyses the genetic variability of HPV18 and we showed the importance of characterizing more than one genomic region in order to detect recombination and classify HPV variants properly.

Pregnancy outcome in patients treated with cervical conization for cervical intraepithelial neoplasia.

OBJECTIVE: To examine the causal contribution of conization to premature delivery. METHODS: This was a retrospective, case-control, multicenter study of women who underwent conization in 5 hospitals in the Basque Country (Spain) from 1998 to 2007. Three study groups were established: group A, post-conization infant deliveries; control group B, pre-conization infant deliveries; and control group C, infant deliveries without conization. RESULTS: Comparing group A with group C, there was a higher rate of preterm delivery before 35 weeks (5.3% versus 1.6%), a lower mean birth weight (3156.2g versus 3328.5 g), and a greater prevalence of infants under 2500 g (10.6% versus 3.7%). There were no significant differences between group A and group B: preterm delivery before 35 weeks (5.3% versus 4.8%), mean birth weight (3156.2g versus 3119.4 g), and prevalence of infants under 2500 g (10.6% versus 10.6%). CONCLUSION: Pregnancy in women post-conization was associated with a risk of preterm delivery. However, there were no significant differences between women who underwent conization before and those who underwent conization after delivery. Cervical conization does not necessarily increase the risk of preterm delivery in subsequent pregnancy. Conization should be considered an indicator of such risk because it is associated with pregnancy complications arising from socio-epidemiologic factors present in women requiring conization that are also present in women who have premature delivery.

Situación de la conización del cuello uterino en el País Vasco / Conization in the Basque Country (Spain)

Objetivos: El objetivo principal del estudio es determinar cuál es la técnica empleada en el País Vasco para practicar la conización del cuello del útero, así como el lugar más adecuado para practicar una conización (en consulta o en el quirófano), tomando como parámetro la tolerancia al dolor de la paciente, la incidencia de complicaciones inmediatas y tardías, y los resultados anatomo patológicos de los dos procedimientos. Material y métodos: Se seleccionó a 232 pacientes con un diagnóstico citológico y colposcópico de displasia cervical, que debieran estudiarse y/o tratarse mediante un procedimiento excisional del cuello uterino durante el período comprendido entre el 1 de septiembre de 2006 y el 31 de julio de 2007 en 8 hospitales del País Vasco. Resultados: El 94,8% de las conizaciones se hicieron con asa de diatermia en todos los hospitales y, excepcionalmente, con bisturí. La anestesia utilizada fue local en los hospitales terciarios y regional en los hospitales comarcales. La tolerancia al dolor en las conizaciones ambulatorias realizadas con asa de diatermia bajo anestesia local fue excelente. En el Hospital Donostia se puntuó el dolor con una escala analógica visual, logrando puntuaciones bajas concordantes con la alta satisfacción del procedimiento. La afectación de los bordes de la pieza de conización depende del grado de displasia y no de la técnica utilizada. Las complicaciones inmediatas fueron pocas, y fueron incluso menores las tardías (AU)

Objective: The main objective of this study was to evaluate the conization technique used in Basque Country hospitals and to determinate the most appropriate place to perform this procedure (outpatient clinic or operating room) by evaluating pain, early and late complications and histological results. Materials and methods: We selected 232 patients with a cytologic and colposcopic diagnosis of cervical dysplasia requiring surgical cervical conization between September 2006 and July 2007 in eight public hospitals of the Basque Country. Results: A total of 94.8% of conizations were performed with long loop excision of transformation zone (LLETZ) and, exceptionally, with cold knife conization. Local anesthesia was used in tertiary hospitals and regional anesthesia in county hospitals. Pain tolerance in outpatient conization with LLETZ under local anesthesia was excellent. In Hospital Donostia, pain was scored on a visual analogue scale and low scores were achieved, in accordance with the high degree of satisfaction obtained with the procedure. Conization margins depended on the grade of dysplasia rather than on the technique. There were few early complications and even fewer late complications. Conclusion: The LLETZ method performed under local anesthesia in the outpatient clinic is very well tolerated by patients and has few complications. Consequently, this option is a valid alternative to conization under general or regional anesthesia. The LLETZ technique provides multiple advantages for the patient and health service due to its lower cost, without medical disadvantages, and satisfactory tolerance (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)