RESUMEN
BACKGROUND: Human papillomavirus (HPV) testing on self-samples is a valid tool for cervical cancer screening. HPV self-sample workflows need to be clinically validated to ensure safe use in screening. OBJECTIVE: This study evaluated the fully automated NeuMoDx HPV Assay self-sample workflow that is compiled of the NeuMoDx HPV assay and the NeuMoDx 96/288 Molecular Systems, for clinical performance and reproducibility on Evalyn Brush-collected self-samples. METHODS: The clinical performance of the NeuMoDx HPV Assay self-sample workflow for cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and CIN3+ was evaluated on 987 self-samples obtained from women attending national organized HPV-based cervical cancer screening by a noninferiority analysis relative to reference workflows using either HPV-Risk Assay or high-risk HPV GP5+/6+-PCR. Intra- and inter-laboratory reproducibility of the NeuMoDx HPV Assay self-sample workflow using both NeuMoDx 96 and 288 Molecular Systems was assessed on 520 self-samples in three laboratories. RESULTS: The clinical sensitivity and specificity of the NeuMoDx HPV Assay self-sample workflow for the detection of CIN2+ and CIN3+ were found to be non-inferior to the reference workflows using either HPV-Risk Assay or high-risk HPV GP5+/6+-PCR, with all p-values <0.034. The NeuMoDx HPV Assay self-sample workflow exhibited an intra-laboratory reproducibility of 94.4 % (95 %CI:92.5-96.1 %) with kappa value 0.86 (95 %CI:0.81-0.91). Inter-laboratory agreement was high (all ≥93.4 % and all kappa values ≥0.83). CONCLUSIONS: The NeuMoDx HPV Assay self-sample workflow demonstrated high clinical accuracy for CIN2+/3+ and high reproducibility. The NeuMoDx HPV Assay self-sample workflow can be considered suitable for cervical cancer screening purposes.
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Infecciones por Papillomavirus , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Femenino , Humanos , Flujo de Trabajo , Infecciones por Papillomavirus/diagnóstico , Detección Precoz del Cáncer , Reproducibilidad de los Resultados , Papillomaviridae/genética , Displasia del Cuello del Útero/diagnóstico , Sensibilidad y EspecificidadRESUMEN
AIM: To assess the correlation between magnetic resonance imaging (MRI) and histopathology for predicting muscular infiltration of endometriosis in the bowel wall in patients undergoing colorectal resection. MATERIALS AND METHODS: All consecutive patients who underwent colorectal surgery for deep endometriosis (DE) with a preoperative MRI in a single tertiary care referral hospital between 2001 and 2019 were included in a prospective cohort. MRI images were revised by a single blinded radiologist. The MRI results regarding the infiltration depth (serosal, muscular, submucosal, or mucosal) and lesion expansion of DE were compared to histopathology. RESULTS: A total of 84 patients were eligible for evaluation. A sensitivity of 89% and positive predictive value of 97% was shown for predicting muscular involvement of the bowel wall. CONCLUSION: This study showed that MRI is valuable in predicting the involvement of the muscular layer of the colorectal wall. Therefore, in patients with symptomatic pelvic bowel endometriosis MRI is a useful tool in guiding the extent of colorectal surgery.
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Neoplasias Colorrectales , Endometriosis , Laparoscopía , Enfermedades del Recto , Femenino , Humanos , Endometriosis/diagnóstico por imagen , Endometriosis/cirugía , Endometriosis/patología , Estudios Prospectivos , Estudios Retrospectivos , Imagen por Resonancia Magnética/métodos , Neoplasias Colorrectales/cirugía , Laparoscopía/métodosRESUMEN
OBJECTIVES: The aim was to evaluate the cross-sectional and long-term triage performance of FAM19A4/miR124-2 methylation analysis in human papillomavirus (HPV)-based cervical screening. METHODS: We conducted a post hoc analysis within a Dutch population-based HPV-positive study cohort of women aged 30-60 years (n = 979). Cross-sectional cervical intraepithelial neoplasia (CIN) 3+ sensitivity, specificity, positive predictive value and negative predictive value as well as cumulative CIN3+ or cervical cancer risks after 9 and 14 years were compared for three baseline triage strategies: (1) cytology, (2) FAM19A4/miR124-2 methylation analysis and (3) combined FAM19A4/miR124-2 methylation with cytology. RESULTS: CIN3+ sensitivity of FAM19A4/miR124-2 methylation analysis was similar to that of cytology (71.3% vs 76.0%, ratio 0.94, 95% CI 0.84 to 1.05), at a lower specificity (78.3% vs 87.0%, ratio 0.90, 95% CI 0.86 to 0.94). Combining FAM19A4/miR124-2 methylation analysis with cytology resulted in a CIN3+ sensitivity of 84.6% (95% CI 78.3 to 90.8) at a specificity of 69.6% (95% CI 66.5 to 72.7). Similar 9- and 14-year CIN3+ risks for baseline cytology-negative women and baseline FAM19A4/miR124-2 methylation-negative women were observed, with risk differences of -0.42% (95% CI -2.1 to 1.4) and -0.07% (95% CI -1.9 to 1.9), respectively. The 14-year cumulative cervical cancer incidence was significantly lower for methylation-negative women compared to cytology-negative women (risk difference 0.98%, 95% CI 0.26 to 2.0). DISCUSSION: FAM19A4/miR124-2 methylation analysis has a good triage performance on baseline screening samples, with a cross-sectional CIN3+ sensitivity and long-term triage-negative CIN3+ risk equalling cytology triage. Therefore, FAM19A4/miR124-2 methylation analysis appears to be a good and objective alternative to cytology in triage scenarios in HPV-based cervical screening.
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Citocinas/genética , Infecciones por Papillomavirus/diagnóstico , Triaje/métodos , Adulto , Biomarcadores de Tumor/genética , Estudios Transversales , Metilación de ADN , Detección Precoz del Cáncer , Femenino , Humanos , Estudios Longitudinales , Tamizaje Masivo , MicroARNs/genética , Persona de Mediana Edad , Países Bajos/epidemiología , Papillomaviridae , Infecciones por Papillomavirus/genética , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/genética , Displasia del Cuello del Útero/diagnóstico , Displasia del Cuello del Útero/genéticaRESUMEN
BACKGROUND: Cervical cancer (CxCa) is mainly a locally invading disease that metastasizes to loco-regional lymph node basins before involving distant organs in more advanced stages. Local immune potentiation of tumor-draining lymph nodes (TDLN) may thus protect against tumor progression. METHODS: To identify therapeutic targets for local immune modulation, multi-parameter flow cytometric T-cell profiling of primary cervical tumors (PT) and TDLN (n = 37) was performed. The in-vitro effect of PD-1 blockade on T-cell reactivity to HPV16 E6 oncoproteins was determined in cultures of TDLN and PT single cell suspensions (n = 19). Also, intracellular cytokine staining (ICS) upon anti-CD3 stimulation was performed in metastatic TDLN (LN+) and PT (n = 7), as well as multiplexed immunofluorescence histochemistry staining (n = 8). RESULTS: Our data revealed elevated rates of activated regulatory T cells (aTregs) and of central or effector memory CD8+ T cells in metastatic TDLN (LN+) as compared to tumor-free TDLN (LN-), and equally high or even higher rates of these subsets in PT. Both memory subsets co-expressed multiple immune checkpoints. PD-1 blockade significantly enhanced detectable E6-specific T-cell responses in 4/5 HPV16+ LN+ and in 1/5 HPV16+ PT. Whereas aTreg rates were higher in anti-PD-1 non-responders, in responders elevated levels of CD8+FoxP3+CD25+ T cells were observed, which correlated with the efficacy of PD-1 blockade (P = 0.018). This subset was characterized by an early effector memory phenotype with particularly high levels of co-expressed PD-1, CTLA-4, TIM-3 and LAG-3 checkpoints, but, rather than exhausted, was shown upon polyclonal activation to produce higher levels of Granzyme-B and effector cytokines as compared to its CD8+FoxP3- counterparts. CONCLUSION: These observations support local PD-(L)1 blockade to interrupt loco-regional immune suppression in CxCa and control metastatic spread to TDLN. Furthermore, our data identify CD8+FoxP3+CD25+ T cells as therapeutic targets, which may also serve as predictive biomarker for PD-(L)1 checkpoint blockade.
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Antineoplásicos Inmunológicos/farmacología , Linfocitos T CD8-positivos/efectos de los fármacos , Nivolumab/farmacología , Receptor de Muerte Celular Programada 1/inmunología , Subgrupos de Linfocitos T/efectos de los fármacos , Neoplasias del Cuello Uterino/inmunología , Adulto , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Femenino , Humanos , Ganglios Linfáticos/inmunología , Persona de Mediana Edad , Proteínas Oncogénicas Virales/inmunología , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Proteínas Represoras/inmunología , Subgrupos de Linfocitos T/inmunologíaRESUMEN
UNLABELLED: Summary OBJECTIVE: Uterine serous carcinoma (USC) is an aggressive, histological subtype of endometrial cancer with a poor prognosis. This study evaluates the additional effect of staging surgery above total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH+BSO) on the use of adjuvant therapy and subsequent survival outcomes in clinical early-stage USC patients. MATERIALS AND METHODS: This retrospective cohort study includes 75 women treated for clinical early-stage USC. RESULTS: In 33 (44%) clinical early-stage patients surgical staging was performed and 15 patients (45%) proved to have lymphatic or abdominal metastasis. Use of adjuvant therapy was similar in patients, both staged with no metastasis (n = 18) and patients who underwent TAH and BSO only (n = 42, p = 0.17). No significant survival difference was found between surgically staged and TAH+BSO patients. CONCLUSIONS: Surgical staging proved to be important to determine stage of disease and hence prognosis. Surgical staging did not lead to selective avoidance of adjuvant therapy in patients with no metastasis.
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Quimioradioterapia Adyuvante/métodos , Quimioterapia Adyuvante/métodos , Neoplasias Endometriales/terapia , Histerectomía/métodos , Neoplasias Quísticas, Mucinosas y Serosas/terapia , Ovariectomía/métodos , Radioterapia Adyuvante/métodos , Salpingectomía/métodos , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Supervivencia sin Enfermedad , Neoplasias Endometriales/patología , Femenino , Humanos , Estimación de Kaplan-Meier , Escisión del Ganglio Linfático , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Quísticas, Mucinosas y Serosas/patología , Estudios Retrospectivos , Neoplasias Uterinas/patología , Neoplasias Uterinas/terapiaRESUMEN
BACKGROUND: Anyplex™ II HPV HR Detection (Seegene, Seoul, Korea) is a multiplex real-time PCR using tagging oligonucleotide cleavage and extension (TOCE) technology for simultaneous detection and genotyping of 14 high-risk (HR) HPV types, including HPV16 and HPV18. OBJECTIVES: To evaluate whether the clinical performance and reproducibility of Anyplex™ II HPV HR Detection meet the international consensus guidelines for HPV test requirements for cervical cancer screening [1]. STUDY DESIGN: The clinical performance of Anyplex™ II HPV HR Detection for detecting cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was determined relative to that of the reference assay, i.e., HR HPV GP5+/6+-PCR-EIA, by analysis of a total of 879 cervical liquid based cytology (LBC) specimens from a screening population, of which 60 were from women with CIN2+. The intra-laboratory reproducibility and inter-laboratory agreement were determined on 509 LBC samples, of which 172 were positive by the reference assay. RESULTS: Anyplex™ II HPV HR Detection showed a clinical sensitivity for CIN2+ of 98.3% (59/60; 95% CI: 89.1-99.8) and a clinical specificity for CIN2+ of 93.6% (764/816; 95% CI: 89.8-96.1). The clinical sensitivity and specificity were non-inferior to those of HR HPV GP5+/6+-PCR-EIA (non-inferiority score test: P=0.005 and P=0.023, respectively). Both intra-laboratory reproducibility (96.8%; 95% CI: 95.3-98.1; kappa value of 0.93) and inter-laboratory agreement (96.0%; 95% CI: 94.3-97.4; kappa value of 0.91) were high. CONCLUSIONS: Anyplex™ II HPV HR Detection performs clinically non-inferior to HR HPV GP5+/6+-PCR-EIA. Anyplex™ II HPV HR Detection complies with international consensus validation metrics for HPV DNA tests for cervical cancer screening [1].
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Alphapapillomavirus/aislamiento & purificación , Infecciones por Papillomavirus/diagnóstico , Displasia del Cuello del Útero/diagnóstico , Displasia del Cuello del Útero/prevención & control , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/prevención & control , Adulto , Alphapapillomavirus/genética , Colposcopía , Detección Precoz del Cáncer/métodos , Femenino , Genotipo , Humanos , Tamizaje Masivo , Persona de Mediana Edad , Infecciones por Papillomavirus/prevención & control , Infecciones por Papillomavirus/virología , Embarazo , Juego de Reactivos para Diagnóstico , Reacción en Cadena en Tiempo Real de la Polimerasa , Reproducibilidad de los Resultados , República de Corea , Sensibilidad y Especificidad , Neoplasias del Cuello Uterino/virología , Displasia del Cuello del Útero/virologíaRESUMEN
BACKGROUND: Women with borderline/mildly dyskaryotic (BMD) cytology smears are currently followed up with repeat testing at 6 and 18 months. The objective of this study is to analyse the cross-sectional and longitudinal performance of p16/Ki-67 dual-stained cytology for the detection of cervical intraepithelial neoplasia (CIN) grade 3 or worse (CIN3+) and CIN2+ in women with BMD, and to compare the results with baseline human papillomavirus (HPV) testing. METHODS: Conventional Pap cytology specimens of 256 women with BMD were dual stained for p16/Ki-67 retrospectively, and compared with baseline HPV results and long-term follow-up results. RESULTS: p16/Ki-67 dual-stained cytology showed a sensitivity of 100%, a specificity of 64.4% and a negative predictive value (NPV) of 100.% for CIN3+. Human papillomavirus testing demonstrated similar sensitivity (96.3%), and NPV (99.1%), but a significantly lower specificity (57.6%; P=0.024) for CIN3+. Sensitivity, specificity and NPV for CIN2+ of dual-stained cytology were 89.7%, 73.1% and 95.1%, respectively, which was similar when compared with HPV testing. Dual-stained cytology showed a significant lower referral rate than HPV testing (43.6% vs 49.1%; P=0.043). During long-term follow-up, no CIN3+ lesions developed in HPV-positive, dual-stained negative women. CONCLUSIONS: Comparable sensitivity and NPV of dual-stained cytology for CIN3+, combined with a significantly higher specificity, makes p16/Ki-67 dual-stained cytology a viable alternative to HPV testing for triaging BMD.
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Antígeno Ki-67/análisis , Proteínas de Neoplasias/análisis , Infecciones por Papillomavirus/diagnóstico , Displasia del Cuello del Útero/diagnóstico , Neoplasias del Cuello Uterino/diagnóstico , Adulto , Colposcopía/métodos , Estudios Transversales , Inhibidor p16 de la Quinasa Dependiente de Ciclina , Detección Precoz del Cáncer/métodos , Femenino , Humanos , Incidencia , Estudios Longitudinales , Persona de Mediana Edad , Prueba de Papanicolaou/métodos , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/virología , Estudios Retrospectivos , Factores de Riesgo , Coloración y Etiquetado/métodos , Resultado del Tratamiento , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/virología , Frotis Vaginal/métodos , Displasia del Cuello del Útero/patología , Displasia del Cuello del Útero/virologíaRESUMEN
In this report, we describe a case of a solely inhibin B producing fibrothecoma presenting with secondary amenorrhoea and hot flushes. Typical laboratory findings were an elevated LH, elevated inhibin B, low FSH and low estrogen. The World Health Organization classification of amenorrhoea was not applicable since the combination of low estrogen and low FSH suggested a central cause, whereas actually there was an ovarian cause. With staging laparotomy, a bilateral borderline tumour was detected in combination with a fibrothecoma. This report underpins the concept of inhibin B being a selective FSH secretion inhibitor of ovarian origin. Furthermore, a literature review on these topics is included.
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Amenorrea/complicaciones , Inhibinas/metabolismo , Neoplasias Ováricas/diagnóstico , Adulto , Biomarcadores de Tumor/metabolismo , Diagnóstico Diferencial , Estradiol/sangre , Femenino , Hormona Folículo Estimulante/sangre , Sofocos/complicaciones , Humanos , Inhibinas/sangre , Leiomioma/complicaciones , Leiomioma/diagnóstico por imagen , Hormona Luteinizante/sangre , Imagen por Resonancia Magnética , Neoplasias Ováricas/complicaciones , Neoplasias Ováricas/metabolismo , Ovario/diagnóstico por imagen , Ovario/patología , Tomografía Computarizada por Rayos X , Ultrasonografía , Útero/diagnóstico por imagen , Útero/patologíaRESUMEN
OBJECTIVE: Endometriosis infiltrating the bowel may be difficult to differentiate from colorectal carcinoma in cases that present with non-specific clinical and imaging features. The aim of this study is to assess the value of MR diffusion-weighted imaging (DWI) in differentiating endometriosis infiltrating the bowel from colorectal carcinoma. METHODS: In 66 patients, MR DWI was added to the standard imaging protocol in patients visiting our outdoor MR clinic for the analysis of suspected or known deep infiltrating endometriosis (DIE). In patients diagnosed with DIE infiltrating the bowel on MR imaging, high b-value diffusion-weighted images were qualitatively assessed by two readers in consensus and compared to high b-value diffusion weighted images in 15 patients evaluated for colorectal carcinoma. In addition, ADC values of lesions were calculated, using b-values of 50, 400 and 800 s/mm(2). RESULTS: A total of 15 patients were diagnosed with DIE infiltrating the bowel on MR imaging. Endometriosis infiltrating the bowel showed low signal intensity on high b-value diffusion-weighted images in all patients, whereas colorectal carcinoma showed high signal intensity on high b-value diffusion-weighted images in all patients. Mean ADC value in endometriosis infiltrating the bowel (0.80 ± 0.06 × 10(-3)mm(2)/s) was significantly lower compared to mean ADC value in colorectal carcinoma (0.86 ± 0.06 × 10(-3 )mm(2)/s), but with considerable overlap between ADC values. CONCLUSION: Only qualitative assessment of MR DWI may be valuable to facilitate differentiation between endometriosis infiltrating the bowel and colorectal carcinoma.
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Neoplasias Colorrectales/diagnóstico , Imagen de Difusión por Resonancia Magnética/métodos , Endometriosis/diagnóstico , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/patología , Diagnóstico Diferencial , Endometriosis/patología , Femenino , Humanos , Intestinos/patología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Estadísticas no ParamétricasRESUMEN
OBJECTIVE: Both the intraperitoneal seeding and the uterine-vesical extension theory have been proposed to explain the pathogenesis of bladder endometriosis. The aim of this study was to describe MR imaging findings of bladder endometriosis and involvement of the anterior uterine wall in a tertiary referral centre for endometriosis in a effort to improve diagnosis and help clarify the pathogenesis. METHODS: In a single-centre, retrospective study (2004-2009), 463 consecutive patients analysed for deep infiltrating endometriosis (DIE) were studied independently by two experienced readers for the presence of bladder endometriosis. MR studies revealing bladder endometriosis were then analysed in consensus for: location, size, signal intensity characteristics, uterine involvement, continuity with adenomyosis and presence of cysts. There was histopathologic correlation in 9 patients who had undergone partial bladder resection. RESULTS: Bladder endometriosis was diagnosed in 32 patients on MR imaging (k=0.85). Most lesions showed heterogeneous isointensity compared to that of muscle on T2-weighed imaging, containing foci of high signal intensity, suggesting cystic ectopic endometrial glands. On T1-weighted imaging lesions showed heterogeneous isointensity with foci or small cysts, demonstrating high signal intensity, indicating hemorrhage, was observed. Uterine involvement was found in 94% of the lesions, with either "continuous" or "hourglass" configurations. Presence of contiguous adenomyosis was found in only 4 lesions. CONCLUSIONS: With MR imaging, uterine involvement in bladder endometriosis is frequently found and in most cases located subserosally, suggesting extensive DIE, favouring the intraperitoneal seeding theory.
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Endometriosis/epidemiología , Endometriosis/patología , Imagen por Resonancia Magnética/estadística & datos numéricos , Enfermedades de la Vejiga Urinaria/epidemiología , Enfermedades de la Vejiga Urinaria/patología , Útero/patología , Adulto , Femenino , Humanos , Países Bajos/epidemiología , Prevalencia , Derivación y Consulta , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Centros de Atención Terciaria , Adulto JovenRESUMEN
OBJECTIVES: Penile cancer is a disease with a high morbidity and mortality. Its prevalence is relatively rare, but the highest in some developing countries. Insight into its precursor lesions, pathogenesis and risk factors offers options to prevent this potentially mutilating disease. This review presents an overview of the different histologically and clinically identified precursor lesions of penile cancer and discusses the molecular pathogenesis, including the role of HPV in penile cancer development. METHODS: A systematic review of the literature evaluating penile carcinogenesis, risk factors and molecular mechanisms involved. RESULTS: Careful monitoring of men with lichen sclerosis, genital Bowen's disease, erythroplasia of Queyrat and bowenoid papulosis seems useful, thereby offering early recognition of penile cancer and, subsequently, conservative therapeutic options. Special attention is given to flat penile lesions, which contain high numbers of HPV. Their role in HPV transmission to sexual partners is highlighted, but their potential to transform as a precursor lesion into penile cancer has been unsatisfactorily explored. CONCLUSIONS: Further research should not only focus on HPV mediated pathogenic pathways but also on the non-HPV related molecular and genetic factors that play a role in penile cancer development. Options for prevention of penile cancer include (neonatal) circumcision, limitation of penile HPV infections (either by prophylactic vaccination or condom use), prevention of phimosis, treatment of chronic inflammatory conditions, limiting PUVA treatment, smoking cessation and hygienic measures.
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Neoplasias del Pene , Humanos , Masculino , Neoplasias del Pene/clasificación , Neoplasias del Pene/diagnóstico , Neoplasias del Pene/epidemiología , Neoplasias del Pene/etiología , Neoplasias del Pene/prevención & controlRESUMEN
--Infection with high-risk genital Human papillomavirus (hrHPV) is necessary for the development of cervical cancer and its early stages. --Although it is widely accepted that infection with hrHPV is sexually transmitted, insight into the clinical manifestations of hrHPV infection in men is limited. --Flat penile lesions may be the hrHPV reservoir in men. --Their limited visibility with the naked eye explains why flat penile lesions may escape the attention of both the carrier and the clinician. The lesions can be visualized by the application of an acetic acid solution. They should be distinguished from papillary abnormalities occurring close to the frenulum and the pearl-shaped penile papulae around the coronary sulcus that do not accompany HPV. --Only flat penile lesions are associated with high numbers of HPV copies and therefore contribute to the sexual viral spread. --The use of condoms protects against sexual transmission of HPV.
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Infecciones por Papillomavirus/patología , Infecciones por Papillomavirus/transmisión , Pene/patología , Condones , Reservorios de Enfermedades/virología , Humanos , Masculino , Papillomaviridae/aislamiento & purificación , Carga ViralRESUMEN
We assessed clearance rates of 14 high-risk human papillomavirus (hrHPV) types in hrHPV-positive women with normal cytology and borderline/mild dyskaryosis (BMD) in a population-based cervical screening cohort of 44,102 women. The 6-month hrHPV type-specific clearance rates, that is, clearance of the same type as detected at baseline, in women with normal and BMD smears were 43% (95% confidence interval (CI) 39-47) and 29% (95% CI 24-34), respectively. Corresponding 18-month clearance rates were markedly higher, namely 65% (95% CI 60-69) and 41% (95% CI 36-47), respectively. The lowest clearance rates in women with normal cytology were observed for HPV16, HPV18, HPV31, and HPV33. Significantly reduced 18-month clearance rates at a significance level of 1% were observed for HPV16 (49%, 95% CI 41-59) and HPV31 (50%, 95% CI 39-63) in women with normal cytology, and for HPV16 (19%, 95% CI 12-29) in women with BMD. Among women who did not clear hrHPV, women with HPV16 persistence displayed an increased detection rate of >or=CIN3 (normal P<0.0001; BMD, P=0.005). The type-specific differences in clearance rates indicate the potential value of hrHPV genotyping in screening programs. Our data support close surveillance (i.e. referral directly, or within 6 months) of women with HPV16 and are inconclusive for surveillance of women with HPV18, HPV31, and HPV33. For the other hrHPV-positive women, it seems advisable to adopt a conservative management with a long waiting period, as hrHPV clearance is markedly higher after 18 months than after 6 months and the risk for >or=CIN3 is low.
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Alphapapillomavirus/aislamiento & purificación , Cuello del Útero/virología , Infecciones por Papillomavirus/diagnóstico , Neoplasias del Cuello Uterino/diagnóstico , Adulto , Cuello del Útero/patología , Femenino , Humanos , Tamizaje Masivo , Persona de Mediana Edad , Neoplasias del Cuello Uterino/virología , Frotis VaginalRESUMEN
We earlier demonstrated, in a randomised clinical trial, that the regression time of flat penile lesions in male sexual partners of women with cervical intraepithelial neoplasia (CIN) was shorter in men who used condoms compared to those who did not. To further evaluate this finding, we examined whether the effect of condom use on the regression of flat penile lesions depends on the presence of human papillomavirus (HPV) type concordance in sexual couples, as determined in cervical and penile scrapes by GP5+/6+ PCR testing. A Cox model with time-dependent covariates showed a beneficial effect of condoms on regression of flat penile lesions in concordant couples (hazard ratio 2.63, 95% CI 1.07-6.48) but not in those who were nonconcordant. When both partners harboured different HPV types, no effect of condoms was found (hazard ratio 0.90, 95% CI 0.27-2.96). Delayed regression of flat penile lesions was associated with either stable lesions or with new penile lesions developing at sites surrounding pre-existing lesions suggesting reinfection of the penile epithelium. We conclude that condom use blocks sexual HPV transmission by preventing reinfection and development of new penile lesions in men who are susceptible to the same type as present in the female partner.