RESUMEN
This study demonstrates that both the clinical sensitivity and specificity of the Cervista HPV HR test for high-risk human papillomavirus (HPV) detection are not inferior to those of the Hybrid Capture 2 (HC2) test. The intra- and interlaboratory reproducibilities of Cervista were 92.0% (kappa, 0.83) and 90.4% (kappa, 0.80), respectively. The Cervista HPV HR test fulfills all the international HPV test requirements for cervical primary screening purposes.
Asunto(s)
Tamizaje Masivo/métodos , Técnicas de Diagnóstico Molecular/métodos , Papillomaviridae/aislamiento & purificación , Neoplasias del Cuello Uterino/diagnóstico , Adulto , Femenino , Humanos , Persona de Mediana Edad , Papillomaviridae/genética , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Neoplasias del Cuello Uterino/virologíaRESUMEN
OBJECTIVE: The aim of this study was to determine possible impact of routinely scheduled biopsies and more radical surgery for residual central disease in locally advanced cervical cancer after (chemo)radiation. METHODS/MATERIALS: Data were analyzed of a consecutive series of cervical cancer patients (The International Federation of Gynecology and Obstetrics stages IB1-IVA) treated with (chemo) radiation between 1994 and 2011. Patients underwent gynecologic examination with biopsies 8 to 10 weeks after treatment. Since 2001, larger biopsies by electric loop excision were taken, and more radical surgery (type III hysterectomy or exenteration) was performed for central residual disease. Primary outcome was locoregional recurrence. Secondary outcomes were treatment-associated morbidity and disease-specific survival. RESULTS: Primary (chemo)radiation was given to 491 cervical cancer patients; 345 patients had a posttreatment biopsy. Viable tumor cells were identified in 84 patients, and 61 patients were eligible for salvage surgery. Residual disease after (chemo)radiation was an independent poor prognostic factor (hazard ratio, 3.59; 95% confidence interval, 2.18-5.93; P < 0.001). After 2001, larger biopsies were more frequently taken (29% vs 76%, P < 0.001), and in patients without viable tumor cells, locoregional recurrence after 2001 decreased from 21% to 10% (P = 0.01). After 2001, more patients underwent more radical surgery (46% vs 90%) (P < 0.001). Locoregional recurrence after surgery before 2001 occurred in 6 (46%) of the 13 patients, comparable with 19 (40%) of the 48 (P = 0.67) after 2001. More radical surgery was not associated with improved disease-specific survival (HR, 0.84; 95% CI, 0.20-3.46; P = 0.81) but did result in significantly more severe morbidity. CONCLUSION: More radical surgery in patients with (minimal) central residual disease identified by routine biopsy 8 to 10 weeks after (chemo)radiation does not improve survival and should not be recommended.
Asunto(s)
Carcinoma de Células Escamosas/terapia , Quimioradioterapia , Histerectomía/métodos , Recurrencia Local de Neoplasia/cirugía , Terapia Recuperativa/métodos , Neoplasias del Cuello Uterino/terapia , Adulto , Anciano , Carcinoma de Células Escamosas/epidemiología , Carcinoma de Células Escamosas/patología , Supervivencia sin Enfermedad , Femenino , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/patología , Neoplasia Residual , Complicaciones Posoperatorias/epidemiología , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/patologíaRESUMEN
BACKGROUND: Cytology-based screening methods for cervical adenocarcinoma (ADC) and to a lesser extent squamous-cell carcinoma (SCC) suffer from low sensitivity. DNA hypermethylation analysis in cervical scrapings may improve detection of SCC, but few methylation markers have been described for ADC. We aimed to identify novel methylation markers for the early detection of both ADC and SCC. RESULTS: Genome-wide methylation profiling for 20 normal cervices, 6 ADC and 6 SCC using MethylCap-seq yielded 53 candidate regions hypermethylated in both ADC and SCC. Verification and independent validation of the 15 most significant regions revealed 5 markers with differential methylation between 17 normals and 13 cancers. Quantitative methylation-specific PCR on cervical cancer scrapings resulted in detection rates ranging between 80% and 92% while between 94% and 99% of control scrapings tested negative. Four markers (SLC6A5, SOX1, SOX14 and TBX20) detected ADC and SCC with similar sensitivity. In scrapings from women referred with an abnormal smear (n=229), CIN3+ sensitivity was between 36% and 71%, while between 71% and 93% of adenocarcinoma in situ (AdCIS) were detected; and CIN0/1 specificity was between 88% and 98%. Compared to hrHPV, the combination SOX1/SOX14 showed a similar CIN3+ sensitivity (80% vs. 75%, respectively, P>0.2), while specificity improved (42% vs. 84%, respectively, P < 10-5). CONCLUSION: SOX1 and SOX14 are methylation biomarkers applicable for screening of all cervical cancer types.
Asunto(s)
Adenocarcinoma in Situ/genética , Biomarcadores de Tumor/genética , Carcinoma Adenoescamoso/genética , Carcinoma de Células Escamosas/genética , Metilación de ADN , Displasia del Cuello del Útero/genética , Neoplasias del Cuello Uterino/genética , Adenocarcinoma in Situ/patología , Adulto , Anciano , Carcinoma Adenoescamoso/patología , Carcinoma de Células Escamosas/patología , Estudios de Casos y Controles , Detección Precoz del Cáncer , Femenino , Perfilación de la Expresión Génica , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Receptores del Factor Neurotrófico Derivado de la Línea Celular Glial/genética , Proteínas de Transporte de Glicina en la Membrana Plasmática/genética , Humanos , Persona de Mediana Edad , Fenotipo , Valor Predictivo de las Pruebas , Pronóstico , Reproducibilidad de los Resultados , Factores de Transcripción SOXB1/genética , Factores de Transcripción SOXB2/genética , Proteínas de Dominio T Box/genética , Neoplasias del Cuello Uterino/patología , Frotis Vaginal , Displasia del Cuello del Útero/patologíaRESUMEN
The diagnostic performance of the widely-used Cervista HPV HR test was compared to the Hybrid Capture 2 (HC2) test in a Dutch population-based cervical cancer screening program. In 900 scrapings of women with normal cytomorphology, specificity was 90% (95%CI: 87.84-91.87) for the Cervista HPV HR test and 96% (95%CI: 94.76-97.37) for the HC2 test with 93% agreement between both tests (κâ=â0.5, p<0.001). The sensitivity for CIN2+ using 65 scrapings of women with histological-confirmed CIN2+ was 91% (95%CI: 80.97-96.51) for the Cervista HPV HR test and 92% (95%CI: 82.94-97.43) for the HC2 test with 95% agreement between both tests (κâ=â0.7, p<0.001). Fifty-seven of 60 HC2 negative/Cervista positive cases tested HPV-negative with PCR-based HPV assays; of these cases 56% were defined as Cervista triple-positive with FOZ values in all 3 mixes higher than the second cut-off of 1.93 (as set by manufacturer). By setting this cut-off at 5.0, specificity improved significantly without affecting sensitivity. External validation of this new cut-off at 5.0 in triple-positive scrapings of women selected from the SHENCCASTII database revealed that 22/24 histological normal cases now tested HPV-negative in the Cervista HPV HR test, while CIN2+ lesions remained HPV-positive. The intra-laboratory reproducibility of the Cervista HPV HR test (nâ=â510) showed a concordance of 92% and 93% for cut-off 1.93 and 5.0 (κâ=â0.83 and κâ=â0.84, p<0.001) and inter-laboratory agreement of the Cervista HPV HR test was 90% and 93% for cut-off 1.93 and 5.0 (κâ=â0.80 and κâ=â0.85, p<0.001). In conclusion, the specificity of the Cervista HPV HR test could be improved significantly by increasing the second cut-off from 1.93 to 5.0, without affecting the sensitivity of the test in a population-based screening setting.