J.L. Benedet

Accuracy of Colposcopy in the Diagnostic Setting Compared With the Screening Setting

OBJECTIVE: To estimate the accuracy of colposcopy to identify cervical precancer in screening and diagnostic settings. METHODS: As part of a larger clinical trial to evaluate the diagnostic accuracy of optical spectroscopy, we recruited 1,850 patients into a diagnostic or a screening group depending on their history of abnormal findings on Papanicolaou tests. Colposcopic examinations were performed and biopsies specimens obtained from abnormal and normal colposcopic sites for all patients. The criterion standard of test accuracy was the histologic report of biopsies. We calculated sensitivities, specificities, likelihood ratios, receiver operating characteristic curves, and areas under the receiver operating characteristic curves. RESULTS: The prevalence of high-grade squamous intraepithelial lesions (HSIL) or cancer was 29.0% for the diagnostic group and 2.2% for the screening group. Using a disease threshold of HSIL, colposcopy had a sensitivity of 0.983 and a specificity of 0.451 in the diagnostic group when the test threshold was low-grade squamous intraepithelial lesions (LSIL), and a sensitivity of 0.714 and a specificity of 0.813 when the test threshold was HSIL. Using the same HSIL disease threshold, in the screening group, colposcopy had a sensitivity of 0.286 and a specificity of 0.877 when the test threshold was LSIL, and a sensitivity of 0.191 and a specificity of 0.961 when the threshold was HSIL. The colposcopy area under the receiver operating characteristic curve was 0.821 (95% confidence interval 0.79–0.85) in the diagnostic setting compared with 0.587 (95% confidence interval 0.56–0.62) in the screening setting. Changing the disease threshold to LSIL demonstrated similar patterns in the tradeoff of sensitivity and specificity and measure of accuracy. CONCLUSION: Colposcopy performs well in the diagnostic setting and poorly in the screening setting. Colposcopy should not be used to screen for cervical intraepithelial neoplasia. LEVEL OF EVIDENCE: II

The Performance of Human Papillomavirus High-Risk DNA Testing in the Screening and Diagnostic Settings

Objective: We sought to evaluate the performance of the human papillomavirus high-risk DNA test in patients 30 years and older. Materials and Methods: Screening (n = 835) and diagnosis (n = 518) groups were defined based on prior Papanicolaou smear results as part of a clinical trial for cervical cancer detection. We compared the Hybrid Capture II (HCII) test result with the worst histologic report. We used cervical intraepithelial neoplasia (CIN) 2/3 or worse as the reference of disease. We calculated sensitivities, specificities, positive and negative likelihood ratios (LR+ and LR−), receiver operating characteristic (ROC) curves, and areas under the ROC curves for the HCII test. We also considered alternative strategies, including Papanicolaou smear, a combination of Papanicolaou smear and the HCII test, a sequence of Papanicolaou smear followed by the HCII test, and a sequence of the HCII test followed by Papanicolaou smear. Results: For the screening group, the sensitivity was 0.69 and the specificity was 0.93; the area under the ROC curve was 0.81. The LR+ and LR− were 10.24 and 0.34, respectively. For the diagnosis group, the sensitivity was 0.88 and the specificity was 0.78; the area under the ROC curve was 0.83. The LR+ and LR− were 4.06 and 0.14, respectively. Sequential testing showed little or no improvement over the combination testing. Conclusions: The HCII test in the screening group had a greater LR+ for the detection of CIN 2/3 or worse. HCII testing may be an additional screening tool for cervical cancer in women 30 years and older. (Cancer Epidemiol Biomarkers Prev 2008;17(10):2865–71)

The accuracy of the papanicolaou smear in the screening and diagnostic settings

Objective. We evaluated the performance of the Papanicolaou smear in screening and diagnostic settings. Study Design. We analyzed Papanicolaou smear results of 1,850 women recruited into a clinical trial to evaluate an emerging technology for the detection of cervical cancer. Screening and diagnosis groups were based on the history of previous Papanicolaou smear results. We calculated sensitivities, specificities, positive and negative likelihood ratios (LR+ and LR−), receiver operating characteristic curves, and areas under the receiver operating characteristic curve (AUC). Results. In the screening group, by defining disease as cervical intraepithelial neoplasia (CIN) 2,3/cancer or worse and using high-grade squamous intraepithelial lesion (HSIL) as the test cutpoint, the AUC was 0.689, and the LR+ and LR− were 39.25 and 0.67, respectively. In the diagnosis group, the AUC was 0.764, and the LR+ and LR− were 3.79 and 0.56, respectively. By defining disease as human papillomavirus/CIN 1 or worse and HSIL as the test cutpoint, the AUC was 0.586, and the LR+ and LR− were 17.01 and 0.92 in the screening group; in the diagnosis group, the AUC was 0.686, and the LR+ and LR− were 2.77 and 0.75, respectively. Conclusions. In a screening setting, a Papanicolaou smear result of HSIL or worse is 39 times more likely in a patient with CIN 2,3/cancer than in a patient without it. This compares to 4 times more likely in the diagnostic setting. The magnitude of the positive likelihood ratio observed in the screening group indicated that abnormal Papanicolaou smear results obtained in the screening setting should have more impact on clinical decision making than those from results obtained in the diagnostic setting.

Exactitud de la citología de Papanicolaou en contextos de cribaje y de diagnóstico

Objetivo. Hemos evaluado el rendimiento de la citología de Papanicolaou en contextos de cribaje y de diagnóstico. Diseño del estudio. Analizamos los resultados de las citologías de 1.850 mujeres reclutadas para un ensayo clínico en el que se evaluó una nueva tecnología para la detección del cáncer cervical. Los grupos de cribaje y de diagnóstico se definieron en función de los antecedentes de resultados de citología previos. Calculamos las sensibilidades, especificidades, proporciones de probabilidades positivas y negativas (LR+ y LR‐), curvas de características operativas del receptor y áreas bajo las curvas de características operativas del receptor (AUC). Resultados. En el grupo de cribaje, si se definía la enfermedad como una neoplasia intraepitelial cervical (CIN) 2,3/cáncer o superior, y se utilizaba como valor de corte de la prueba la lesión intraepitelial escamosa de alto grado (HSIL), el AUC era de 0,689, y la LR+ y LR‐ eran de 39,25 y 0,67, respectivamente. En el grupo de diagnóstico, el AUC fue de 0,764, y la LR+ y la LR‐ fueron de 3,79 y 0,56, respectivamente. Si se definía la enfermedad como virus del papiloma humano/CIN 1 o superior y se utilizaba como punto de corte la HSIL, el AUC era de 0,586, y la LR+ y LR‐ eran de 17,01 y 0,92 en el grupo de cribaje; mientras que en el grupo de diagnóstico, el AUC era de 0,686, y la LR+ y la LR‐ eran de 2,77 y de 0,75, respectivamente. Conclusiones. En un contexto de cribaje, un resultado del frotis de Papanicolaou de HSIL o superior es 39 veces más probable en una paciente con CIN 2,3/cáncer que en una paciente que no lo presenta. En un contexto diagnóstico esta probabilidad es 4 veces superior. La magnitud de la proporción de probabilidad positiva observada en el grupo de cribaje indicaba que los resultados anormales de la citología obtenidos en ese contexto debieran tener una repercusión en la toma de decisiones clínicas superior a la de los resultados obtenidos en el contexto diagnóstico. ▪