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BACKGROUND: The objective of this study was to evaluate the performance of a combined approach of liquid-based anal cytology and human papillomavirus (HPV) testing in predicting patients who should undergo high-resolution anoscopy for the early detection of anal cancer and anal intraepithelial neoplasia (AIN)-2+. METHODS: We conducted a prospective single-center quality improvement study. We consecutively enrolled men who had sex with men (MSM) attending our sexually transmitted disease clinic to undergo anal Papanicolaou (Pap) and HPV tests. All patients with an abnormal anal Pap test result and/or positive HPV test result underwent high-resolution anoscopy. RESULTS: We enrolled 217 MSM, 80 HIV-positive patients, and 137 HIV-negative patients. Cytology showed a sensitivity of 100%, a specificity of 64.1%, an accuracy of 66.7%, a positive predictive value (PPV) of 15.7%, and a negative predictive value (NPV) of 100% for the detection of AIN-2+. The high-risk (HR)-HPV test showed sensitivity, specificity, accuracy, PPV, and NPV of 100%, 36.4%, 40%, 9.4%, and 100%, respectively. The combination of abnormal cytology with identification of infection by at least 1 HR-HPV strain on the HPV test had a sensitivity of 100%, a specificity of 73%, an accuracy of 74.6%, a PPV of 19.1%, and an NPV of 100%. CONCLUSION: Anal HR-HPV testing, complementary to cytology, improves the diagnostic accuracy of screening for anal cancer.
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Alphapapillomavirus , Neoplasias del Ano , Infecciones por VIH , Infecciones por Papillomavirus , Minorías Sexuales y de Género , Neoplasias del Ano/diagnóstico , Detección Precoz del Cáncer , Homosexualidad Masculina , Humanos , Masculino , Papillomaviridae , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/diagnóstico , Estudios ProspectivosRESUMEN
BACKGROUND: Cervical cancer is a major health problem in Latin America. In 2019, the Italian Agency for Development Cooperation (La Paz regional site) conducted a pilot study to estimate the prevalence of high-risk human papillomavirus (HPV) and the feasibility of HPV screening in Bolivia through self-sampling and portable and transportable laboratory instruments for HPV testing in urban and rural areas. METHODS: Women aged 20-65 years from La Paz (urban area), Toro Toro (rural area), and Acasio (rural area) were enrolled in local public health centers between Dec 1, 2019, and June 30, 2021. Self-sampling was carried out with the Viba-Brush system (Rovers, Oss, Netherlands) and samples were preserved in ThinPrep containers (Hologic Corporation, San Diego, CA, USA). The GeneXpert system (Cepheid, Sunnyvale, CA, USA) for high-risk HPV testing detects HPV E6 and E7 DNA via real-time PCR in a mobile system of easy execution requiring minimal manual intervention. The system provides results in about 1 h. The hr- HPV prevalence data, overall and partial genotyping, were analyzed considering the following age groups: 20-34, 35-44, and 45-65 years old. FINDINGS: 2168 women were enrolled: 614 (28.3%) in La Paz, 743 (34.3%) in Toro Toro, and 811 (37.4%) in Acasio. Only one sample was collected from each participant. 2043 (94.2%) of 2168 samples were adequate for HPV testing. 255 (12.5%) samples were positive for high-risk HPV. Comparing the urban area (La Paz) versus rural combined areas (Acasio+Toro Toro), using a logistic model, the HPV total rate was statistically significantly higher in the city of La Paz (15.0% vs 11.4%; OR:1.37;95% CI: 1.04-1.80). Furthermore, the HPV prevalence was declining by age, and the urban/rural odds ratio was 1.50; (95% IC 1.13-19). The overall HPV 16 positivity was 2.7% (55/2043) and for HPV 18/45 was 1.8% (37/2043) without any statistically significant differences between the three BHU enrolling centers. Only the prevalence of HPV group '39/56/66/68' was significantly higher in La Paz (p<0,001) in comparison to Acasio and Toro Toro. INTERPRETATION: The total and age-adjusted prevalence of high-risk HPV infection in rural and urban areas in Bolivia, as measured with a validated test for screening, is similar to that observed in Europe and the USA. Our study shows that a screening protocol for HPV testing with self-sampling would be feasible in urban and rural areas in Bolivia, and that the reported high occurrence of cervical cancer in Bolivia is not related to a higher rate of high-risk HPV infections. Carrying out HPV tests locally avoids the issues associated with transportation and storage of the collected material and allows the participant to wait in the clinic for the test result, overcoming the very long response time for screening test in Bolivia.
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Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , Adulto , Femenino , Humanos , Adulto Joven , Bolivia/epidemiología , Detección Precoz del Cáncer/métodos , Estudios de Factibilidad , Tamizaje Masivo , Papillomaviridae/genética , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/complicaciones , Proyectos Piloto , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/prevención & control , Persona de Mediana Edad , AncianoRESUMEN
INTRODUCTION: After the transition toward the HPV-based screening protocol, which has led to an increase in sensitivity, and in order to bring the specificity back to acceptable values, cytology underwent a change of approach, becoming a triage test. For these reasons, in the Tuscany region (after the recommendations of the GISCi document), it was decided to reduce, as much as possible, the use of ASC-US category in cytology triage, classifying these morphological cases as negative for intraepithelial lesion or malignancies (NILM) or LSIL, basing on the grade of nuclear atypia. So, in Italy, in a cytology triage context (HPV primary screening), a modified Bethesda system (TBS) is currently used. The aim of this study was to evaluate the performance of the review activity of 384 cytology triage cases and of the cervical cancer screening indicators (sensitivity and specificity for CIN2+ lesions) using the TBS 2014 or the modified TBS. MATERIALS AND METHODS: 384 HPV positive cases at one-year recall (192 with a cytology result of NILM both at baseline and at one-year recall; 192 with a cytology result of NILM at baseline but abnormal at one-year recall), all with a histologically confirmed result (128 CIN2+, 256 ≤ CIN1), were selected, and their baseline Pap tests were reviewed in blind mode by 5 expert cytologists. RESULTS: The cytological results of NILM were confirmed for 92.5% and 83.8% of cases using TBS 2014 or modified TBS, respectively. 20/128 CIN2+ cases could have been reported at the baseline cytology triage, causing an anticipatory effect and an improvement in sensitivity of the screening protocol at baseline (+15.6%). Using TBS 2014, the number of false positives more than tripled with respect to the modified TBS 2014, with a significant increase in unnecessary colposcopies (+11.4%). CONCLUSION: This work demonstrated that a greater expertise of cytologists, acquired during the following 3 years of experience with cytological triage, and a strong IQC system could lead to the identification of a significant number of lesions reported to baseline rather than at one-year recall (diagnostic anticipation).
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Infecciones por Papillomavirus , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Femenino , Humanos , Neoplasias del Cuello Uterino/patología , Displasia del Cuello del Útero/patología , Triaje , Detección Precoz del Cáncer/métodos , Reproducibilidad de los Resultados , Papillomaviridae/genéticaRESUMEN
OBJECTIVE: To evaluate performance of the first round of HPV-based screening in Tuscany region and compare it with the prior round of Pap-based screening. SETTING: Tuscany region of Italy, where HPV-based cervical cancer screening started in 2013, with a strong level of centralization screening tests at the Regional Laboratory for Cancer Prevention (ISPRO). METHODS: The transition from Pap- to HPV-based screening was initiated for older women and at 3 out of 12 Tuscany Local Health Units (LHUs). Data from the Florence and Grosseto LHUs (about 300,000 women) were analysed and performance screening indicators estimated. RESULTS: HPV-based indicators recorded good performance, with increased compliance vs. the Pap-based programme. We registered a substantial decrease in waiting times from sampling to test reporting, probably related to the centralization strategy. Since the screening protocol was the same and conducted at a single laboratory, we could hypothesize that the difference in HPV positivity (6.8% in Florence vs. 8.4% in Grosseto) was due to a real difference in HPV prevalence among women of the two LHUs. The transition to HPV-based screening led to a significant increase both in colposcopy referral rate (4.3% vs. 1.2%) and CIN2+ detection rate (8.3 vs. 3.4). CONCLUSIONS: HPV-based is more effective in detecting high-grade precancerous and cancerous lesions than Pap-based screening and is characterized by an "anticipatory effect" in the detection of CIN2+ lesions. The transition from Pap-based to HPV-based screening programme should include increased resources dedicated to colposcopy services. Centralization in a laboratory with long experience in this field promotes efficiency of the screening process.
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Infecciones por Papillomavirus , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Anciano , Colposcopía , Detección Precoz del Cáncer/métodos , Femenino , Humanos , Masculino , Tamizaje Masivo/métodos , Papillomaviridae , Infecciones por Papillomavirus/epidemiología , Embarazo , Neoplasias del Cuello Uterino/patología , Frotis Vaginal , Displasia del Cuello del Útero/diagnósticoAsunto(s)
Carcinoma/diagnóstico , Investigadores , Neoplasias del Cuello Uterino/diagnóstico , Adulto , Carcinoma/cirugía , Congresos como Asunto , Diagnóstico Diferencial , Detección Precoz del Cáncer/métodos , Femenino , Humanos , Italia , Publicaciones Periódicas como Asunto , Neoplasias del Cuello Uterino/cirugíaRESUMEN
The presence of circulating tumor cells (CTC) or microemboli (CTM) in the peripheral blood can theoretically anticipate malignancy of solid lesions in a variety of organs. We aimed to preliminarily assess this capability in patients with pulmonary lesions of suspected malignant nature. We used a cell-size filtration method (ScreenCell) and cytomorphometric criteria to detect CTC/CTM in a 3 mL sample of peripheral blood that was taken just before diagnostic percutaneous CT-guided fine needle aspiration (FNA) or core biopsy of the suspicious lung lesion. At least one CTC/CTM was found in 47 of 67 (70%) patients with final diagnoses of lung malignancy and in none of 8 patients with benign pulmonary nodules. In particular they were detected in 38 (69%) of 55 primary lung cancers and in 9 (75%) of 12 lung metastases from extra-pulmonary cancers. Sensitivity of CTC/CTM presence for malignancy was 70.1% (95%CI: 56.9-83.1%), specificity 100%, positive predictive value 100% and negative predictive value 28.6% (95%CI: 11.9-45.3%). Remarkably, the presence of CTC/CTM anticipated the diagnosis of primary lung cancer in 3 of 5 patients with non-diagnostic or inconclusive results of FNA or core biopsy, whereas CTC/CTM were not observed in 1 patient with sarcoidosis and 1 with amarthocondroma. These results suggest that presently, due to the low sensitivity, the search of CTC/CTM cannot replace CT guided percutaneous FNA or core biopsy in the diagnostic work-up of patients with suspicious malignant lung lesions. However, the high specificity may as yet indicate a role in cases with non-diagnostic or inconclusive FNA or core biopsy results that warrants to be further investigated.
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BACKGROUND: The aim of this work was to evaluate the role of human papillomavirus (HPV) testing and anal cytology, considering a population of HIV-positive and negative men who have sex with men (MSM), at high risk of sexually transmitted diseases (STD), in order to ascertain which of the methods examined is the best screening strategy for the prevention of anal cancer. METHODS: In the period 06/2013-07/2014 at the "MTS Centre" of the University of Florence, 87 male patients, homo/bi-sexual, of which 46 HIV-negative and 41 HIV-positive, were recruited for anal Pap smear and HPV testing. All patients with an "abnormal" cytological result underwent anoscopy with possible biopsy. RESULTS: HPV testing was positive in 73 patients (83.6%). Cytology was negative in 50 patients (57.5%), inconclusive in 14 patients (16.1%), abnormal in 23 patients (26.4%): 14 ASC-US (19.2%), 4 ASC-H (5.5%), 5 L-SIL (6.8%), 0 H-SIL. Anoscopy with biopsy led to diagnosis of AIN I in 10 cases, of which 6 ASC-US+ and 4L-SIL+, AIN II in only 1 case, LS-IL+. CONCLUSIONS: Anal HPV testing, when used in primary screening, lead to a high number of "false positives", given the too high prevalence of HPV infection in MSM, the highest risk population targeted for screening. So we propose a screening program with anal cytology which has a high sensitivity for detection of AIN while is a poor predictor of the severity of these lesions; therefore, all patients with abnormal anal Pap smear should undergo anoscopy with biopsy.
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Neoplasias del Ano/prevención & control , Tamizaje Masivo/métodos , Prueba de Papanicolaou/métodos , Infecciones por Papillomavirus/diagnóstico , Adolescente , Adulto , Anciano , Neoplasias del Ano/diagnóstico , Neoplasias del Ano/virología , Biopsia , Reacciones Falso Positivas , Seronegatividad para VIH , Seropositividad para VIH/epidemiología , Homosexualidad Masculina , Humanos , Italia , Masculino , Persona de Mediana Edad , Infecciones por Papillomavirus/complicaciones , Adulto JovenRESUMEN
Objective: Squamous cell carcinoma of the anus (SCCA) is associated with human papillomavirus (HPV) infection in almost 90% of the cases. Its incidence is alarmingly high among men who have sex with men (MSM) and continues to increase at an average rate of 2% per year. The objective of the present study is to evaluate the usefulness and performance of liquid-based anal cytology as a screening tool for prevention and early detection of SCCA in a cohort of at-risk men. Method: We conducted a retrospective study including 111 MSM, aged between 22 and 62 years old, who underwent anal cytological screening with a liquid-based Pap test at our sexually transmitted diseases (STDs) clinic from January 2015 to March 2017. Results: Out of 111 anal smears, 57 (51,4%) resulted negative, 42 (37,8%) abnormal, and 12 (10,8%) unsatisfactory for the cytological evaluation. Only patients with an abnormal cytology underwent anoscopy and subsequent biopsy. The histological results were as follows: negative for squamous intraepithelial lesion (SIL) in 5 cases, low-grade SIL (L-SIL) in 21, high-grade SIL (H-SIL) in 5, SCCA in 1. Five patients had a normal anoscopy and biopsy was not taken. Conclusion: Liquid-based cytology, reducing the "darkening factors" typical for the conventional smears, has a higher positive predictive value than the traditional technique. Moreover, a cytological diagnosis of atypical squamous cells of undetermined significance (ASC-US) or L-SILmay hide a severe dysplasia or even a carcinoma. Thus, all patients with an abnormal anal cytology at any grade should be considered for anoscopy. (AU)
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Humanos , Masculino , Adulto , Persona de Mediana Edad , Neoplasias del Ano/prevención & control , Citodiagnóstico/métodos , Minorías Sexuales y de Género , VIH , Infecciones por Papillomavirus/diagnósticoRESUMEN
PURPOSE: Timing and magnitude of blood release of circulating tumour cells (CTC) and circulating tumour microemboli (CTM) from primary solid cancers are uncertain. We investigated prevalence and number of CTC and CTM at diagnosis of advanced non-small cell lung cancer (NSCLC). METHODS: Twenty-eight consecutive patients with suspected stage III-IV lung cancer gave consent to provide 15 mL of peripheral blood soon before diagnostic CT-guided fine-needle aspiration biopsy (FNAB). CTC and CTM (clusters of ≥3 CTC) were isolated by cell size filtration (ScreenCell), identified and counted by cytopathologists using morphometric criteria and (in 6 cases) immunostained for vimentin. RESULTS: FNAB demonstrated NSCLC in 26 cases. At least one CTC/3 mL blood (mean 6.8 ± 3.7) was detected in 17 (65 %) and one CTM (mean 4.5 ± 3.3) in 15 (58 %) of 26 NSCLC cases. No correlation between number of CTC or CTM and tumour type or stage was observed. Neoplastic cells from both FNA and CTC/CTM were positive for vimentin but heterogeneously. CONCLUSIONS: CTC can be detected in two-thirds and CTM in more than half of patients with advanced NSCLC at diagnosis. Reasons underlying lack of CTC and CTM in some advanced lung cancers deserve further investigations.
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Adenocarcinoma/secundario , Biomarcadores de Tumor/sangre , Carcinoma de Pulmón de Células no Pequeñas/secundario , Carcinoma de Células Escamosas/secundario , Neoplasias Pulmonares/patología , Células Neoplásicas Circulantes/patología , Adenocarcinoma/metabolismo , Anciano , Anciano de 80 o más Años , Biopsia con Aguja Fina , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Células Escamosas/metabolismo , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/metabolismo , Metástasis Linfática , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Vimentina/metabolismoRESUMEN
PURPOSE: The aim of this study was to assess the usefulness of having a cytopathologist present during percutaneous CT-guided fine needle aspiration (FNA) of pulmonary lesions. MATERIALS AND METHODS: Three hundred and twenty-one FNAs of lung lesions were performed in 312 patients (218 males, 94 females; age range: 20-86 years; mean age: 66 yrs). Nodule sizes ranged from 0.5 to 8 cm. The sampling was performed by a radiologist under CT-guidance; the calibre of the needle used was 20-25 G. Smears were prepared in the Radiology Department and stained using a quick method by a cytopathologist: the sample adequacy was assessed and, if possible, a preliminary diagnosis was made. An additional FNA was requested if the first aspirate was considered diagnostically inadequate. The diagnostic accuracy was examined by reviewing the clinical data and by correlating with the histological material and the clinical outcome. RESULTS: Satisfactory diagnostic material was obtained in 275 of the 321 FNA (86%): 231 were malignant (72%), 8 suspicious (3%) and 36 were negative for malignancy (11%). Forty-six of the 321 specimens (14%) were considered inadequate for any diagnostic verification. An additional FNA was performed immediately in 60 cases (19%). Forty-two subjects developed pneumothorax: 21 patients (50%) of these required thoracic drainage. Blood effusion around the lesion site or adjacent to the needle path was observed in 39 patients (12%). Sensitivity was 99%, specificity was 95% and diagnostic accuracy was 99%. CONCLUSIONS: CT guided aspiration cytology can be a safe and fast procedure for lung nodule characterisation. On-site immediate evaluation of FNA specimens can be beneficial in determining the adequacy of the aspirate and in providing accurate preliminary diagnoses of the specimens, thus allowing for rapid clinical decisions.
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Adenocarcinoma/patología , Biopsia con Aguja/métodos , Carcinoma Adenoescamoso/patología , Carcinoma de Células Escamosas/patología , Neoplasias Pulmonares/patología , Pulmón/patología , Tomografía Computarizada por Rayos X , Adenocarcinoma/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Adenoescamoso/diagnóstico , Carcinoma de Células Escamosas/diagnóstico , Citodiagnóstico , Diagnóstico Diferencial , Femenino , Humanos , Neoplasias Pulmonares/diagnóstico , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Neumotórax/diagnóstico por imagen , Radiografía TorácicaRESUMEN
BACKGROUND: The identification of specific morphologic diagnostic criteria is of paramount importance to optimize the accuracy of fine-needle aspiration cytology (FNAC) and to reduce the rate of false-negative results. In the current study, the authors reviewed a consecutive series of false-negative findings observed in the study center to define the presence and degree of cytologic abnormalities. False-negative cases were randomly mixed with true-negative cases and were reviewed by a panel of expert readers in a blinded fashion. The main objective of the current study was to identify a morphologic pattern that may permit the reduction of false-negative findings while maintaining the specificity of FNAC. METHODS: A blind review of a set of 41 consecutive false-negative and 49 true-negative breast aspiration samples was performed by a panel of 10 expert cytologists who were asked to give a final report and to classify the samples according to classic morphologic parameters. RESULTS: The majority final report sensitivity was 54% (range, 19-61%) and specificity was 73% (range, 65-92%). The average concordance with the majority report, adjusted for chance agreement (kappa statistic), was moderate at 0.54 (range, 0.40-0.65). Enlarged nuclear size, a hyperchromatic nucleus, the absence of naked nuclei, and the absence of apocrine metaplasia were reported more frequently in carcinoma cases, although not to a significant extent. The only variable found to be associated significantly (P = 0.041) with a diagnosis of carcinoma was the presence of microcalcifications, which nevertheless were found to occur in only a minority of carcinoma cases (7 of 41 cases) or controls (2 of 49 controls). Multivariate analysis demonstrated that the presence of microcalcifications (odds ration [OR] of 3.0; 95% confidence interval [95% CI], 1.2-7.4), the absence of naked nuclei (OR of 2.4; 95% CI, 1.3-4.4), and enlargement of the nucleus (OR of 1.9; 95% CI, 1.1-3.4) were all independently associated with false-negative findings. Diagnostic accuracy using a morphology-based score did not appear to improve the results substantially compared with the final report (sensitivity of 0.46 vs. 0.54 [P = 0.508] and a specificity of 0.80 vs. 0.73 [P = 0.218]). CONCLUSIONS: The results of the current study confirm that breast FNAC false-negative results are at least partially the result of underreporting of abnormalities that may be noted at review. Detailed analysis of a single morphologic characteristic was found to be of limited diagnostic value, suggesting that operators do perceive abnormalities but cannot translate these findings into distinct morphologic categories.
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Biopsia con Aguja Fina , Neoplasias de la Mama/patología , Enfermedades de la Mama/patología , Estudios de Cohortes , Intervalos de Confianza , Citodiagnóstico/normas , Citodiagnóstico/tendencias , Diagnóstico Diferencial , Reacciones Falso Negativas , Femenino , Humanos , Inmunohistoquímica , Análisis Multivariante , Estadificación de Neoplasias , Variaciones Dependientes del Observador , Oportunidad Relativa , Curva ROC , Medición de Riesgo , Sensibilidad y Especificidad , Manejo de EspecímenesRESUMEN
BACKGROUND: The AutoPap 300 QC system (Tripath Imaging, Inc., Burlington, NC) is an automated device that was designed to screen conventionally prepared cervical smears and, more recently, thin-layer slide preparations. The system has been tested in large clinical trials. METHODS: A total of 14,145 cervical smears obtained from participants in the Florence screening program were eligible for the study. Smears were processed first with the AutoPap system and were classified into three different categories: 1) no further review (NFR), 2) review, and 3) process review (PR). Conventional manual reading was performed by 10 experienced cytopathologists. RESULTS: After AutoPap processing, 2398 smears were classified as NFR (16.9%), and 1818 smears were classified as PR (12.8%). Overall, there were 188 inadequate smears (1.3%) at conventional review and 125 inadequate smears (0.88%) at AutoPap review. Six-month repeat smears were prompted by 330 conventional reviews (2.3%) and by 222 AutoPap reviews (1.56%). Similarly, referral to colposcopy was prompted by 179 conventional reviews (1.2%) and by 147 AutoPap reviews (1.0%). Overall, 32 patients were diagnosed with high-grade cervical intraepithelial neoplasia as a result of assessment. Conventional reading detected 31 patients (28 patients were referred for colposcopy, and 3 patients were referred for repeat cytology), and the AutoPap system detected 30 patients (27 patients were referred for colposcopy, and 3 patients were referred for repeat cytology). CONCLUSIONS: The current experience suggested that conventional reading and AutoPap reading of cervical smears had essentially the same sensitivity, with slightly greater specificity for the AutoPap system. Thus, comparisons of the AutoPap system and conventional reading should focus mainly on cost analysis.