Epidermal growth factor receptor gene numerical aberrations are frequent events in actinic keratoses and invasive cutaneous squamous cell carcinomas.

Epidermal growth factor receptor (EGFR) gene amplification and protein overexpression are common in several cancers. EGFR status has seldom been studied in cutaneous squamous carcinomas (SCCs), or their precursors, actinic keratoses (AKs). We evaluated the presence of EGFR genomic aberrations and EGFR protein overexpression in 25 AKs and 35 invasive SCCs by means of fluorescence in situ hybridization (FISH) and immunohistochemistry. EGFR numerical aberrations were detected in 52% of AKs and 77.1% of SCCs (P = 0.042). EGFR amplification was identified in 12% of AKs and 20% of SCCs. No differences regarding EGFR numerical aberrations were observed when AKs with high-grade dysplasia were compared with SCCs. A good correlation was observed between EGFR numerical aberrations and EGFR overexpression. Our results suggest that EGFR numerical aberrations occur in the early stages of epithelial carcinogenesis in skin, not playing a role in the progression from low-grade SCCs into more aggressive phenotypes.

Prospective evaluation of p16/Ki-67 dual-stained cytology for managing women with abnormal Papanicolaou cytology: PALMS study results.

BACKGROUND: Testing for the presence of the human papillomavirus (HPV) is widely accepted for triaging Papanicolaou cytology results categorized as atypical squamous cells of undetermined significance (ASC-US). In contrast, HPV testing has limited use in triaging cytological low-grade squamous intraepithelial lesions (LSILs) due to prevalence rates of typically >80%. In the current study, the authors assessed the diagnostic performance of p16/Ki-67 dual-stained cytology in triaging ASC-US and LSIL cases within the prospective, multicentric Primary ASC-US LSIL Marker Study (PALMS). METHODS: A total of 575 ASC-US cases and 529 LSIL cases from a cohort of 27,349 women who were prospectively enrolled into the PALMS study in 5 European countries were tested with p16/Ki-67 dual-stained cytology and Hybrid Capture 2 (HC2) HPV testing. Colposcopy-guided biopsy results of cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) were used as clinical endpoints. RESULTS: p16/Ki-67 dual-stained cytology demonstrated comparable (ASC-US: 94.4% for dual-stained cytology vs 100% for HC2 testing; P = .317) or lower (LSIL: 85.7% for dual-stained cytology vs 98.4% for HC2 testing; P = .005) sensitivity for CIN2+, but higher levels of specificity compared with HC2 HPV testing in both ASC-US (78.7% vs 60.4%; P<.001) and LSIL (53.3% vs 15.6%; P<.001) cases. Positive predictive values for CIN2+ were substantially higher for dual-stained cytology versus HC2 HPV testing, especially in LSIL, and in ASC-US cases for women aged <30 years. CONCLUSIONS: The clinical usefulness and efficiency of triaging women with ASC-US or LSIL Papanicolaou cytology results by p16/Ki-67 dual-stained cytology testing has been confirmed in this prospective, pan-European study. The high positive predictive value of dual-stained cytology for the presence of high-grade CIN may help to reduce the number of unnecessary colposcopy referrals.

Screening for cervical cancer precursors with p16/Ki-67 dual-stained cytology: results of the PALMS study.

BACKGROUND: Pap cytology is known to be more specific but less sensitive than testing for human papillomavirus (HPV) for the detection of high-grade cervical intraepithelial neoplasia (CIN2+). We assessed whether p16/Ki-67 dual-stained cytology, a biomarker combination indicative of transforming HPV infections, can provide high sensitivity for CIN2+ in screening while maintaining high specificity. Results were compared with Pap cytology and HPV testing. METHODS: A total of 27,349 women 18 years or older attending routine cervical cancer screening were prospectively enrolled in five European countries. Pap cytology, p16/Ki-67 immunostaining, and HPV testing were performed on all women. Positive test results triggered colposcopy referral, except for women younger than 30 years with only positive HPV test results. Presence of CIN2+ on adjudicated histology was used as the reference standard. Two-sided bias-corrected McNemar P values were determined. RESULTS: The p16/Ki-67 dual-stained cytology positivity rates were comparable with the prevalence of abnormal Pap cytology results and less than 50% of the positivity rates observed for HPV testing. In women of all ages, dual-stained cytology was more sensitive than Pap cytology (86.7% vs 68.5%; P < .001) for detecting CIN2+, with comparable specificity (95.2% vs 95.4%; P = .15). The relative performance of the tests was similar in both groups of women: younger than age 30 and 30 years or older. HPV testing in women 30 years or older was more sensitive than dual-stained cytology (93.3% vs 84.7%; P = .03) but less specific (93.0% vs 96.2%; P < .001). CONCLUSIONS: The p16/Ki-67 dual-stained cytology combines superior sensitivity and noninferior specificity over Pap cytology for detecting CIN2+. It suggests a potential role of dual-stained cytology in screening, especially in younger women where HPV testing has its limitations.

[Anal intraepithelial neoplasia: application of a diagnostic protocol in risk patients using anal cytology]. / Neoplasia intraepitelial anal: resultados de la aplicación de un protocolo diagnóstico en pacientes de riesgo mediante el uso de citología anal.

INTRODUCTION: Anal intraepithelial neoplasia is a precursor condition of squamous anal carcinoma. The groups at risk of this lesion are patients with anogenital condylomata, cervical dysplasia, human immunodeficiency virus infection and, in general, patients with HPV infection. The aim of this study was to analyse the results of a diagnostics protocol of Anal Intraepithelial Neoplasia in high risk population using anal cytology. PATIENTS AND METHOD: The protocol is based on a visit in the outpatient department, clinical interview, physical examination and anal cytology evaluated by Bethesda criteria. The cross-sectional observational study was designed to study the anal smear results and their relationship with risk factors. RESULTS: A total of 64 patients were included from January 2005 to December 2006. In the overall series, 25 patients have been diagnosed with abnormal anal cytology: 9 atypical squamous cells of undetermined significance (ASCUS), 15 low-grade and 1 high-grade squamous intraepithelial lesions. There were no significant associations between abnormal cytology results and the presence of anal condyloma (p = 0.22). Neither were there statistical associations found with high risk-HPV infection (p = 0.84), HIV infection (p = 0.98) or tobacco use (p = 0.14). CONCLUSIONS: Our diagnostic protocol of anal intraepithelial neoplasia revealed 25% of patients with pre-invasive lesions of squamous anal cancer.

Neoplasia intraepitelial anal: resultados de la aplicación de un protocolo diagnóstico en pacientes de riesgo mediante el uso de citología anal / Anal intraepithelial neoplasia: application of a diagnostic protocol in risk patients using anal cytology

Introducción. La neoplasia intraepitelial anal es una lesión precursora del carcinoma escamoso anal. Se considera población en riesgo de padecer esta lesión a los pacientes con condilomas anogenitales, historia previa de displasia de cérvix, infección por VIH y en general los pacientes con infección por el VPH. El objetivo de este estudio es analizar los resultados de la aplicación de un protocolo diagnóstico de neoplasia intraepitelial anal en población de riesgo mediante el empleo de citología anal. Material y método El protocolo diagnóstico de neoplasia intraepitelial anal consistió en realizar una anamnesis estructurada, exploración física y citología anal, la cual se interpretó mediante los criterios de Bethesda. En este estudio observacional de corte transversal se analizan los resultados de diagnóstico de neoplasia intraepitelial anal y su asociación con factores de riesgo. Resultados Se incluyó a 64 pacientes en los que se diagnosticaron 25 alteraciones citológicas: 9 alteraciones citológicas de significado incierto o ASCUS, 15 casos de neoplasia intraepitelial anal de bajo grado y 1 de alto grado. Al relacionar la presencia de alteraciones en la citología anal con los factores de riesgo conocidos, no hubo asociación estadísticamente significativa con la presencia de condilomas (p=0,22), infección por VPH de alto riesgo (p=0,84), infección por VIH (p=0,98) o tabaquismo (p=0,14).Conclusiones La aplicación de un protocolo de detección de neoplasia intraepitelial anal en población de riesgo ha permitido detectar un 25% de pacientes con lesiones precursoras de carcinoma anal (AU)

Introduction. Anal intraepithelial neoplasia is a precursor condition of squamous anal carcinoma. The groups at risk of this lesion are patients with anogenital condylomata, cervical dysplasia, human immunodeficiency virus infection and, in general, patients with HPV infection. The aim of this study was to analyse the results of a diagnostics protocol of Anal Intraepithelial Neoplasia in high risk population using anal cytology. Patients and method The protocol is based on a visit in the outpatient department, clinical interview, physical examination and anal cytology evaluated by Bethesda criteria. The cross-sectional observational study was designed to study the anal smear results and their relationship with risk factors .Results A total of 64 patients were included from January 2005 to December 2006. In the overall series, 25 patients have been diagnosed with abnormal anal cytology: 9 atypical squamous cells of undetermined significance (ASCUS), 15 low-grade and 1 high-grade squamous intraepithelial lesions. There were no significant associations between abnormal cytology results and the presence of anal condyloma (p=0.22). Neither were there statistical associations found with high risk-HPV infection (p=0.84), HIV infection (p=0.98) or tobacco use (p=0.14).Conclusions Our diagnostic protocol of anal intraepithelial neoplasia revealed 25% of patients with pre-invasive lesions of squamous anal cancer (AU)

Citología en medio líquido (Thin Prep Pap Test). Un año de experiencia / Liquid-based cytology (Thin Prep Pap Test). A one-year experience

Objetivos: Evaluar nuestra experiencia en citología en medio líquido (Thin Prep Pap Test) durante un año, evaluando el seguimiento de las pacientes diagnosticadas. Comparar estos datos con nuestros resultados obtenidos previamente con citología convencional. Sujetos y métodos: Se realizaron 11.150 citologías cervicovaginales, 8.086 convencionales y 3.064 en medio líquido (Thin Prep Pap Test) y se evaluaron los resultados. Se efectuó un seguimiento de las pacientes y una evaluación de éste en los casos diagnosticados como células escamosas atípicas de significado incierto y como lesión escamosa intraepitelial de bajo grado. Resultados: Los resultados obtenidos demuestran un incremento de los diagnósticos en todas las categorías, si bien sólo de forma estadísticamente significativa si evaluamos los resultados en conjunto, no por separado. En cuanto al seguimiento, los resultados son similares en la citología convencional y en el Thin Prep. Conclusiones: La citología en medio líquido incrementa de forma más o menos significativa la detección de las lesiones cervicales preneoplásicas y, por tanto, mejora el rendimiento de la citología cervicovaginal

Objectives: To describe our experience of liquid-based cytology (Thin Prep Pap Test) over a 1-year period by evaluating the follow-up of patients with an abnormal result and to compare the results obtained with the Thin Prep Pap Test with those previously obtained with conventional cytology. Subjects and methods: The results of 11,150 cervico-vaginal pap tests (8,086 conventional tests and 3,064 liquid-based tests [Thin Prep]) were evaluated. The follow-up of patients with a diagnosis of atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LSIL) was evaluated. Results: Diagnosis of abnormal results in all categories increased, although this increase was only statistically significant when the results were evaluated as a whole. The results of follow-up were similar with both methods. Conclusions: Liquid-based cytology (Thin Prep Pap Test) substantially increases the detection of preneoplastic cervical lesions and consequently improves the yield of cervico-vaginal cytology