BackgroundPap 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.MethodsA total of 27349 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.ResultsThe 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).ConclusionsThe 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.

This study evaluates the accuracy of the results of liquid-based oral brush cytology and compares it to the histology and/or the clinical follow-ups of the respective patients. A total of 1352 exfoliated specimens were collected with an Orcellex brush from an identical number of oral lesions, then cytological diagnoses were made using liquid-based cytology. The final diagnoses in the study were 105 histologically proven squamous cell carcinomas (SCCs), 744 potentially malignant lesions and 503 cases of traumatic, inflammatory or benign hyperplastic oral lesions. The sensitivity and specificity of the liquid-based brush biopsy were 95.6% (95% CI 94.5–96.7%) and 84.9% (95% CI 83.0–86.8%), respectively. This led to the conclusion that brush biopsy is potentially a highly sensitive and reliable method to make cytological diagnoses of oral neoplasia. The main advantage of a brush biopsy over a scalpel biopsy is that it is less invasive and is more tolerated by the patients. Therefore, more lesions can be screened and more cancers can be detected at an early stage.

Background: The iPath telemedicine platform Basel is mainly used for histological and cytological consultations, but also serves as a valuable learning tool. Aim: To study the level of accuracy in making diagnoses based on still images achieved by experienced cytopathologists, to identify limiting factors, and to provide a cytological image series as a learning set. Method: Images from 167 consecutive cytological specimens of different origin were uploaded on the iPath platform and evaluated by four cytopathologists. Only wet-fixed and well-stained specimens were used. The consultants made specific diagnoses and categorized each as benign, suspicious or malignant. Results: For all consultants, specificity and sensitivity regarding categorized diagnoses were 83-92 and 85-93%, respectively; the overall accuracy was 88-90%. The interobserver agreement was substantial (κ = 0.791). The lowest rate of concordance was achieved in urine and bladder washings and in the identification of benignlesions. Conclusion: Using a digital image set for diagnostic purposes implies that even under optimal conditions the accuracy rate will not exceed to 80-90%, mainly because of lacking supportive immunocytochemical or molecular tests. This limitation does not disqualify digital images for teleconsulting or as a learning aid. The series of images used for the study are open to the public at http://pathorama.wordpress.com/extragenital-cytology-2013/.

BackgroundThe rate of spontaneous regression in CIN III lesions is controversial. Whereas some studies have reported high regression rates of up to 38 % after prolonged biopsy-conus intervals, others have shown rates between 0 and 4 % without considering time intervals. Identification of young patients with potentially regressing CIN III could offer the chance to avoid conisation, thus lowering the risk of preterm labour.MethodsTo further clarify the facts, we retrospectively compared 635 biopsies showing CIN III with the diagnosis of the conisation. Either regression (CIN I or less) or non-regression (CIN II and higher) was recorded. Diagnoses were made by light microscopy and p16 immunostaining.ResultsConisation was performed between 2 and 463 days after biopsy (median 8.9 weeks). Six hundred twenty one (98 %) were HPV-HR positive. In 345 cases, HPV subtyping was available, showing HPV16 infection in 57 %. Routine processing of the conisation tissue showed no corresponding CIN lesion (< CIN II) in 40 cases (6.3 %). Additional step sectioning of the tissue revealed small CIN II+ lesions in 80 %. Finally, eight cases (1.3 %) fulfilled the criteria of regression. No regression was seen in HPV16 positive cases. Twelve invasive carcinomas were detected by routine processing of the conisation tissue.ConclusionThese results are in contrast with some prior reports that might have overestimated spontaneous regression of CIN III. Study size and an accurate discrimination between CIN II and CIN III lesions by histopathology seem to be the most likely factors to explain the diverging results published. Complete step sectioning of the whole tissue is also mandatory in questionable cases. Although theories exist that the initial biopsy might stimulate the immune system, thus triggering regression within weeks, our data do not substantially support such a mechanism. Overall, the chance of a CIN III lesion to regress rapidly within weeks or months after diagnosis seems to be small. We found more previously undetected invasive cancer than we observed regression. Therefore, a change in the current policy to treat CIN III lesions is unwarranted.

LBC facilitates the cell collection due to simpler handling and less transfer errors by dentists and may improve the overall diagnostic accuracy of oral brush biopsies in future.

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BackgroundExfoliative cytology performed on oral brush samples can help dentists to decide, whether a given oral lesion is (pre-) malignant. The use of non-invasive brush biopsies as an auxiliary tool in the diagnosis of oral mucosal lesions has gained renewed interest since improvements in cytological techniques such as the development of adjuvant diagnostic tools and liquid-based cell preparation techniques.MethodsThe aim of this study was to compare the quality of two different preparation techniques (cell collectors): the conventional transfer procedure to glass slides and the so-called liquid-based cytology preparation method. Cell smears were collected from 10 orally healthy individuals (mean age: 24 years) from the palatine mucosa at two different times (baseline and 4 weeks later). Slides of both techniques were stained by Giemsa (n = 40) and May-Gruenwald Giemsa (n = 40). The statistical analysis was performed with Excel.ResultsOn specimen analysis, the liquid-based cytology showed statistically significant improvement compared to conventional glass sides (p < 0.001). Thin layers, which were performed by liquid-based cytology showed significantly better results in the parameters (p < 0.001): uniform distribution, cellular overlapping, cellular disformation, mucus, microbial colonies and debris. The conventional glass slides approach showed more cell overlapping and contamination with extraneous material than thin layers, which were performed by Orcellex® Brush cell collectors.ConclusionsBoth techniques are diagnostically reliable. The liquid-based method showed an overall improvement on sample preservation, specimen adequacy, visualization of cell morphology and reproducibility.Liquid-based cytology simplifies cell collection due to easier handling and less transfer errors by dentists.

Objectives Oral brush biopsies are a well researched index for early detection of oral cancer in specialised centers. But the performance of the exfoliative biopsy is not yet researched in daily dental routine. Methods Private dentists and private oral surgeons in Germany took brush biopsies out of 814 suspicious lesions from 670 patients using the Orcellex brush while regular dental appointments. The analyses of the biopsies were performed by the Cytological Laboratory of Bonn (CLB) using liquid-based cytology. Results The final results were 74 oral squamous cell carcinomas and one verrucous carcinoma, histological proven, 232 cases of leukoplakia, 242 cases of lichen planus, 17 cases of erythroplakia, 259 cases of benign inflammatory, traumatic or hyperplastic oral lesions. The sensitivity for the detection of cancer cells using brush biopsy archived 100%, the specificity for the detection of non-neoplastic cells was 86.5%. The positive predictive value was 43.1%, the negative predicative value was at 100%. Conclusion The oral brush biopsy seems to be a sufficient tool for early cancer detection in private dental offices. Clinical Relevance. Generally, practicing dentists do not see various oral squamous cell carcinomas in their careers, so the experience in identifying oral squamous cell carcinomas as such is very low. The brush biopsy might help them in cases of doubt to prevent tumors from expansive growth.