Cervical cancer screening has enabled a decrease in the incidence and mortality of cervical cancer. Various screening modalities have been studied to date. In many countries, screening is still based ...on cervical cytology, where cervical cells obtained either on glass or in a liquid medium are examined under a microscope. However, the fact that the vast majority of cervical cancers are a result of persistent infection with high-risk human papillomaviruses (hr-HPV) has led to the implementation of primary HPV screening in many countries. Taking into consideration the fact that the majority of HPV infections are transient and do not cause cervical precancer, effective triage methods are needed to prevent an increase in colposcopy referrals. Among these, the most extensively investigated are HPV genotyping, HPV methylation, and p16/Ki67 dual staining. In this manuscript, we briefly summarize the current knowledge regarding different screening strategies for the prevention of cervical cancer, with a focus on p16/Ki67 dual staining. In addition, we provide an explanation regarding the rationale for the use of various screening modalities based on the molecular biology of cervical cancer and cervical precancerous lesions.
Very limited information exists about the role of p16/Ki67 dual staining on glandular cells in detecting glandular precancerous lesions and cervical adenocarcinoma. In this study, we investigated the ...diagnostic accuracy of p16/Ki67 dual staining for the detection of glandular and squamous lesions on the uterine cervix and for cancer of the upper reproductive tract. We performed a retrospective analysis of prospectively collected data on 96 patients with glandular cell abnormalities. We analyzed the diagnostic accuracy of p16/Ki67 dual staining for atypical glandular cells, not otherwise specified (AGC-NOS); atypical glandular cells, favor neoplastic (AGC-FN); adenocarcinoma in situ (AIS); and A-CA (cervical adenocarcinoma). A separate analysis for the detection of squamous precancerous lesions and squamous-cell carcinoma (CIN3+) and for cancer of the upper reproductive tract (EC/OC) was performed. Among patients who had normal histology or a low-grade lesion on final analysis, only 8.5% had positive dual staining. On the other hand, 85.7% of patients with AIS+ on final histology had positive dual staining. The respective specificities of p16/Ki67 dual staining on AGC-NOS for the detection of AIS+ (adenocarcinoma in situ or cervical adenocarcinoma), CIN3+ and EC/OC were 91.5%, 88.7% and 86.4%. High specificity values of p16/Ki67 dual staining on cervical smears labelled as AGC-NOS for the detection of CIN3+ and AIS+ suggest that this method might be a useful addition in cervical cancer screening.
The interpretation of postmenopausal smears and the gynecological treatment of these patients can often be difficult. The objective of this study was to assess the performance of p16/Ki-67 ...dual-stained cytology as a triage of atypical squamous cells of undetermined significance and low-grade intraepithelial lesion cytology results in postmenopausal women.
All consecutive atypical squamous cells of undetermined significance and low-grade intraepithelial lesion smears in 1-year period were collected and p16/Ki-67 immunostaining was performed retrospectively. The results were compared with histology results or long-term cytology follow-up in cases with no biopsy.
The sensitivity of p16/Ki-67 immunostaining for the detection of cervical intraepithelial neoplasia (CIN) 2 and CIN 3 was 57.1% and 85.0%, respectively. The specificity for the detection of CIN 2 was 94.3% and CIN 3 92.4%. Negative predictive values for the detection of CIN 2 and CIN 3 were 96.3% and 99.6%, respectively.
Dual p16/Ki-67 immunostaining is a useful additional method in postmenopausal patients with low-grade cytology. Considering the high specificity and negative predictive value in our study, we believe that it could be helpful in avoiding unnecessary referrals to colposcopy and thus reduce the cost of the program.
(1) Background: There are limited data on the success of conservative treatment of high-grade cervical squamous intraepithelial lesions (HSIL) with imiquimod directly compared to standard of ...treatment with LLETZ. (2) Methods: Patients aged 18-40 with histological HSIL (with high-grade cervical intraepithelial neoplasia, CIN2p16+ and CIN3), were randomly assigned to treatment with imiquimod or LLETZ. The primary outcome was defined as the absence of HSIL after either treatment modality. The secondary outcomes were the occurrence of side effects. (3) Results: 52 patients were allocated in each group and were similar regarding baseline characteristics. In the imiquimod group, 82.7% of patients completed treatment, which was successful in 51.9%. All patients in the LLETZ group completed treatment, which was successful in 92.3% (
< 0.001). In the subgroup of CIN2p16+ patients, treatment with imiquimod was not inferior to LLETZ (73.9% vs. 84.2%,
= 0.477). During and after treatment, no cases of progression to cancer were observed. Side effects and severe side effects (local and systemic) were more prevalent in the imiquimod than in the LLETZ group (88.5% vs. 44.2% (
-value < 0.001) and 51.9% vs. 13.5% (
-value < 0.001), respectively). (4) Conclusion: Generally, in patients with HSIL, LLETZ remains the gold standard of treatment. However, in a subgroup analysis of patients with CIN2p16+, the success rate was comparable between the two treatment modalities. Due to the prevalence of side effects, the treatment compliance with imiquimod use may, however, present a clinically important issue.
p16/Ki-67 dual immunocytochemical staining (DS) has been proven as a sensitive and specific test for triage of HPV positive women with good reproducibility and accuracy. However, implementation of ...the test into an organized screening program (OSP) is not easy. The aims of this study were to compare the performance and agreement of DS results among three Slovenian cytopathological laboratories involved in the national OSP, and to define cases where staining results can be difficult to interpret.
Cervical smears were obtained for DS from 129 women referred to colposcopy. Smears were evaluated blindly in three laboratories by a cytotechnologist and a cytopathologist after initial training. Results were positive, suspicious, negative or inadequate. Five characteristics of DS staining were recorded. After primary evaluation, an extensive expert-led additional training was undertaken, including a discussion of difficult cases and a practical exam. Smears were re-evaluated and results compared to primary evaluation.
After the additional training, the overall percentage of agreement among the three laboratories increased from 77.5 to 89.9% and kappa increased from 0.70 to 0.86. Sensitivity for CIN2+ increased in two laboratories, to 90.5 and 85.7%, without the loss of specificity (75.8%). In one laboratory, the sensitivity slightly decreased from 90.5 to 88.9%, but the specificity increased from 63.6 to 68.2%. Difficult cases had significantly less DS cells, weak intensity of p16 staining, suboptimal cell morphology and background staining compared to positive cases.
Additional expert-led training and discussion of difficult cases are necessary for accurate interpretation of DS in laboratories involved in OSP. The most difficult cases were those with single stained cells and weak p16 staining. Training protocol for safe implementation of p16/Ki-67 DS in OSP is proposed.
The aim of the study was to evaluate if artificial neural networks can predict high-grade histopathology results after conisation from risk factors and their combinations in patients undergoing ...conisation because of pathological changes on uterine cervix.
We analysed 1475 patients who had conisation surgery at the University Clinic for Gynaecology and Obstetrics of University Clinical Centre Maribor from 1993-2005. The database in different datasets was arranged to deal with unbalance data and enhance classification performance. Weka open-source software was used for analysis with artificial neural networks. Last Papanicolaou smear (PAP) and risk factors for development of cervical dysplasia and carcinoma were used as input and high-grade dysplasia Yes/No as output result. 10-fold cross validation was used for defining training and holdout set for analysis.
Bas eline classification and multiple runs of artificial neural network on various risk factors settings were performed. We achieved 84.19% correct classifications, area under the curve 0.87, kappa 0.64, F-measure 0.884 and Matthews correlation coefficient (MCC) 0.640 in model, where baseline prediction was 69.79%.
With artificial neural networks we were able to identify more patients who developed high-grade squamous intraepithelial lesion on final histopathology result of conisation as with baseline prediction. But, characteristics of 1475 patients who had conisation in years 1993-2005 at the University Clinical Centre Maribor did not allow reliable prediction with artificial neural networks for every-day clinical practice.
The management of women with Pap cytology results categorized as "atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion" (ASC-H) can often be challenging. We assessed the ...performance of p16/Ki67 dual-stained cytology as a potential triage tool for the detection of biopsy-confirmed high-grade squamous intraepithelial lesions (HSILs) in women with ASC-H.
Women with ASC-H were followed for a period of 36 months by repeat cytology and colposcopy. p16/Ki67 dual staining was performed retrospectively on the initial Pap cytology slide with ASC-H interpretation. Results were compared with the final histological diagnosis and/or cytological follow-up for at least 1 year. All outcomes were defined as clinically significant at the threshold of HSIL (cervical intraepithelial neoplasia grade 2 or worse).
One hundred sixty-nine cases fulfilled all conditions to be included in the study group. The rate of histologically confirmed HSIL was 57.4%, low-grade squamous intraepithelial lesion was diagnosed in 17.7% of the patients and normal histology or follow-up in 24.9% of the patients. Overall sensitivity and specificity of p16/Ki67 dual stain were 95% and 72%, respectively. Overall positive likelihood ratio of p16/Ki67 in detection of HSIL was 3.41, considerably increasing pretest probability from 57% to posttest probability of 82%.
A substantial subset of patients with ASC-H interpretations is associated with an appreciable risk of clinically significant cervical disease. p16/Ki67 dual stain can provide additional valuable information that may lead to higher-quality management of women with ASC-H, especially when initial colposcopy or biopsy results do not show HSIL lesions.
Purpose
The trabecular-orientated bionic hip stem was designed to mimic the natural force transmission through the femur in total hip arthroplasty, resulting in supposedly longer prosthesis ...survivability. The aim of this study was to compare the second-generation bionic hip stem to a standard uncemented hip stem.
Methods
A group of 18 patients (21 hips) who underwent total hip arthroplasty with a bionic stem (bionic group) was compared with a historic group of 12 patients (12 hips) treated with standard anatomic hip stem (control group). During the first year after the procedure, the densitometric measurements of the bone around the prosthesis were taken. Radiographic and clinical assessments were additionally performed preoperatively and at the three month, six month, one year and three year follow-ups in the bionic group.
Results
In the bionic group, one patient was revised for aseptic loosening and 16 patients (19 hips) were available to the final follow-up. A significant decrease of bone mineral density was found in Gruen zones 3, 4 and 5 in the bionic group, and in zone 7 in both groups. The bionic group had a significantly higher bone mineral density in Gruen zone 1 at the one year follow-up. At the final follow-up, all prostheses were radiologically stable in both groups.
Conclusions
Provided that a good implant position is achieved, comparable short-term results can be obtained using a bionic stem. Still, a decrease of bone mineral density in Gruen zone 7 occurred in both groups. Further studies are required to determine survivability of the bionic stem.
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