Usefulness of p16/Ki67 immunostaining in the triage of women referred to colposcopy

Ordi, Jaume; Sagasta, Amaia; Munmany, Meritxell; Rodríguez‐Carunchio, Leonardo; Torné, Aureli; Pino, Marta del

doi:10.1002/cncy.21366

Cited by 46 publications

(57 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…10,17 Recently, the combination of p16 and Ki67 detected by immunohistochemistry has been used in cytological samples to identify patients with high-grade cervical lesions. 18,19 In our study, the analysis of these biomarkers in biopsy material by immunohistochemistry showed that all were positive in a high proportion of the HSIL lesions, which is consistent with current evidence. 8,16,[20][21][22][23] Nevertheless, immunohistochemistry is not adequate for screening purposes.…”

Section: Discussionsupporting

confidence: 91%

mRNA biomarker detection in liquid-based cytology: a new approach in the prevention of cervical cancer

Pino

Svanholm-Barrie²,

Torné

et al. 2015

Modern Pathology

Self Cite

View full text Add to dashboard Cite

Several high-risk human papillomavirus (HPV)-induced cell biomarkers have been proposed as possible candidates to identify patients harboring high-grade squamous intraepithelial lesions (HSILs) of the uterine cervix. We aimed to determine the feasibility of the detection of the mRNA of six biomarkers in cervical smear specimens obtained by liquid-based cytology and to evaluate whether this approach might be useful in the identification of patients with HSIL. One-hundred and twenty three women referred to colposcopy in the Hospital Clinic of Barcelona were included in the study. After a thorough study, including Pap test, high-risk HPV testing (Hybrid Capture 2 test), and colposcopy with directed biopsy and/or endocervical curettage, 48 patients were diagnosed with HSIL, whereas 75 were classified as negative (n ¼ 28), or harboring low-grade SIL (n ¼ 47). CDKN2A/p16, BIRC5, MMP9, TOP2A, MCM5, and MKI67 mRNA expression was analyzed by reverse transcription quantitative polymerase chain reaction in liquid-based cytology after the Pap test and Hybrid Capture 2 performance. The tissue expression of these biomarkers was analyzed by immunohistochemistry in the biopsy material. One-hundred and thirteen out of 123 (92%) liquid-based cytology yielded adequate material for mRNA analysis. TOP2A was the most sensitive (97%) biomarker for the detection of HSIL and CDKN2A/p16 the most specific (78%). The combination of TOP2A and CDKN2A/p16 showed a sensitivity of 96% (95% confidence interval (CI): 88-99) and a specificity of 71% (95% CI: 55-82). In the immunohistochemistry analysis, all biomarkers showed a high sensitivity but low specificity for HSIL, except CDKN2A/p16 which had a sensitivity of 100% and a specificity of 63%. The combination of TOP2A and CDKN2A/p16 showed a sensitivity of 100% (95% CI: 91-100) and a specificity of 43% (95% CI: 32-55). The detection of mRNA of cell biomarkers in liquid-based cytology material is feasible. The combination TOP2A and CDKN2A/p16 has a good balance between sensitivity and specificity for the detection of women with HSIL. Modern Pathology (2015) 28, 312-320; doi:10.1038/modpathol.2014.106; published online 5 September 2014Screening programs based on cervical cytology (Pap test) have led to a decrease in the incidence and the mortality by cervical cancer. However, the efficacy of cytological screening is hampered by the suboptimal sensitivity and interobserver variability of the conventional Pap test. 1,2 Although the introduction of liquid-based cytology has not led to improvements in terms of relative sensitivity for the detection of cervical cancer precursors, 3 this technique has enabled the use of adjunctive tests that may help to reduce the rate of false-negative cytological results and add objectivity to the classical morphological evaluation.High-risk human papillomaviruses (HPV) are the causative agents of cervical cancer, and high-risk HPV testing has shown to improve the sensitivity of the Pap test to over 95%. 4,5 However, high-risk HPV tests have a lower specificity than...

show abstract

Section: Discussionsupporting

confidence: 91%

mRNA biomarker detection in liquid-based cytology: a new approach in the prevention of cervical cancer

Pino

Svanholm-Barrie²,

Torné

et al. 2015

Modern Pathology

Self Cite

View full text Add to dashboard Cite

show abstract

“…p16/Ki-67 dual staining performed in cytological samples has similar sensitivity to HPV testing for ASC-US and LSIL screening, and higher specificity [27,35]. This is also true for women positive for HPV but with negative cytology smears [25].…”

mentioning

confidence: 61%

Dual p16 and Ki-67 Expression in Liquid-Based Cervical Cytological Samples Compared to Pap Cytology Findings, Biopsies, and HPV Testing in Cervical Cancer Screening: A Diagnostic Accuracy Study

et al. 2018

View full text Add to dashboard Cite

Objective: Our objective was to verify the sensitivity and specificity of dual immunocytochemistry staining for p16 and Ki-67 in liquid-based samples (the “dual” assay) for cervical lesion screening, compared to biopsy findings and human papillomavirus (HPV) DNA molecular detection. Study Design: Sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values for the “dual immunocytochemistry assay” were calculated and compared to histopathological results and to high-risk HPV DNA detection in adult women or teenagers submitted to cervical cancer screening. Results: A total of 151 women were included. The majority (96.2%) of those with negative dual assay results had lower biopsy grades (p < 0.001). Women with cytology results suggestive of cervical cancer had positive dual immunocytochemistry assay results more frequently (p < 0.001), and these positive results were also significantly associated with biopsy findings (p < 0.001) and with high-risk genotype HPV infection (p = 0.007). Specificity and PPV for the dual assay were 0.972 (0.855–0.999) and 0.800 (0.284–0.995), respectively, and 1.000 (0.590–1.000) and 1.000 (0.631–1.000) for HPV detection. Conclusions: The dual immunocytochemistry assay had high specificity and PPV. It reveals a persistent HPV infection, avoiding the need for new tissue collections for biopsies or hybrid capture.

show abstract

“…The Department of Gynecology of our hospital has a very active referral Colposcopy Clinic 24. Consequently, the series included 157 biopsies or excisions of the uterine cervix from patients referred to colposcopy because of an abnormal Pap smear.…”

Section: Methodsmentioning

confidence: 99%

Validation of whole slide imaging in the primary diagnosis of gynaecological pathology in a University Hospital

et al. 2014

Self Cite

View full text Add to dashboard Cite

AimsExperience in the use of whole slide imaging (WSI) for primary diagnosis in pathology is very limited. We aimed to determine the accuracy of interpretation of WSI compared with conventional light microscopy (CLM) in the diagnosis of routine gynaecological biopsies.MethodsAll gynaecological specimens (n=452) received over a 2-month period at the Department of Pathology of the Hospital Clinic of Barcelona were analysed blindly by two gynaecological pathologists, one using CLM and the other WSI. All slides were digitised in a Ventana iScan HT (Roche diagnostics) at 200×. All discrepant diagnoses were reviewed, and a final consensus diagnosis was established. The results were evaluated by weighted κ statistics for two observers.ResultsThe level of interobserver agreement between WSI and CLM evaluations was almost perfect (κ value: 0.914; 95% CI 0.879 to 0.949) and increased during the study period: κ value 0.890; 95% CI 0.835 to 0.945 in the first period and 0.941; 95%; CI 0.899 to 0.983 in the second period. Major discrepancies (differences in clinical management or prognosis) were observed in 9 cases (2.0%). All discrepancies consisted of small lesions (8 high grade squamous intraepithelial lesions of the uterine cervix, one lymph node micrometastasis of an ovarian carcinoma) underdiagnosed or missed in the WSI or the CLM evaluation. Discrepancies with no or minor clinical relevance were identified in 3.8% of the biopsies. No discrepancy was related to the poor quality of the WSI image.ConclusionsDiagnosis of gynaecological specimens by WSI is accurate and may be introduced into routine diagnosis.

show abstract

Usefulness of p16/Ki67 immunostaining in the triage of women referred to colposcopy

Abstract: BACKGROUND: This study compared the performance of p16/Ki67 dual-staining and human papillomavirus (HPV) testing in women referred to colposcopy and sought to determine the usefulness of a morphological evaluation of the double-

Cited by 46 publications

References 37 publications

mRNA biomarker detection in liquid-based cytology: a new approach in the prevention of cervical cancer

mRNA biomarker detection in liquid-based cytology: a new approach in the prevention of cervical cancer

Dual p16 and Ki-67 Expression in Liquid-Based Cervical Cytological Samples Compared to Pap Cytology Findings, Biopsies, and HPV Testing in Cervical Cancer Screening: A Diagnostic Accuracy Study

Validation of whole slide imaging in the primary diagnosis of gynaecological pathology in a University Hospital

Contact Info

Product

Resources

About