scholarly journals Comparative Evaluation of P16, Ki-67, and Shape-correlated Genes as Biomarkers for Cervical High-grade Squamous Intraepithelial Lesions

2020 ◽  
Author(s):  
hengzi Sun ◽  
Shuhong Li ◽  
Dongyan Cao ◽  
Jiaxin Yang ◽  
Peng Peng ◽  
...  
Keyword(s):  
Sensitivity And Specificity ◽  
Comparative Evaluation ◽  
Referral Rate ◽  
The Other ◽  
High Grade ◽  
Squamous Intraepithelial Lesions ◽  
Ki 67 ◽  
Intraepithelial Lesions ◽  
Dual Staining

Abstract Background:Colposcopy was referred in cases with severe abnormalities in co-testing. However, approximately 60%-80% patients did not receive proper benefits. Although p16/Ki67 dual staining reduced the referral rate, its sensitivity and specificity need to be enhanced. Methods:The expression of p16, Ki-67, SMAD3, YAP1, RELA were evaluated inthe colposcopy referral population. Results:The sensitivity and specificity of p16+ combined with Ki-67+ for predicting CIN2+ were 62.1% and 89.5%, respectively. p16+ combined with YAP1+ and/or RELA+ provided a sensitivity and specificity of 70.9% and 89.5%, respectively, while 72.8% and 86.4% were achieved by p16+ combined with YAP1+ and/or SMAD3+ and/or RELA+. In HPV16/18+ and LSIL subgroups, the sensitivity and specificity of p16+ combined with Ki-67+ for predicting CIN2+ were 67.7% and 87.6%, respectively, for the former group and 58.6%, 88.8%, respectively, for the latter group, whereas those of RELA alone were 76.9% and 90.5%, respectively, and 82.8% and 92.1%, respectively. p16+, YAP1+/RELA+ showed a better performance for predicting CIN2+ with a better sensitivity (86.7% vs. 52.2%, p=0.028) and considerable specificity (86.7% vs. 90.0%, p=0.486) in the other HPV+ combined with ASCUS groupthan were achieved by p16+ combined with Ki-67+. RELA+ and the combination of p16 and RELA/YAP1 also provided the Max AUC area. Conclusions:Our study shows that RELA and the combination of p16 and RELA/YAP1 achieved better sensitivity and specificity for detecting morphologically CIN2+ lesions.

scholarly journals Evaluation of HPV-Related Biomarkers in Anal Cytological Samples from HIV-Uninfected and HIV-Infected MSM

Pathogens ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 888
Author(s):  
Francesca Rollo ◽  
Alessandra Latini ◽  
Massimo Giuliani ◽  
Amalia Giglio ◽  
Maria Gabriella Donà ◽  
...  
Keyword(s):  
Linear Array ◽  
Anal Carcinoma ◽  
High Grade ◽  
Ki 67 ◽  
Hpv Dna ◽  
Cytological Abnormalities ◽  
Sex With Men ◽  
Anal Cancer Screening ◽  
Intraepithelial Lesions ◽  
Dual Staining

Men who have sex with men (MSM) harbor the highest risk for anal carcinoma, mainly caused by Human Papillomavirus (HPV). The use of HPV-related biomarkers in the screening for this neoplasia is still debated. We assessed the association between high-risk (hr)HPV DNA, HPV16/18 DNA, hrHPV E6/E7 mRNA, and p16/Ki-67 with cytological abnormalities (any grade) and high-grade intraepithelial lesions (HSIL) in HIV-uninfected and HIV-infected MSM. Overall, 150 cytological samples in PreservCyt (Hologic), with a negative to HSIL report, were analyzed for hrHPV DNA, hrHPV E6/E7 mRNA, and p16/Ki-67 using the Linear Array (Roche), Aptima (Hologic), and CINtec® PLUS (Roche) assays. In HIV-infected MSM, positivity for all the biomarkers significantly increased with the cytological grade. In both populations, the association of hrHPV E6/E7 mRNA and p16/Ki-67 positivity with HPV16 did not differ significantly compared to hrHPVs other than HPV16. In HIV-uninfected MSM, the odds of having an HSIL increased approximately six times for the p16/Ki-67 positive cases. In HIV-infected individuals, all the biomarkers showed a significant association with HSIL, except for hrHPV DNA, with the strongest association observed for p16/Ki-67. The odds of HSIL increased almost 21 times in those positive for this biomarker. Our results encourage further investigation on the use of p16/Ki-67 dual staining in anal cancer screening for HIV-uninfected and HIV-infected MSM.

scholarly journals p16/Ki-67 dual staining has a better accuracy than human papillomavirus (HPV) testing in women under 30 years old

2018 ◽  
Author(s):  
Laurențiu Pirtea ◽  
Cristina Secosan ◽  
Madalin Margan ◽  
Lavinia Moleriu ◽  
Oana Balint ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Sensitivity And Specificity ◽  
Pap Smear ◽  
High Rate ◽  
Low Grade ◽  
High Grade ◽  
Cervical Lesions ◽  
Ki 67 ◽  
Hpv Genotyping ◽  
Dual Staining

Due to a high rate of transient human papillomavirus (HPV) infection, HPV genotyping has a low specificity for high-grade cervical lesions, especially in young women. p16/Ki-67 dual immunohistochemical staining can also be used for the detection of oncogenic changes in cervical cells. Our aim was to compare the performance of p16/Ki-67 dual staining and HPV genotyping in the detection of high-grade cervical lesions in patients with atypical squamous cells of undetermined significance (ASCUS)/low-grade squamous intraepithelial lesion (LSIL) on Pap smear. We retrospectively analyzed 310 patients with ASCUS/LSIL on Pap smear, who underwent colposcopy. Among these, 161 patients with suspected lesions detected by colposcopy were referred to biopsy. HPV genotyping by LINEAR ARRAY HPV Genotyping Test (CE-IVD) and p16/Ki-67 dual staining by CINtec PLUS Cytology kit was performed prior to cervical biopsy. The overall sensitivity and specificity of HPV genotyping for the detection of cervical intraepithelial neoplasia (CIN) 2-3 was 79% and 72%, respectively in patients with ASCUS, and 85% and 64%, respectively in patients with LSIL. For p16/ki-67 test, sensitivity and specificity rate was 66% and 93%, respectively in ASCUS and 59% and 79%, respectively in LSIL group. The specificity of p16/Ki-67 staining was significantly higher in both groups in patients aged <30 years compared to patients >30 years old (p < 0.001). Our results showed that p16/Ki-67 dual staining has a higher specificity compared to HPV genotyping, especially in patients under 30 years old. This indicates the usefulness of p16/Ki-67 testing in the triage of patients with ASCUS/LSIL and <30 years old, prior to the referral to colposcopy and biopsy.

HPV16 genotype, p16/Ki-67 dual staining and koilocytic morphology as potential predictors of the clinical outcome for cervical low-grade squamous intraepithelial lesions

Cytopathology ◽  
2013 ◽  
Vol 26 (1) ◽  
pp. 10-18 ◽  
Author(s):  
D. Vrdoljak-Mozetič ◽  
M. Krašević ◽  
D. Verša Ostojić ◽  
S. Štemberger-Papić ◽  
R. Rubeša-Mihaljević ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Low Grade ◽  
Squamous Intraepithelial Lesions ◽  
Ki 67 ◽  
Intraepithelial Lesions ◽  
Dual Staining

Whole-Slide Imaging of Pap Cellblock Preparations Is a Potentially Valid Screening Method

2015 ◽  
Vol 59 (2) ◽  
pp. 187-200 ◽  
Author(s):  
Ossama Tawfik ◽  
Marilyn Davis ◽  
Susan Dillon ◽  
Laila Tawfik ◽  
Francisco J. Diaz ◽  
...  
Keyword(s):  
Sensitivity And Specificity ◽  
Low Grade ◽  
Adenocarcinoma In Situ ◽  
High Grade ◽  
Whole Slide Imaging ◽  
Squamous Intraepithelial Lesions ◽  
Squamous Cells ◽  
The Impact ◽  
Intraepithelial Lesions ◽  
Undetermined Significance

Objective: To date, the impact of digital imaging on routine cytology remains far from perfect. Cellblock (CB) preparations from Pap samples have been shown to be diagnostically valuable. We evaluated the validity of utilizing whole-slide imaging (WSI) prepared from Pap CBs as a screening tool. Study Design: A total of 1,110 CB slides prepared from residual Pap samples were analyzed - 563 normal, 282 atypical squamous cells of undetermined significance (ASCUS), 12 atypical squamous cells-cannot exclude high-grade squamous intraepithelial lesion, 188 low-grade squamous intraepithelial lesions (LSIL), 36 high-grade squamous intraepithelial lesions (HSIL), 25 atypical glandular cells of undetermined significance, 1 adenocarcinoma in situ, 2 invasive adenocarcinomas, and 1 squamous cell carcinoma. Virtual slides were obtained using the Aperio system. Test performance characteristics of liquid-based samples and WSI from CB samples were compared. Results: Average sensitivity and specificity of the five WSI reviewers was 58.3 and 85.1% for ASCUS, respectively, 54.1 and 93.9% for LSIL, and 51.8 and 98.8% for HSIL. Overall WSI sensitivity and specificity for detecting lesions was 82.1 and 86.2%, respectively. Agreement (kappa values) between WSI reviewers was 0.56 for ASCUS, 0.69 for LSIL, 0.67 for HSIL, and 0.74 for negative samples. Conclusions: WSI of CB preparations is a feasible method to achieve high-quality specimen preparations. It is as sensitive as liquid-based methods and appears to be highly specific for the detection of LSIL and HSIL.

scholarly journals Evaluation of p16/Ki-67 dual staining compared with HPV genotyping in anal cytology with diagnosis of ASC-US for detection of high-grade anal intraepithelial lesions

2019 ◽  
Vol 36 (3) ◽  
pp. 152
Author(s):  
Mojgan Devouassoux-Shisheboran ◽  
Maxime Pichon ◽  
Marie Joly ◽  
Frédérique Lebreton ◽  
Medhi Benchaïb ◽  
...  
Keyword(s):  
High Grade ◽  
Ki 67 ◽  
Hpv Genotyping ◽  
Anal Cytology ◽  
Intraepithelial Lesions ◽  
Dual Staining

P16 Immunostaining Can Eliminate Approximately 20% Inaccurate Diagnosis of Low-Grade Squamous Intraepithelial Lesions (SIL) in Cervical Biopsies

2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S25-S26
Author(s):  
O I Afolayan-Oloye ◽  
P Zhang
Keyword(s):  
Retrospective Study ◽  
Light Microscopy ◽  
Sensitivity And Specificity ◽  
Gold Standard ◽  
Low Grade ◽  
High Grade ◽  
Squamous Intraepithelial Lesions ◽  
Nuclear Atypia ◽  
Reactive Changes ◽  
Intraepithelial Lesions

Abstract Introduction/Objective Differentiating low-grade SIL from reactive changes on light microscopy has remained controversial. P16 immunostaining is widely accepted in high-grade SIL unlike in low-grade SIL. We focused on the use of p16 immunostaining in eliminating inaccurate diagnosis of low-grade SIL on light microscopy. Methods A retrospective study on 60 cervical biopsies results over a 2 year-period was conducted using 35 suspicious cases for low-grade SIL (bi-nucleation and some nuclear atypia) and 25 low suspicion cases (enlarged nuclei but nuclear atypia cannot differentiate from reactive changes). All cases were stained for p16, significant nuclear expression of p16 was determined as low- grade SIL. Results After p16 immunostaining, 30/35 (85%) cervical biopsies from the suspicious group were found to be truly positive for low-grade SIL while 5/35 (15%) biopsies negative for p16 immunostaining were regarded as reactive changes. In the low suspicious group, 7/25 (28%) were found to be positive for low-grade SIL and 18/25 (72%) biopsies were negative, favoring reactive changes. The overall percentage of all 60 biopsies that showed a changed diagnosis based on p16 immunostaining was 20% (5 were truly negative in the suspicious group and 7 were truly positive in the low suspicious group). Using a 2 x 2 table with p16 as a gold standard for all biopsies, sensitivity and specificity of light microscopy for low-grade SIL were only 81% and 78% respectively. Conclusion Our study showed that p16 immunostaining can also be utilized to eliminate inaccurate diagnosis of low- grade SIL up to 20% in cervical biopsies.

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