Dual staining for p16/Ki‐67 to detect high‐grade cervical lesions: Results from the Screening Triage Ascertaining Intraepithelial Neoplasia by Immunostain Testing study

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.

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Abnormal colposcopic images in patients with preinvasive cervical lesions

Journal of Health Sciences ◽

10.17532/jhsci.2013.71 ◽

2013 ◽

Vol 3 (2) ◽

pp. 98-102

Author(s):

Adnan Babović ◽

Dženita Ljuca ◽

Gordana Bogdanović ◽

Lejla Muminhodžić

Keyword(s):

Intraepithelial Neoplasia ◽

Control Group ◽

Low Grade ◽

High Grade ◽

Cervical Lesions ◽

Cytological Examination ◽

Chi Square ◽

Chi Square Test ◽

Intraepithelial Lesion ◽

Experimental Group

Introduction: The objective of the study was to determine frequency and to compare frequency of the abnormal colposcopic images in patients with low and high grade pre-invasive lesions of cervix.Methods: Study includes 259 patients, whom colposcopic and cytological examination of cervix was done. The experimental group of patients consisted of patents with pre-invasive low grade squamousintraepithelial lesion (LSIL) and high grade squamous intraepithelial lesion (HSIL), and the control group consisted of patients without cervical intraepithelial neoplasia (CIN).Results: In comparison to the total number of satisfactory fi ndings (N=259), pathological findings were registered in N=113 (43.6 %) and abnormal colposcopic fi ndings in N=128 (49.4%). The study did notinclude patients with unsatisfactory fi nding N=22 (8.5%). Abnormal colposcopic image is present most frequently in older patients but there are no statistically important difference between age categories(Pearson Chi-Square 0.47, df -3, p=0.923). Frequency of abnormal colposcopic fi ndings (N=128) is the biggest in pathological cytological (N=113) and HSIL 58 (45.3%), LSIL 36 (28.1%). There is statisticallysignifi cant difference in frequency of abnormal colposcopic images in patients with low-grade in comparison to patients with high-grade pre-invasive cervix lesions (Chi-Square test, Pearson Chi-Square 117.14,df-12 p<0.0001).Conclusion: Thanks to characteristic colposcopic images, abnormal epithelium is successfully recognized, but the severity grade of intraepithelial lesion cannot be determined.

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p16/Ki67 dual staining improves the detection specificity of high-grade cervical lesions

Journal of Obstetrics and Gynaecology Research ◽

10.1111/jog.13760 ◽

2018 ◽

Vol 44 (11) ◽

pp. 2077-2084 ◽

Cited By ~ 1

Author(s):

Ruiyi Zhang ◽

Xuefei Ge ◽

Ke You ◽

Yanli Guo ◽

Hongyan Guo ◽

...

Keyword(s):

High Grade ◽

Cervical Lesions ◽

Detection Specificity ◽

Dual Staining

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The Role of Early Colposcopy in the Management of Females with First Episode Anogenital Warts

International Journal of STD & AIDS ◽

10.1177/095646249400500511 ◽

1994 ◽

Vol 5 (5) ◽

pp. 343-345 ◽

Cited By ~ 2

Author(s):

K A Ward ◽

J R Houston ◽

B E Lowry ◽

R D Maw ◽

W W Dinsmore

Keyword(s):

Intraepithelial Neoplasia ◽

Hpv Infection ◽

Cervical Cytology ◽

First Episode ◽

Low Grade ◽

High Grade ◽

Anogenital Warts ◽

Cervical Smear ◽

Cervical Lesions ◽

Increased Risk

212 females attending a genitourinary medicine (GUM) clinic with first episode anogenital warts were screened by cervical cytology and colposcopy/histology for the presence of cervical epithelial abnormalities in keeping with infection by the human papillomavirus (HPV infection) and/or cervical intraepithelial neoplasia (CIN). The prevalence of cervical epithelial abnormalities detected by cervical cytology alone was 32%, rising to 56% after colposcopic examination. However, the majority of cervical lesions detected by colposcopy alone were of low grade (HPV infection and/or CIN I). Histologically confirmed high grade cervical lesions (CIN II or CIN III) were detected more frequently in those females in whom cervical cytological examination indicated dyskaryosis in keeping with any grade of CIN, compared to females without dyskaryotic changes on cervical smear ( P<0.05, chi-squared test with Yates' correction). Early colposcopy is indicated for females with anogenital warts in the presence of a cervical smear showing dyskaryosis in keeping with any grade of CIN, because of the statistically significant increased risk of detecting a potentially progressive high grade cervical lesion. In females without dyskaryotic changes on cervical smear, the value of early colposcopy is uncertain and warrants larger more long-term trials.

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Ki-67 expression in anal intraepithelial neoplasia in AIDS

Sao Paulo Medical Journal ◽

10.1590/s1516-31802001000300007 ◽

2001 ◽

Vol 119 (3) ◽

pp. 119-121 ◽

Cited By ~ 7

Author(s):

Edenilson Eduardo Calore ◽

Carmen Ruth Manzione ◽

Sidney Roberto Nadal ◽

Maria José Cavalieri ◽

Nilda Maria Perez Calore ◽

...

Keyword(s):

Lower Layer ◽

Intraepithelial Neoplasia ◽

Cell Counting ◽

Biological Behavior ◽

Low Grade ◽

High Grade ◽

Ki 67 ◽

Staining Techniques ◽

The Mean ◽

Group 2

CONTEXT: AIDS is one of the most important risk factors for progression and recurrence of anogenital condyloma. In a previous work, we observed that patients with warts and high-grade AIN (HAIN) had recurrences more frequently than did patients with warts without AIN. The mechanisms of this increased incidence of high-grade lesions in AIDS are not known. OBJECTIVE: We studied the expression of the proliferative marker Ki-67 by immunohistochemical methods, in specimens of anal condyloma from HIV+ patients to clarify whether its expression can be associated to the grade of AIN. DESIGN: A retrospective study of hiltological specimens. SETTING: University referral unit. SAMPLE: 34 patients were divided into two groups: (1) condylomas with low grade AIN (LAIN), with 25 patients; and (2) condylomas with HAIN, with 9 patients. In this latter group we examined two areas: 2A (HAIN area) and 2B (LAIN area). MAIN MEASUREMENTS: The immunohistochemical reaction for Ki-67 was done on histological sections. Slices were lightly stained with hematoxylin, to help us in Ki-67 positive cell counting. The percentage of Ki-67 marked nuclei was calculated. We applied one-way variance analysis for statistics. RESULTS: The mean number of Ki-67 positive cells in group 1 was 19.68 ± 10.99; in group 2 (area A) it was 46.73 ± 10.409; and in area B it was 36.43 ± 14.731. There were statistical differences between groups 1 and 2A and between groups 1 and 2B. Ki-67 positive cells predominated in the lower layer in LAIN. Positive Ki-67 cells were found in all layers in group 2A, and in group 2B they predominated in the two lower or in all layers of the epithelium. CONCLUSIONS: Our results suggest that LAIN areas (using routine staining techniques) in HAIN can have a biological behavior more similar to HAIN.

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

Pathogens ◽

10.3390/pathogens10070888 ◽

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.

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The Accuracy of Anal Swab–Based Tests to Detect High-Grade Anal Intraepithelial Neoplasia in HIV-Infected Patients: A Systematic Review and Meta-analysis

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz191 ◽

2019 ◽

Vol 6 (5) ◽

Cited By ~ 3

Author(s):

Fernando Dias Gonçalves Lima ◽

Janine D Viset ◽

Mariska M G Leeflang ◽

Jacqueline Limpens ◽

Jan M Prins ◽

...

Keyword(s):

Anal Cancer ◽

Predictive Value ◽

Dna Detection ◽

Intraepithelial Neoplasia ◽

Anal Intraepithelial Neoplasia ◽

Hiv Positive ◽

High Grade ◽

Ki 67 ◽

Hpv Dna ◽

Anal Swab

Abstract Background The incidence of high-risk human papillomavirus (HR-HPV)–induced anal cancer is increasingly problematic among HIV-positive patients. Anal cancer is preceded by precursor lesions, anal intraepithelial neoplasia (AIN). AIN detection requires high-resolution anoscopy, a cumbersome and time-consuming procedure. We aggregated evidence on anal swab–based tests to detect AIN in HIV-positive patients. Methods We searched MEDLINE and EMBASE for cross-sectional studies on AIN detection with anal cytology, HR-HPV DNA detection, HPV E6/E7 mRNA analysis, and P16INK4a and Ki-67 immunostaining. Summary estimates of sensitivity and specificity were calculated using bivariate logistic regression. Cytology was reported using the terms squamous intra-epithelial lesion (SIL) for AIN and high-grade SIL (HSIL) for high-grade AIN (HGAIN). Results We included 22 studies. Using cytology with a cutoff of any SIL to detect HGAIN, we detected a sensitivity of 82% (95% CI, 74%–87%) and specificity of 45% (95% CI, 44%–66%); with the cutoff of HSIL, the sensitivity was 44% (95% CI, 45%–67%) and the specificity was 79% (95% CI, 69%-87%). The sensitivity of HPV DNA to detect HGAIN was 91% (95% CI, 82%–95%) and the specificity was 27% (95% CI, 21%–33%). For MSM, the positive predictive value (PPV) of cytology with a cutoff of any SIL was 36% (95% CI, 23%–50%) and the negative predictive value (NPV) was 87% (95% CI, 78%–93%), whereas cytology with a cutoff of HSIL had a PPV of 62% (95% CI, 50%–73%) and an NPV of 78% (95% CI, 65%–87%). The PPV of HR-HPV DNA detection was 37% (95% CI, 20%–57%) and the NPV was 87% (95% CI, 79%–93%). Conclusions Given its sensitivity, cytology with a cutoff of any SIL could be considered as a triaging method, whereas cytology with a cutoff of HSIL had better specificity and could be used for quality assurance. HR-HPV DNA detection had poor specificity and PPV, making it unsuitable for triage.

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HER2 Status in Premalignant, Early, and Advanced Neoplastic Lesions of the Stomach

Disease Markers ◽

10.1155/2015/234851 ◽

2015 ◽

Vol 2015 ◽

pp. 1-10 ◽

Cited By ~ 16

Author(s):

A. Ieni ◽

V. Barresi ◽

L. Rigoli ◽

R. A. Caruso ◽

G. Tuccari

Keyword(s):

Current Knowledge ◽

Intraepithelial Neoplasia ◽

Disease Recurrence ◽

Her2 Status ◽

Her2 Overexpression ◽

Low Grade ◽

High Grade ◽

Gastric Lesions ◽

Ki 67 ◽

Gastric Type

Objectives. HER2 expression in gastric cancer (GC) has received attention as a potential target for therapy with Trastuzumab. We reviewed the current knowledge on HER2 status in premalignant gastric lesions and in early (EGC) and advanced (AGC) GC to discuss the possible pathogenetic and prognostic roles of HER2 overexpression in GC.Results. HER2 overexpression was documented in gastric low-grade (LG) and high-grade intraepithelial neoplasia (HG-IEN), with higher frequency in gastric type dysplasia. HER2 overexpression was significantly associated with disease recurrence and poor prognosis in EGC representing an independent risk factor for lymph node metastases. HER2 overexpression was more frequent in AGC characterized by high grade, advanced stage, and high Ki-67 labeling index. The discordance in HER2 status was evidenced between primitive GC and synchronous or metachronous metastases.Conclusions. HER2 overexpression in premalignant gastric lesions suggests its potential involvement in the early steps of gastric carcinogenesis. The assessment of HER2 status in EGC may be helpful for the identification of patients who are at low risk for developing nodal metastases. Finally, the possible discordance in HER2 status between primary GC and its synchronous metastases support routine assessment of HER2 both in the primary GC and in its metastatic lesions.

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Expression of nuclear Ki-67 antigen in prostatic high grade intraepithelial neoplasia and prostatic carcinoma

Vojnosanitetski pregled ◽

10.2298/vsp0705325j ◽

2007 ◽

Vol 64 (5) ◽

pp. 325-330 ◽

Cited By ~ 1

Author(s):

Ljubinka Jankovic-Velickovic ◽

Biljana Djordjevic ◽

Gorana Rancic ◽

Goran Marjanovic

Keyword(s):

Gleason Score ◽

Proliferative Activity ◽

Prostatic Carcinoma ◽

Prognostic Significance ◽

Intraepithelial Neoplasia ◽

High Grade ◽

Proliferating Cells ◽

Ki 67 ◽

Prostatic Epithelium ◽

Progressive Disorder

Background/Aim. Prostatic intraepithelial high grade neoplasia (PINHG) is accepted as preneoplastic lesion in prostatic carcinoma. One of the fundamental events in early oncogenesis is the disruption of proliferative activity. One of the numerous regulatory proteins is Ki-67 expressed in all proliferating cells. Index Ki-67 is considered to have prognostic significance. The aim of the study was to compare the level of proliferation in hyperplastic epithelium, prostatic carcinoma (Gleason score > 6) and PINHG. Methods. Micromorphological examination was done in 85 patients. Pathohistological analysis was performed on standard histologic specimens with the estimation of Gleason score and the presence of PINHG in its surroundings. Nuclear proliferative activity was analyzed immunohistochemically in 19 cases, using a monoclonal anti-Ki-67 antibody. Results. PINHG was found in prostatic carcinoma surrounding in 30% of the patients. In hyperplastic epithelia Ki-67 proliferative activity was 1,08, in PINHG 2,25 (p < 0,05), while in prostatic cancer, Ki-67 index was 17,64. Proliferative activity in prostatic carcinoma was significantly higher than in PINHG (p < 0,001) and hyperplasia (p < 0,001). Conclusion. This study confirmed that high grade PIN lesion predominately appears in the surrounding of poor or moderately differentiated prostate carcinoma, and that it represents progressive disorder of proliferation in preneoplastic and neoplastic prostatic epithelium. .

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Immunocytochemical expression of Ki-67/p16 in normal, atypical, and neoplastic cells in urine cytology using BD SurePath™ as preparation method

CytoJournal ◽

10.4103/cytojournal.cytojournal_9_19 ◽

2019 ◽

Vol 16 ◽

pp. 26 ◽

Cited By ~ 1

Author(s):

Kirsten Margrethe Østbye ◽

Mette Kristin Pedersen ◽

Torill Sauer

Keyword(s):

Urine Cytology ◽

Low Grade ◽

High Grade ◽

Ki 67 ◽

Additional Information ◽

Additional Marker ◽

Dual Positivity ◽

Normal Controls ◽

Dual Staining

Objective: The objective of this study was to investigate the expression of Ki-67/p16 in urothelial cells in cytological material. Materials and Methods: There were 142 urines including normal controls, anonymous rest urine, controls after treatment for urothelial carcinoma (UC) and newly diagnosed UC. Immunocytochemistry for ki-67/p16 dual staining kit was performed on all specimens. Results: Eight high-grade UC and six anonymous specimens showed dual positivity. None of the low-grade UC or the control specimens after treated UC showed dual staining. Fifteen of 84 (17.8%) symptomatic cases were negative for both markers, and 59/84 (70.2%) showed positivity for both but not dual staining. Twenty-seven of 84 cases were positive for either Ki-67 (n = 22) or p16 (n = 5). Normal controls and benign specimens were negative for p16. Conclusions: Co-expression of p16/Ki-67 in the same cells was found in 16.6% of the cases. All were high grade, and co-expression seems to have limited practical impact as an additional marker in urine cytology. Any positivity for p16 alone strongly indicates malignancy. Negative p16 accompanied by a positive Ki-67 rate at 5% or more could be considered as an additional marker for further clinical follow-up. Both markers, co-expressed and separate, can give additional information in follow-up patients after treatment for UC.

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