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

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

Bosnian Journal of Basic Medical Sciences ◽

10.17305/bjbms.2018.3560 ◽

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.

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

10.21203/rs.3.rs-33881/v1 ◽

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.

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8. Human papillomavirus mRNA testing for the detection of anal high-grade squamous intraepithelial lesions in HIV-positive men who have sex with men

Sexual Health ◽

10.1071/shv10n6ab8 ◽

2013 ◽

Vol 10 (6) ◽

pp. 573

Author(s):

Elena Sendagorta Cudós ◽

Maria P. Romero Gomez ◽

Beatriz Hernandez Novoa ◽

Ander Mayor ◽

Jose I. Bernardino De La Serna ◽

...

Keyword(s):

Predictive Value ◽

Screening Program ◽

University Hospital ◽

High Grade ◽

Squamous Intraepithelial Lesions ◽

Cross Sectional ◽

Hpv Dna ◽

Hpv E6 ◽

Anal Cytology ◽

Intraepithelial Lesions

Background Currently, screening for anal high-grade squamous intraepithelial lesions (HSIL) relies on anal cytology and high-resolution anoscopy (HRA). Since this approach has limited sensitivity and specificity for detecting anal HSIL, there is increasing interest in the role of biomarkers for predicting anal HSIL. The aim of this study is to evaluate the diagnostic accuracy of HPV E6/E7-mRNA expression for the detection of anal HSIL in MSM HIV-infected patients, in comparison to DNA-HR-HPV and anal cytology. Methods: This cross-sectional screening study included 101 MSM followed at the HIV-unit of La Paz University Hospital. Intra-anal swabs from patients participating in a screening program including cytology, HRA and histology were analysed. HR-HPV-DNA detection was performed by means of the CLART HPV2 assay (GENOMICA SAU.). E6/E7-mRNA detection of HR-HPV types 16, 18, 31, 33 and 45 was performed using the NucliSENS-EasyQ assay (BioMérieux, Marcy l’Etoile, France). Results: HR-HPV DNA and HPV E6/E7 mRNA were detected in 82% and 57% of the anal smears, respectively. Anal cytology screening was abnormal in 70.3%. For the detection of HSIL sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 71.7%, 55.6%, 57.9%, and 69.8% for E6/E7-mRNA testing, respectively, compared with 97.9%, 31.5%, 55.4% and 94.4%, respectively, for HR-HPV DNA testing and 83%, 40.7%, 54.9%, 73.3%, respectively, for cytology testing. Conclusions: In comparison with the other tests, the NucliSENS EasyQ HPV assay yielded a lower clinical sensitivity but a higher clinical specificity and PPV for the detection of anal HSIL in MSM HIV-infected patients.

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36. Anal cytology and HPV genotyping in women with lower genital tract neoplasia

Sexual Health ◽

10.1071/shv10n6ab36 ◽

2013 ◽

Vol 10 (6) ◽

pp. 587 ◽

Cited By ~ 1

Author(s):

Katina Robison ◽

Beth Cronin ◽

Christine Luis ◽

Paul DiSilvestro ◽

Melissa Clark

Keyword(s):

High Risk ◽

Genital Tract ◽

Exposed Group ◽

Control Group ◽

High Grade ◽

Hpv Genotyping ◽

Lower Genital Tract ◽

Anal Cytology ◽

History Of ◽

High Risk Hpv

Objective To compare the prevalence of abnormal anal cytology and high-risk HPV among women with a recent history of HPV-related genital neoplasia to women without a history of HPV-related genital neoplasia. Methods: A cross-sectional pilot study was performed. Women with a history of high-grade cervical, vulvar, or vaginal dysplasia or cancer within the past 2 years were eligible for the exposed group. Women without a history of high-grade anogenital dysplasia or cancer were eligible for the control group. Anal cytology and HPV genotyping were performed after informed consent was obtained. Results: 127 women were enrolled in the exposed group and 45 in the control group. The control group was slightly older and less likely to be current smokers. There was no difference between groups in history of anal intercourse. Forty-four per cent of the exposed group had abnormal anal cytology compared with 21.6% of the control group (P = 0.03). High-risk HPV was detected in the anal canal of 6 in the exposed group compared with none in the control group (P = 0.2). Fourteen per cent of the anal cytology results were read as insufficient in both groups. HPV results were insufficient in 29.2% of exposed versus 43.5% of control (P = 0.2). Conclusions: Women with a history of lower genital tract dysplasia are more likely to have a positive anal cytology result compared with women without a history. Additional information is needed to determine the best method of anal cancer screening among women with a history of lower genital tract dysplasia.

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HPV genotyping and p16/Ki-67 test significantly improve detection rate of high-grade cervical squamous intraepithelial lesion

Archives of Medical Science ◽

10.5114/aoms.2018.80697 ◽

2020 ◽

Vol 16 (1) ◽

pp. 87-93

Author(s):

Piotr Lewitowicz ◽

Anna Nasierowska-Guttmejer ◽

Wojciech Rokita ◽

Olga Adamczyk-Gruszka ◽

Stanisław Gluszek ◽

...

Keyword(s):

Detection Rate ◽

High Grade ◽

Squamous Intraepithelial Lesion ◽

Ki 67 ◽

Hpv Genotyping ◽

Intraepithelial Lesion ◽

Cervical Squamous Intraepithelial Lesion

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Abstract 1123: Simultaneous p16/ki-67 expression in detection of high-grade squamous intraepithelial lesions, in women with ASC in cervical smears

10.1158/1538-7445.am2020-1123 ◽

2020 ◽

Author(s):

Lia Barrios ◽

Luis Alvis ◽

Ines Benedetti

Keyword(s):

High Grade ◽

Squamous Intraepithelial Lesions ◽

Ki 67 ◽

Cervical Smears ◽

Intraepithelial Lesions

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Biomarker Expression in Multifocal Vulvar High-Grade Squamous Intraepithelial Lesions

Cancers ◽

10.3390/cancers13225646 ◽

2021 ◽

Vol 13 (22) ◽

pp. 5646

Author(s):

Nikki B. Thuijs ◽

Willemijn A. M. Schonck ◽

Linde L. J. Klaver ◽

Guus Fons ◽

Marc van Beurden ◽

...

Keyword(s):

Dna Methylation ◽

Expression Profiles ◽

High Grade ◽

Squamous Intraepithelial Lesion ◽

Predictive Diagnostics ◽

Ki 67 ◽

Intraepithelial Lesion ◽

Prospective Longitudinal ◽

Intraepithelial Lesions ◽

Six Genes

In patients with high-grade squamous intraepithelial lesion (HSIL) of the vulva, the presence of multiple lesions, called multifocal HSIL, is common. The aim of this exploratory study was to investigate biomarker expression profiles in multifocal HSIL. In total, 27 lesions from 12 patients with high-risk human papillomavirus (HPV)-positive multifocal HSIL were tested for HPV genotype, expression of p16INK4a and Ki-67, and DNA methylation of six genes. HPV16 was found most commonly in 21 (77.8%) HSILs. In two (16.4%) patients, HPV genotype differed between the lesions. All lesions demonstrated diffuse p16INK4a staining, of which three (11.1%) were combined with patchy staining. One patient (8.3%) demonstrated markedly different DNA methylation levels between lesions. Generally, heterogeneity in methylation profiles was observed between different patients, even when other biomarkers showed similar expression. In conclusion, this study is the first to demonstrate heterogeneity of individual lesions in patients with multifocal HSIL. The studied biomarkers have the potential to refine prognostic and predictive diagnostics. Future prospective, longitudinal studies are needed to further explore the potential of a biomarker profile for management of patients with multifocal HSIL.

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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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38. Anal cancer screening in HIV primary care: uptake and outcomes

Sexual Health ◽

10.1071/shv10n6ab38 ◽

2013 ◽

Vol 10 (6) ◽

pp. 588 ◽

Cited By ~ 5

Author(s):

Irving E. Salit ◽

Sandra Blitz ◽

Evan Collins ◽

Banita Aggarwal ◽

Janet Raboud ◽

...

Keyword(s):

Primary Care ◽

Cancer Screening ◽

Anal Cancer ◽

High Grade ◽

Anal Cytology ◽

Hiv Primary Care ◽

Anal Cancer Screening ◽

Primary Care Practices ◽

To Receive ◽

Intraepithelial Lesions

Background Anal cytology (Pap tests) plus high-resolution anoscopy (HRA) as required are felt to be the optimal approach to anal cancer screening. We present preliminary results from STANDOUT, a study of acceptability and outcomes of anal cancer screening of HIV+ MSM in primary care practices. Methods: All previously unscreened HIV+ MSM from 9 HIV primary care practices, were invited by email or letter to receive anal cancer screening. Responders had anal cytology done at specially arranged or routine clinic visits. Those with high-grade squamous intraepithelial lesions (HSIL) on anal cytology were offered HRA to assess for anal intraepithelial neoplasia (AIN). Those with AIN 2/3 on biopsy were randomised to receive trichloroacetic acid (TCA) or infrared coagulator (IRC) treatments. Results: 1733 patients were invited and 921 (53%) agreed to have anal cytology done. Among those screened, 3 had unsatisfactory samples; 596 (65%) had normal cytology, 253 (27%) had low-grade squamous intraepithelial lesions (LSIL) and 69 (7.5%) had HSIL. HRA results are available in 64: 41 (64%) had histologic high-grade disease (29 had AIN2 and 12 had AIN3). Those with AIN 2/3 were randomised to receive treatment with TCA (16 patients) or IRC (18 patients). Treatment successes at 3 months were 6 of 15 patients for TCA (40%) and 11 of 16 patients for IRC (69%). Conclusions: In this sample of HIV+ MSM, about half of those invited for anal cancer screening agreed to have it done. Most with HSIL had histological high-grade disease and were treated. IRC was more successful than TCA at ablating high-grade disease.

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