Usefulness of liquid-based cytology specimens for the immunocytochemical study of p16 expression and human papillomavirus testing

Yoshida, Tomomi; Fukuda, Toshio; Sano, Takaaki; Kanuma, Tatsuya; Owada, N; Nakajima, Takashi

doi:10.1002/cncr.20046

Cited by 84 publications

(69 citation statements)

References 31 publications

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“…Sano et al 14,15 reported that the status of p16 immunoreactivity may help to differentiate low-risk HPV infections from high-risk or intermediate-risk HPV infections. We previously reported that immunochemical detection of p16 was more sensitive and specific than clarification of the HPV status in cervical lesions by using a liquid-based method as well as tissue samples, 5 thereby suggesting that p16 should represent a good biomarker for primary screening of cervical cytology. Klaes et al 13 also reported that p16 expression can be used to identify dysplastic and cancer cells.…”

Section: Discussionmentioning

confidence: 99%

“…We previously revealed that p16 protein (p16) immunostaining in liquid-based smears, with simultaneously obtained biopsies, was a useful new prognostic biomarker. 5 The CDKN2A gene product, p16, has been found to be overexpressed in cervical preneoplastic and neoplastic lesions where high-risk HPV subtypes exist. 6 In cervical carcinogenesis, oncogenes E6 and E7 of HPV cause inactivation of the tumor-suppressor gene-protein products p53 and Rb, thereby resulting in disruption of the p53 and Rb pathways at the G1 checkpoint, respectively.…”

mentioning

confidence: 99%

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Immunochemical analysis of HPV L1 capsid protein and p16 protein in liquid-based cytology samples from uterine cervical lesions

Sano

Kanuma

et al. 2008

Cancer

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Immunochemical analysis of HPV L1 capsid protein and p16 protein in liquid-based cytology samples from uterine cervical lesions

Sano

Kanuma

et al. 2008

Cancer

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“…The introduction of a liquid-based medium for collection of cytologic specimens has allowed other molecular techniques to be evaluated more easily as adjunctive or triage tests (12). The aim of this study was to compare directly the sensitivity and specificity of several tests from the same sample for the detection of high-grade cervical intraepithelial neoplasia (CIN) in a population referred to colposcopy because of abnormal cytology.…”

Section: Introductionmentioning

confidence: 99%

Comparison of Predictors for High-Grade Cervical Intraepithelial Neoplasia in Women with Abnormal Smears

Szarewski

Ambroisine

Cadman

et al. 2008

Cancer Epidemiology, Biomarkers &Amp; Prevention

212

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Background: The detection of high-risk human papillomavirus (HPV) DNA provides higher sensitivity but lower specificity than cytology for the identification of high-grade cervical intraepithelial neoplasia (CIN). This study compared the sensitivity and specificity of several adjunctive tests for the detection of high-grade CIN in a population referred to colposcopy because of abnormal cytology. Methods: 953 women participated in the study. Up to seven tests were carried out on a liquid PreservCyt sample: Hybrid Capture II (Digene), Amplicor (Roche), PreTect HPV-Proofer (NorChip), APTIMA HPV assay (Gen-Probe), Linear Array (Roche), Clinical-Arrays (Genomica), and CINtec p16INK4a Cytology (mtm Laboratories) immunocytochemistry. Sensitivity, specificity, and positive predictive value (PPV) were based on the worst histology seen on either the

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“…6,10 The ploidy of epithelial cells and the immunohistochemical detection of expression of genetic markers can be assessed with an intact morphological background by immunocytochemistry and in situ hybridization enhancing identification of dysplastic cells. 8,9,35,36 For instance, p16 immunohistochemical study on liquid-based cytology has been reported to be particularly hopeful in detection of cancer cells and their precursors although there still exist limitations in its application. 6,36 Further exploration of novel biomarkers for identifying cervical cancers and their precursors is still an ongoing process.…”

Section: Novel Markers For Cervical Cytologymentioning

confidence: 99%

“…8,9,35,36 For instance, p16 immunohistochemical study on liquid-based cytology has been reported to be particularly hopeful in detection of cancer cells and their precursors although there still exist limitations in its application. 6,36 Further exploration of novel biomarkers for identifying cervical cancers and their precursors is still an ongoing process.…”

Section: Novel Markers For Cervical Cytologymentioning

confidence: 99%

P634A4 and TAp73 immunocytochemistry in liquid-based cervical cytology—potential biomarkers for diagnosis and progress prediction of cervical neoplasia

Cheung

Tsun

et al. 2010

Modern Pathology

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P63 and p73 are two homologues of the important tumor suppressor gene p53. In this study, we investigated p63 and p73 expression by immunocytochemistry using antibodies for TAp73 and p634A4 isoforms in 91 highgrade and 107 low-grade squamous intraepithelial lesions, 212 atypical squamous cells of undetermined significance, 9 squamous cell carcinomas and 63 normal samples from an Asian screening population together with 47 hospital samples of carcinomas. There was significant correlation between the TAp73 and p634A4 indices (Po0.0001). Significantly, higher TAp73 and p634A4 indices were found in high-grade lesions or carcinoma when compared with atypical squamous cells and low-grade lesions (Po0.0001). Among atypical squamous cells, p634A4 indices of cases that subsequently progressed to low-grade (P ¼ 0.031) or high-grade lesions (P ¼ 0.006) were significantly higher than those that did not. For atypical squamous cells positive for high-risk human papillomavirus (HPV) as detected by Digene (61%), cases with high p634A4 index were still more likely to have subsequent high-grade lesions detected (P ¼ 0.016). Among low-grade lesions, significantly higher TAp73 (P ¼ 0.038) was found in cases that subsequently progressed to high-grade lesions. There was significant correlation between presence of high-risk HPV and p634A4 index (P ¼ 0.01). In summary, p63 and p73 immunocytochemistry are potential good markers for detection of carcinoma and high-grade lesions in cervical cytology samples and for triage management of women with atypical squamous cells and low-grade Cervical cytology screening is effective in the prevention of cervical cancer by detecting asymptomatic cervical cancer and its precursors although there is limitation in its sensitivity and specificity. 1 Among cytological abnormalities detectable in a screening population, atypical squamous cells of undetermined significance (ASC-US) and low-grade squamous intraepithelial lesion (LSIL), especially the former, are the most common diagnostic categories. [2][3][4] Both were associated with a higher possibility of subsequent development of cervical cancer when compared with women with negative cytology. 3 Colposcopic examination of all such cases poses significant demand on the community resources. To improve the efficiency of cervical cancer screening, human papillomaviruses (HPV) DNA testing has been introduced for the triage of women with ASC-US and for primary screening. 5,6 Although HPV test shows high sensitivity, additional markers are necessary to improve the specificity of identifying cervical cancers or high-grade precursors. [7][8][9][10][11] It is also necessary to discover adjunct markers for management of LSIL as HPV testing is not so effective in triage management of LSIL.

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Usefulness of liquid-based cytology specimens for the immunocytochemical study of p16 expression and human papillomavirus testing

Cited by 84 publications

References 31 publications

Immunochemical analysis of HPV L1 capsid protein and p16 protein in liquid-based cytology samples from uterine cervical lesions

Immunochemical analysis of HPV L1 capsid protein and p16 protein in liquid-based cytology samples from uterine cervical lesions

Comparison of Predictors for High-Grade Cervical Intraepithelial Neoplasia in Women with Abnormal Smears

P634A4 and TAp73 immunocytochemistry in liquid-based cervical cytology—potential biomarkers for diagnosis and progress prediction of cervical neoplasia

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