The Evaluation of p16ink4a Immunoexpression/Immunostaining and Human Papillomavirus DNA Test in Cervical Liquid-Based Cytological Samples

Nasioutziki, Maria; Daniilidis, Angelos; Dinas, Kostos; Kyrgiou, Maria; Valasoulis, George; Loufopoulos, P. D.; Paraskevaidis, E.; Loufopoulos, Aristotelis; Karakitsos, Petros

doi:10.1097/igc.0b013e3182009eea

Cited by 30 publications

(19 citation statements)

References 28 publications

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“…Twelve studies 23–25;28–33;36–38 used clone E6H4 as a primary antibody for p16 INK4a , other primary antibodies used were Clone 6H12 27 , Clone JC8 34 and 16P04 35 . Positivity criteria of p16 INK4a immunostaining differed between the studies.…”

Section: Resultsmentioning

confidence: 99%

“…Positivity criteria of p16 INK4a immunostaining differed between the studies. Five studies 25;30;33;37;38 made use of the nuclear scoring proposed by Wentzensen and Bergeron 39 . This scoring system takes into account nuclear staining and nuclear abnormalities (increased size, granular/hyperchromatic chromatin, irregular shape or variable morphology from cell to cell).…”

Section: Resultsmentioning

confidence: 99%

“…A total of 1740 women were enrolled. Eight studies performed a direct comparison with HC2 triage data 12;25;28;30–33;37 . The study of Denton et al 30 provided p16 INK4a immunocytochemistry data interpreted independently by 2 pathologists and 1 cytotechnologist.…”

Section: Resultsmentioning

confidence: 99%

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p16^INK4a immunocytochemistry versus human papillomavirus testing for triage of women with minor cytologic abnormalities

Roelens

Reuschenbach

Doeberitz

et al. 2012

Cancer Cytopathology

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Background The best method to identify women with minor cervical lesions that require diagnostic work-up remains unclear. We performed a meta-analysis to assess the accuracy of p16INK4a immunocytochemistry compared to hrHPV DNA testing with hybrid capture II (HC2) to detect cervical intraepithelial neoplasia (CIN2+ and CIN3+) in women with a cervical cytology showing atypical squamous cells of undetermined significance (ASC-US) or low-grade cervical lesions (LSIL). Methods A literature search was performed in three electronic databases to identify studies eligible for this meta-analysis. Results Seventeen studies were included in the meta-analysis. The pooled sensitivity of p16INK4a to detect CIN2+ was 83.2% (95%CI: 76.8–88.2%) and 83.8% (95%CI: 73.5–90.6%) in ASC-US and LSIL cervical cytology respectively; pooled specificities were 71.0% (95%CI: 65.0–76.4%) and 65.7% (95%CI: 54.2–75.6%). Eight studies provided both HC2 and p16INK4a triage data. p16INK4a and HC2 have a similar sensitivity and p16INK4a has significantly higher specificity in the triage of women with ASC-US (relative sensitivity: 0.95 (95%CI: 0.89–1.01); relative specificity: 1.82 (95%CI: 1.57–2.12)). In the triage of LSIL, p16INK4a has a significantly lower sensitivity but higher specificity compared to HC2 (relative sensitivity: 0.87 (95%CI: 0.81–0.94); relative specificity: 2.74 (1.99–3.76)). Conclusion The published literature indicates an improved accuracy of p16INK4a compared to HC2 testing in the triage of ASC-US. In LSIL triage p16INK4a is more specific but less sensitive.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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p16^INK4a immunocytochemistry versus human papillomavirus testing for triage of women with minor cytologic abnormalities

Roelens

Reuschenbach

Doeberitz

et al. 2012

Cancer Cytopathology

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“…A sensitivity ranging from 75%[26] to 95%[14] and specificity ranging from 23.3%[14] to 92%[27] has been previously reported. Moreover, p16 showed 46.2% positivity for LSIL lesions and 100% positivity for HSIL lesions.…”

Section: Discussionmentioning

confidence: 99%

p16 immunostaining as a predictor of anal and cervical dysplasia in women attending a sexually transmitted infection clinic

Pandhi

Bisherwal

Singal

et al. 2016

Indian J Sex Transm Dis

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Background:Carcinogenesis caused by human papillomavirus (HPV) leads to over-expression of p16 protein. p16 may act as a marker of HPV integration with host genome and serve as a surrogate marker of HPV oncogenesis.Materials and Methods:A single center study of 75 women (35 HIV-positive and 40 HIV-negative women) was conducted. Anal and cervical specimens were obtained for cytology and p16 immunostaining.Results:The sensitivity of p16 to diagnose anal and cervical dysplasia was 50% and 58.8%, respectively, whereas specificity was 98.6% and 100%, respectively. Positive predictive value for anal and cervical was 75% and 100%, whereas negative predictive value was 95.8% and 89.2%, respectively. A strong relationship between the grade of dysplasia and intensity of p16 immunoscore was observed (Pearson correlation r = 0.666, P < 0.0001 and r = 0.496, P < 0.0001 for anal and cervical, respectively).Conclusion:p16 immunostaining with greater specificity for high-grade lesions may improve the diagnostic accuracy, especially for high-grade lesions which have a high risk of progression to malignancy and thereby necessitate treatment.

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“…Another study [9] demonstrated that p16 INK4A ICC can significantly improve SP and PPV of colposcopy in the management of women with ASC-US cytology. Although studies vary in their methodological approach, and conclusions are usually drawn from cases pre-selected for colposcopy, they clearly demonstrate (1) a strong correlation between positive p16 INK4A cytological staining and the severity of the histological lesion [10,11,12]; (2) the potential to increase the accuracy of cytological examination [12,13,14,15,16,17], and (3) the potential for efficient triage of ASC-US [9,18,19,20], ASC-H [6,21], and LSIL [18,19,20] cases.…”

Section: What Are the Main Goals For Immunomarkers?mentioning

confidence: 99%

Immunomarkers in Gynecologic Cytology: The Search for the Ideal ‘Biomolecular Papanicolaou Test’

Pinto¹,

Degen

Villa

et al. 2012

Acta Cytologica

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Harnessing the knowledge we have gained on the cell cycle disruption caused by human papillomaviruses (HPV) will likely lead to improved screening modalities for cervical cancer and its precursors. An easily applied biomarker that has high specificity and sensitivity would represent an attractive alternative or complement to cytology and HPV testing. To date, a number of promising markers have been investigated. These include p16^INK4A, MIB-1, BD-ProEx C, and L1. Newer possibilities involve a variety of gene products associated with aberrations of chromosome 3q, such as telomerase, p63, and PIK3CA, as well the combination of biomarkers such as p16^INK4A and MIB-1 in the same assay. Although none of them has yet been incorporated into screening algorithms or found its way into routine practice, their performance characteristics remain a focus of current investigations. This review summarizes what we know and where we hope to go in translating basic pathobiology into clinical practice.

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The Evaluation of p16ink4a Immunoexpression/Immunostaining and Human Papillomavirus DNA Test in Cervical Liquid-Based Cytological Samples

Abstract: The findings suggest that p16INK4a immunostaining can improve the accuracy of cytological examination and HPV DNA test and may be particularly useful in the triage of low-grade lesions.

Cited by 30 publications

References 28 publications

p16^INK4a immunocytochemistry versus human papillomavirus testing for triage of women with minor cytologic abnormalities

p16^INK4a immunocytochemistry versus human papillomavirus testing for triage of women with minor cytologic abnormalities

p16 immunostaining as a predictor of anal and cervical dysplasia in women attending a sexually transmitted infection clinic

Immunomarkers in Gynecologic Cytology: The Search for the Ideal ‘Biomolecular Papanicolaou Test’

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The Evaluation of p16ink4a Immunoexpression/Immunostaining and Human Papillomavirus DNA Test in Cervical Liquid-Based Cytological Samples

Abstract: The findings suggest that p16INK4a immunostaining can improve the accuracy of cytological examination and HPV DNA test and may be particularly useful in the triage of low-grade lesions.

Cited by 30 publications

References 28 publications

p16INK4a immunocytochemistry versus human papillomavirus testing for triage of women with minor cytologic abnormalities

p16INK4a immunocytochemistry versus human papillomavirus testing for triage of women with minor cytologic abnormalities

p16 immunostaining as a predictor of anal and cervical dysplasia in women attending a sexually transmitted infection clinic

Immunomarkers in Gynecologic Cytology: The Search for the Ideal ‘Biomolecular Papanicolaou Test’

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Resources

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p16^INK4a immunocytochemistry versus human papillomavirus testing for triage of women with minor cytologic abnormalities

p16^INK4a immunocytochemistry versus human papillomavirus testing for triage of women with minor cytologic abnormalities