Are adjunctive markers useful in routine cervical cancer screening? Application of p16<sup>INK4a</sup> and HPV‐PCR on ThinPrep samples with histological follow‐up

Schledermann, Doris; Andersen, Birthe; Bisgaard, Kirsten; Dohse, Marius; Ejersbo, Dorthe; Hoelund, B.; Horal, Peter; Lindh, Magnus; Ryd, Walter

doi:10.1002/dc.20822

Cited by 18 publications

(18 citation statements)

References 48 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%

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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%

“…However, there was a difference in the localization of the immunostaining. Two studies 27;36 only considered nuclear staining as a positive p16 INK4a staining reaction while 8 studies 23;24;28;29;31;32;34;35 considered both nuclear and/or cytoplasmic staining as a positive reaction.…”

Section: Resultsmentioning

confidence: 99%

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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“…In cervical cytology, various research studies have been performed to evaluate the potential usefulness of applying p16 immunocytochemical staining protocols, especially for the triage of equivocal or mildly abnormal Pap cytologic results. In most studies, a sensitivity similar to that of HPV testing, but at a substantially higher specificity rate, has been reported for p16 cytology when used for the triage of Pap cytologic results categorized as ASC-US or LSIL or containing atypical glandular cells [9][10][11][12][13][14] (reviewed by Cuschieri and Wentzensen 6 and Tsoumpou et al 8 ). Although this indicates the potential of p16 cytologic testing for the triage of abnormal Pap cytologic results, many of the research studies show limitations owing to the use of nonvalidated and nonstandardized immunocytochemical reagents and protocols, the lack of standardized interpretation protocols, and a low number of biopsy follow-up results available.…”

Section: Introductionmentioning

confidence: 99%

The Sensitivity and Specificity of p16INK4a Cytology vs HPV Testing for Detecting High-Grade Cervical Disease in the Triage of ASC-US and LSIL Pap Cytology Results

Denton

Bergeron²,

Klement³

et al. 2010

American Journal of Clinical Pathology

121

104

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We analyzed the performance of p16(INK4a) immunocytochemistry on a series of 810 retrospectively collected atypical squamous cells of undetermined significance (ASC-US) and low-grade squamous intraepithelial lesion (LSIL) cases with available biopsy follow-up data, including 94 cases of cervical intraepithelial neoplasia (CIN) 2 and 128 cases of CIN 3. Human papillomavirus (HPV) testing was performed from the same residual liquid-based cytologic specimen, and results for both tests were correlated with histologic follow-up data. Sensitivity values for high-grade CIN (HGCIN) confirmed on biopsy within 6 months were 92.6% (ASC-US) and 92.2% (LSIL) for cytotechnologists' reviews of p16 cytology and 90.1% (ASC-US) and 95.7% (LSIL) for HPV testing. Sensitivity rates of initial pathologists' reviews were slightly lower, 76.4% to 80.1%, with levels comparable to cytotechnologists' results after adjudication. The specificity of p16 cytology for HGCIN detection was significantly higher than for HPV testing for cytotechnologists and pathologists: 63.2% to 71.1% (p16 cytology) vs 37.8% for HPV in ASC-US (P < .001) and 37.3% to 53.3% (p16 cytology) vs 18.5% for HPV in LSIL (P < .001). This evaluation of the diagnostic performance of p16 cytology confirms the potential of this stain for the efficient triage of ASC-US and LSIL cytologic results.

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“…[1][2][3][4][5][6][7][8] In the majority of the studies, p16 cytology was found to provide sensitivity rates for the detection of underlying high-grade cervical intraepithelial neoplasia (CIN of grade 2 or higher, CIN2þ), which were similar or slightly lower compared with the sensitivity of testing for the presence of human papillomavirus (HPV) infections. 7,9,10,11 At the same time, specificity of p16 cytology-based testing was found to be substantially higher than the specificity of HPV testing in all studies.…”

mentioning

confidence: 99%

p16/ki‐67 dual‐stain cytology in the triage of ASCUS and LSIL Papanicolaou cytology

Schmidt¹,

Bergeron²,

Denton³

et al. 2011

Cancer Cytopathology

207

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BACKGROUND:The objective of this study was to analyze the diagnostic performance of a newly established immunocytochemical dual‐stain protocol, which simultaneously detects p16INK4a and Ki‐67 expression in cervical cytology samples, for identifying high‐grade cervical intraepithelial neoplasia (CIN2+) in women with Papanicolaou (Pap) cytology results categorized as atypical squamous cells of undetermined significance (ASCUS) or low‐grade squamous intraepithelial lesions (LSIL).METHODS:Residual liquid‐based cytology material from 776 retrospectively collected ASCUS/LSIL cases that were available from a recent study evaluating p16 cytology and HPV testing were subjected to p16/Ki‐67 dual staining. The presence of 1 or more double‐immunoreactive cell(s) was regarded as a positive test outcome, irrespective of morphology. Test results were correlated to histology follow‐up.RESULTS:Sensitivity of p16/Ki‐67 dual‐stain cytology for biopsy‐confirmed CIN2+ was 92.2% (ASCUS) and 94.2% (LSIL), while specificity rates were 80.6% (ASCUS) and 68.0% (LSIL), respectively. Similar sensitivity/specificity profiles were found for both age groups of women aged <30 years versus women aged ≥30 years. Dual‐stain cytology showed comparable sensitivity, but significantly higher specificity, when compared with human papillomavirus (HPV) testing.CONCLUSIONS:The results of this study show that p16/Ki‐67 dual‐stain cytology provided a high sensitivity for the detection of underlying CIN2+ in women with ASCUS or LSIL Pap cytology results, comparable to the rates previously reported for HPV testing and p16 single‐stain cytology. However, the specificity of this morphology‐independent interpretation of p16/Ki‐67 dual‐stain cytology testing was further improved compared with the earlier p16 single‐stain cytology approach, which required morphology interpretation, and it is significantly higher when compared with HPV testing. Cancer (Cancer Cytopathol) 2011;. © 2011 American Cancer Society.

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Are adjunctive markers useful in routine cervical cancer screening? Application of p16^INK4a and HPV‐PCR on ThinPrep samples with histological follow‐up

Cited by 18 publications

References 48 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

The Sensitivity and Specificity of p16INK4a Cytology vs HPV Testing for Detecting High-Grade Cervical Disease in the Triage of ASC-US and LSIL Pap Cytology Results

p16/ki‐67 dual‐stain cytology in the triage of ASCUS and LSIL Papanicolaou cytology

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Are adjunctive markers useful in routine cervical cancer screening? Application of p16INK4a and HPV‐PCR on ThinPrep samples with histological follow‐up

Cited by 18 publications

References 48 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

The Sensitivity and Specificity of p16INK4a Cytology vs HPV Testing for Detecting High-Grade Cervical Disease in the Triage of ASC-US and LSIL Pap Cytology Results

p16/ki‐67 dual‐stain cytology in the triage of ASCUS and LSIL Papanicolaou cytology

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Product

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Are adjunctive markers useful in routine cervical cancer screening? Application of p16^INK4a and HPV‐PCR on ThinPrep samples with histological follow‐up

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