Evidence map›Paper›PMID 27515495›Full record

ReviewModern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc2016

p16ink4 and cytokeratin 7 immunostaining in predicting HSIL outcome for low-grade squamous intraepithelial lesions: a case series, literature review and commentary.

Eric C Huang, Mary M Tomic, Suchanan Hanamornroongruang, Emily E Meserve, Michael Herfs, Christopher P Crum

Abstract readReview
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In one paragraph

Review in Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Article
  6. Cervical Carcinoma: Oncobiology and Biomarkers.International journal of molecular sciences · 2021
    Review
  7. Article
  8. Article
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  10. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Eric C HuangDepartment of Pathology and Laboratory Medicine, University of California, Davis Medical Center, Sacramento, CA, USA.
Mary M TomicDepartment of Pathology and Laboratory Medicine, University of California, Davis Medical Center, Sacramento, CA, USA.
Suchanan HanamornroongruangDepartment of Pathology, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Emily E MeserveDivision of Women's and Perinatal Pathology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Michael HerfsLaboratory of Experimental Pathology, GIGA-Cancer, University of Liege, Liege, Belgium.
Christopher P CrumDivision of Women's and Perinatal Pathology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Funding

The squamocolumnar junction and cervical cancerR21CA173190 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI CRUM, CHRISTOPHER PAUL, MCKEON, FRANK D. · 2013 to 2014
$451k
NCI NIH HHS R21 CA173190
6 · The paper itself

Abstract

p16ink4 and cytokeratin 7 (CK7) have been proposed to identify low-grade squamous intraepithelial lesions (LSIL) at greater or lesser risk for an outcome of high-grade squamous intraepithelial lesion (HSIL). We correlated CK7 and p16ink4 staining in LSILs with outcome on follow-up and placed this information in the context of prior reports. Cervical LSIL biopsies with at least 1-year follow-up information were immunostained for CK7 and p16ink4. Follow-up outcomes included no SIL, LSIL (persistence) or HSIL (CIN2+). In all, 109 LSILs were studied and 18.3% stained positive for CK7. Ninety-one percent of CK7-negative LSILs regressed, 4.5% persisted, and 4.5% had an HSIL outcome, versus 60, 20, and 20% of CK7-positive LSILs, respectively (P=0.036). p16ink4 status did not significantly associate with outcome. Review of the literature revealed a highly variable rate of both positive p16ink4 immunoreactivity in LSIL and CIN2+ outcome for p16-positive LSIL but a consistently high negative predictive value (>90%) in the case of no/low p16 expression. Inter-observer reproducibility for the diagnosis of CIN2 in the literature ranged from poor to good, with unanimous agreement on the diagnosis of CIN2 occurring in less than 25% of cases. As with high-risk human papillomavirus testing, the most clinically useful result of p16ink4 staining is a negative test, implying no lesion or CIN1 and conferring a low risk of HSIL outcome. HSIL outcomes ('progression') are highly variable and are subject to wide differences in inter-observer interpretation for CIN2. This argues against the wisdom of relying on p16ink4 to both predict CIN2+ or upgrade CIN1 to CIN2. It also begs the question of whether CIN2 should be replaced by an alternate and less pejorative term (SIL of intermediate grade) for lesions that are not reproducibly classified as LSIL or HSIL, with an appropriate management scheme.

Indexed as

Biomarkers, TumorCyclin-Dependent Kinase Inhibitor p16FemaleHumansKeratin-7Predictive Value of TestsPrognosisSquamous Intraepithelial Lesions of the CervixBiomarkers, TumorCyclin-Dependent Kinase Inhibitor p16Keratin-7

Identifiers

PMID27515495

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.