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Meta‐analysis of the accuracy of p16 or p16/Ki‐67 immunocytochemistry versus HPV testing for the detection of CIN2+/CIN3+ in triage of women with minor abnormal cytology
Author(s) -
Peeters Eliana,
Wentzensen Nicolas,
Bergeron Christine,
Arbyn Marc
Publication year - 2019
Publication title -
cancer cytopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.29
H-Index - 57
eISSN - 1934-6638
pISSN - 1934-662X
DOI - 10.1002/cncy.22103
Subject(s) - medicine , squamous intraepithelial lesion , cervical intraepithelial neoplasia , confidence interval , triage , cytology , colposcopy , papanicolaou test , cervical cancer , gynecology , cancer , pathology , papanicolaou stain , emergency medicine
Background Women with atypical squamous cells of undetermined significance (ASC‐US) can be triaged accurately with a high‐risk human papillomavirus (hrHPV) test to identify those who need a referral. However, the triage of low‐grade squamous intraepithelial lesion (LSIL) with hrHPV testing has very low specificity. Overexpression of p16, with or without Ki‐67, indicates neoplastic transformation of human papillomavirus–infected cervical cells and may more accurately predict underlying cervical intraepithelial neoplasia of grade 3 or worse (CIN3+). Methods A literature search was conducted in 3 bibliographic databases. Studies were selected if they included women with ASC‐US or LSIL who were triaged with dual staining (p16/Ki‐67) and/or p16 staining and, if available, with a comparator hrHPV test to detect cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) or CIN3+. Results Thirty‐eight studies were eligible. The sensitivity of p16 staining for CIN3+ was significantly lower than that of hrHPV DNA testing (ratio for ASC‐US, 0.87; 95% confidence interval [CI], 0.78‐0.97; ratio for LSIL, 0.86; 95% CI, 0.80‐0.93). In contrast, the specificity of p16 staining was substantially higher with relative specificities of 1.60 (95% CI, 1.35‐1.88) and 2.29 (95% CI, 2.05‐2.56) for ASC‐US and LSIL respectively. Dual staining was as sensitive as hrHPV DNA testing but was more specific (ratio for ASC‐US, 1.65; 95% CI, 1.42‐1.92; ratio for LSIL, 2.45; 95% CI, 2.17‐2.77). Conclusions This meta‐analysis confirms that p16 staining and p16/Ki‐67 staining are more specific for CIN2+/CIN3+ than hrHPV DNA testing. Although p16 staining is less sensitive for CIN3+ than hrHPV DNA testing, dual staining has similar sensitivity.