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Interpretation of p16 INK4a /Ki‐67 dual immunostaining for the triage of human papillomavirus‐positive women by experts and nonexperts in cervical cytology
Author(s) -
Allia Elena,
Ronco Guglielmo,
Coccia Anna,
Luparia Patrizia,
Macrì Luigia,
Fiorito Corinna,
Maletta Francesca,
Deambrogio Cristina,
Tunesi Sara,
De Marco Laura,
GillioTos Anna,
Sapino Anna,
Ghiringhello Bruno
Publication year - 2015
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.21511
Subject(s) - colposcopy , medicine , cytology , cervical intraepithelial neoplasia , kappa , triage , gynecology , cervical cancer , confidence interval , obstetrics , immunostaining , pathology , cancer , immunohistochemistry , linguistics , philosophy , emergency medicine
BACKGROUND The triage of human papillomavirus (HPV)‐positive women is needed to avoid overreferral to colposcopy. p16 INK4a immunostaining is an efficient triage method. p16 INK4a /Ki‐67 dual staining was introduced mainly to increase reproducibility and specificity compared with stand‐alone p16 INK4a staining. METHODS Within a pilot project, HPV‐positive women were referred to colposcopy if cytology was abnormal or unsatisfactory or HPV testing was still positive after 1 year. For 500 consecutive women, a slide obtained during colposcopy was immunostained for p16 INK4a /Ki‐67 and independently interpreted by 7 readers without previous experience with dual staining. Four of these readers were experts in cervical pathology and 3 were not. Kappa values for multiple raters, sensitivity, and specificity for cervical intraepithelial neoplasia type 2‐positive histology were computed. Because women with normal cytology were underrepresented, estimates for all HPV‐positive women were obtained as weighted means of cytology‐specific estimates. RESULTS The overall kappa for HPV‐positive women was 0.70 (95% confidence interval [95% CI], 0.60‐0.77). Kappa values were not found to be significantly different between expert and nonexpert readers with regard to cervical cytology but were significantly increased ( P =. 0066) after consensus discussion. The overall specificity estimate for HPV‐positive women was 64.0% (95% CI, 57.4%‐70.2%): 66.7% (95% CI, 59.8%‐73.0%) for experts and 60.5% (95% CI, 59.8%‐73.0%) for nonexperts. Among women with abnormal cytology, the sensitivity was 85.5% (95% CI, 77.9%‐90.8%): 85.8% (95% CI, 77.9%‐91.2%) for experts and 85.1% (95% CI, 76.6%‐90.9%) for nonexperts. CONCLUSIONS p16 INK4a /Ki‐67 immunostaining demonstrated good reproducibility and specificity when triaging HPV‐positive women. Dual‐staining interpretation can be performed, after short training, even by staff who are not experts in cervical cytology. This allows HPV‐based screening with triage to be performed in settings in which such expert staff is not available. Cancer (Cancer Cytopathol) 2015;123:212–218. © 2014 American Cancer Society .