P16(INK4a) immunocytochemistry in liquid-based cytology samples in equivocal Pap smears: added value in management of women with equivocal Pap smear.
OBJECTIVE
To test whether p1l6(INK4a) immunocytochemistry (ICC) in liquid-based cytology (LBC) is useful with colposcopy in abnormal Pap smears.


METHODS
A series of 248 women with abnormal Pap smear were analyzed for oncogenic (HR) human papillomavirus (HPV) types using the Hybrid Capture II assay and for p16(INK4a) expression using ICC on cervical samples in PreservCyt liquid media. Colposcopic and loop electrosurgical excision procedure (LEEP) cone biopsy were the gold standard.


RESULTS
p16(INK4a) ICC did best as predictor of high-grade squamous intraepithelial lesion, with OR 12.18 (2.72-54.57) (p = 0.0001), showing 88.2% sensitivity (SE), 61.9% specificity (SP), 14.6% positive predictive value (PPV) and 98.6% negative predictive value (NPV). In sorting discrepant cases, p16(INK4a) ICC results in 100% SE and 100% NPV in detecting cervical intraepithelial neoplasia (CIN) 2 lesions among Pap+/biopsy- women. In atypical squamous cells undetermined significance (ASCUS) cytology, adding p16(INK4a) ICC improves specificity of colposcopy from 27.3% to 81.8% and PPV from 42.8% to 71.4%. Best performance is obtained with p16(INK4a) ICC and colposcopy: 83.3% SE, 81.8% SP, 71.4% PPV and 90.0% NPV. CONCLUSION p16(INK4a) is useful in sorting clinically relevant discrepant cases, and p16(INK4a) ICC significantly improves SP and PPV of colposcopy in management of ASCUS cytology.
Monsonego
Joseph
J
Alfred Fournier Institute, Paris, France. jm@eurogin.com
Pollini
Giuseppe
G
Evrard
Maria José
MJ
Sednaoui
Patrice
P
Monfort
Laura
L
Quinzat
Dominique
D
Dachez
Roger
R
Syrjänen
Kari
K
D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy; D002584:Cervix Uteri / Q000473:pathology; D003127:Colposcopy; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D065006:Papanicolaou Test; D011237:Predictive Value of Tests; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000473:pathology; D014626:Vaginal Smears; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis* / Q000473:pathology
D019941:Cyclin-Dependent Kinase Inhibitor p16