>> P-428: P16INK4a and ProExC in HPV-associated squamous intraepithelial lesions of the cervix
19:00 PM - 19:00 PM
1Department of Pathology, Sherbrooke University, Sherbrooke, QC, Canada; 2Department of Pathology, St Pantelimon Hospital, Bucharest, Romania; 3Department of Gynaecology, Sherbrooke University, Sherbrooke, QC, Canada.
Background: High-risk human papillomavirus (HR-HPV) infection is significantly associated with development of low-grade (LGSIL) and high-grade (HGSIL) squamous intraepithelial cervical lesions. Histological assessment of these lesions has significant interobserver variability and novel markers could improve the diagnosis. We used P16INK4a and ProExC immunostain and compared their expression with HPV genotype.
Methods: 36 HGSIL smears and the correspondent histological specimens were analysed with 10 control samples from hysterectomy without SIL history (61 samples). P16 and ProExC immunostain were performed and the slides, with correspondent HE stain, were evaluated by two pathologists. A standard interpretation (pattern and distribution) was used. PCR analysis for HR-HPV detection was performed on 49 blocs. Statistical analysis was conducted to determine interobserver agreement and markers performance.
Results: HR-HPV genotype was detected in 22/49 cases (45% type 16) with a statistically significant association between positive cases and HGSIL (p<0.0001).
In distinguishing noSIL from SIL, the level of sensibility and specificity for P16 and ProExC were equivalent (72% and 76% sensibility; 72% and 77% specificity). The positive predictive values (PPV) were 86.1 and 89.1 and the negative predictive values (NPV) were 52.0 and 58.3 for P16 and ProExC respectively.
In distinguishing noSIL and LGSIL from HGSIL, P16 was more sensitive than ProExC (84% vs 80%) but less specific (77% vs 82%). PPV were 73.3 and 77.7 and NPV were 87.1 and 85.2 for P16 and ProExC respectively.
The interobserver agreement, reflected by kappa coefficient, was 0.83 for HE stain, 0.91 for P16 and 0.95 for ProExC (p<0.0001).
Conclusions: P16INK4a and ProExC immunostaining correlates with the severity of SIL and improves interobserver concordance of diagnosis. We need a standard interpretation of immunostain to assure the reproducibility. P16INK4a and ProExC have an equivalent level of sensibility and specificity to distinguish noSIL from SIL but ProExC appears to provide a higher specificity for HGSIL.