Correlation Between p16/Ki-67 Expression and the Grade of Cervical Intraepithelial Neoplasias.

Interpretation of histopathology of cervical premalignant lesions suffers from marked interobserver variability due to its subjective nature. We aimed to evaluate the usefulness of the biomarkers p16 and Ki-67 in improving the diagnostic accuracy of cervical histopathology and assess the correlation between p16 expression and human papillomavirus test in different grades of cervical intraepithelial neoplasia (CIN). Cervical tissue specimens with a diagnosis of CIN 1 or worse (CIN 1+) on hematoxylin and eosin staining were selected for immunohistochemistry (IHC) staining for p16 and Ki-67. The IHC slides were examined by a gynecologic pathologist along with a review of hematoxylin and eosin slides. The review histopathology diagnosis was used to correlate with the IHC results. We observed that the proportion of women with overexpression of p16 increased with increasing histologic severity: 0% in women with normal histology; 33.3% in women with CIN 1; 58.1% in women with CIN 2; and 73.8% in women with CIN 3. Among the human papillomavirus-positive women, 76.3% (58/76) women with CIN 2/CIN 3 expressed p16, and only 8.9% (4/45) women with normal histopathology or CIN 1 expressed the same. A combination of p16 positivity and abnormal expression of Ki-67 beyond the lower third of the epithelium was observed in 0% of normal/CIN 1 and 60.5% (40/66) of CIN 3 detected on routine histopathology. We concluded that dual staining could be used as an adjunctive test to improve the diagnostic accuracy of histopathology. In addition, p16/Ki-67 IHC has a role in guiding management decisions in cases with discordant colposcopy and histopathology diagnoses.

The role of low-level magnification in visual inspection with acetic acid for the early detection of cervical neoplasia.

Several studies have investigated the accuracy of naked eye visual inspection with acetic acid (VIA) in the early detection of cervical neoplasia. It is not clear whether low-level (2-4x) magnification (VIAM) can improve the sensitivity and specificity of VIA. The accuracy of both VIA and VIAM, provided by independent health workers, were evaluated in three cross-sectional studies involving 18,675 women aged 25-65 years in Kolkata and Mumbai in India. All screened women were investigated with colposcopy and biopsies were obtained based on colposcopy findings. The final disease status was based on the reference standard of histology (if biopsies had been taken) or colposcopy. Data from the studies were pooled to calculate the test characteristics for the detection of high-grade squamous intraepithelial lesions (HSIL). 14.1% and 14.2% were positive on testing with VIA and VIAM respectively. Two hundred twenty-nine were diagnosed with HSIL and 68 with invasive cancer. The pooled sensitivity, specificity, positive and negative predictive values for VIA in detecting high-grade squamous intraepithelial lesions (HSIL) were 60.3% (95% CI: 53.6-66.7), 86.8% (95% CI: 86.3-87.3), 5.9% (95% CI: 5.0-7.0), and 99.4% (95% CI: 99.2-99.5), respectively. The values were 64.2% (95% CI: 57.6-70.4), 86.8% (95% CI: 86.2-87.3), 6.3% (95% CI: 5.3-7.3) and 99.4% (95% CI: 99.3-99.6), respectively, for VIAM. Low-level magnification did not improve the test performance of naked eye visualization of acetic acid impregnated uterine cervix.