p16INK4α/Ki-67 immunocytochemical dual staining for detection of cervical lesions associated to papillomavirus infection.

We aimed to explore the expression pattern of p16(INK4 alpha)/Ki-67 immunocytochemical dual-staining and to establish the potential clinical utility for early detection of cervical lesions. Liquid-based cytologies of cervical specimens of cervical cancer screening were processed for p16(INK4 alpha)/Ki-67 immunocytochemical dual-staining using the CINtec (R) Plus Kit. HPV testing was performed with the INNO-LiPA HPV genotyping Extra Reverse Hybridization Line Probe Assay kit. One hundred and fifteen cervical cytologies were analyzed with the following results: 11(9.6%) were negative for intraepithelial lesions or malignancy (NILM); 32(27.8%) presented atypical squamous cells of undetermined significance (ASC-US); 62(53.9%) exhibited low grade squamous intraepithelial lesions (LSIL) and 10(8.7%) showed high grade squamous intraepithelial lesions (HSIL). No cases of cervical cancer were detected. The overall prevalence of DNA HPV detection was 81.7% (94/115). The following specific HPV genotypes were identified in 42 (45.0%) cases: HPV16 (26.2%), HPV51 (21.4%), HPV52 (14.3%) and HPV66 (7.1%). Viral sequences of an unknown single HPV were detected in 23.8% of the cases. A total of 42/115 (36.5%) were p16/1K4a/Ki-67 dual-staining-positive, being more frequent in HSIL (70.0%), decreasing in LSIL (44.0%), detected in a minority of ASC-US (25.0%) and negative in NILM cases (p<0.001). 40/115 cases (34.8%) were positive for both oncogenic HPV and p16(INK4 alpha)/Ki-67 dual-staining, including 6/32 (18.8%) ASC-US, 26/62 (42.0%) LSIL and 8/10 (80.0%) HSIL, which represent a strong association between positivity for HPV, p16"vma/Ki-67 staining and severe cytological abnormalities Q.<0.001). This methodology could be used to detect unnoticed cervical lesions.