The triage of low-grade cytological abnormalities by the immunocytological expression of cyclin- dependent kinase inhibitor p16 versus Human Papillomavirus test: a real possibility to predict cervical intraepithelial neoplasia CIN2 or CIN2+

Objective: Assessing the hypothesis that p16INK4a immunocytochemistry (ICC) has better relevance than Human Papillomavirus (HPV) testing at detecting high-grade cervical intraepithelial neoplasia (HGCIN) upon histopathological diagnosis in women with abnormal cytologies such atypical squamous cells of undetermined significance (ASC-US) or low-grade squamous intraepithelial lesions (LSIL). Materials and Methods: A retrospective study of 63 selected cases (22 with ASC-US and 41 with LSIL) was performed at “St. Pantelimon” Clinical Hospital, Bucharest, Romania, using p16INK4a ICC and Linear Array HPV Genotyping Test. All cases have been followed-up by colposcopy and biopsies. The sensitivity and specificity of p16INK4a and HPV were analyzed by chi-squared test. Results: LSIL cytologies were more likely to be p16INK4a positive than those with ASC-US: OR=3.1, 95% CI (1.06–9.11). The processed data show that in women with LSIL the sensitivity of p16INK4a is 37.5% higher than that of high-risk(hr)-HPV (p=0.0050), whereas in ASC-US it is 44.5% higher (p=0.0577). In ASC-US, p16INK4a has a higher specificity (84.62%) than hr-HPV (53.85%); for LSIL cytologies, this difference is less steep: 58.82% for p16INK4a as compared to 47.06% for HPV. Conclusions: The p16INK4a is significantly more sensitive than hr-HPV in both low-grade abnormal cytologies and has higher specificity than HPV testing to detect HGCIN, mainly in women with ASC-US cytologies. Only women with ASC-US and LSIL cytologies who test positive for p16INK4a should be directed to colposcopy and/or biopsy. p16INK4a is a suitable immunocytochemical marker which increases the accuracy of diagnosis at women with low-grade cytologic abnormality.