Comparison of Cytology, Colposcopy, HPV Typing and Biomarker Analysis in Cervical Neoplasia

Background: Cervical cancer is the leading cause of mortality among women worldwide, despite existing prevention programs. In light of the recent development of anti-HPV vaccines, the aim of this study was to evaluate concurrently the efficacy of four methods for risk assessment (cytology, colposcopy, HPV molecular typing and detection of biomarkers in cervical biopsies) in an attempt to define the most efficient combination. Patients and Methods: The studied group included 62 women with abnormal Pap tests and cervical lesions ranging from cervicitis and condylomas to intraepithelial neoplasias and invasive cancer. All women underwent full colposcopy assessment and colposcopically-taken biopsies were selected for histological examination, immunohistochemical identification of p16, p53, Bcl-2 biomarkers, as well as molecular detection and typing of HPV genomes. Results: Cytology and colposcopy showed very high sensitivity in detecting CIN and cancer (91.7% and 94.4%, respectively), but low specificity (34.6% and 50%, respectively). The detection of the 3 biomarkers reached an impressive sensitivity (83.3%) and a moderate specificity (65.4%). HPV detection and typing achieved 77.8% sensitivity, and the highest specificity. of 80.8% in detecting CIN and cancer cases. HPV DNA testing had the highest positive prognostic value (84.9%; confidence interval, CI: 67.4%-94.3%) and cytology the lowest (66.0%; CI: 51.2%-78.4%). Coupled HPV typing and colposcopy proved to be the most efficient combination, increasing sensitivity to 97.2% and negative prognostic value to 92.3%. The estimation of cervical neoplasia or cancer in women with high-risk HPV types increased approximately 15-fold (odds ratio, OR: 14.70; CI: 4.30-50.09, p<0.001), similar to 23-fold in the case of combined positive biomarkers (OR: 23.18; CI: 4.97-104.23, p<0.001), and 35-fold in case of colposcopically detected cervical neoplasia (OR: 35.00; CI: 5.16-225.07, p<0.001). Conclusion: The most efficient combination among all tested methodologies was found to be HPV typing with colposcopy.