Abstract LB-135: Biomarker utility of the E2/E6 ratio and L1 immunoreactivity for determining HPV16-positive ≥CIN2 lesions and cervical squamous cell carcinoma

Abstract

Abstract Objectives: Human papillomavirus (HPV)16 is the most carcinogenic HPV genotype. The objective of this study was to identify whether expression of the HPV16 L1 capsid protein and the E2/E6 ratio—both determined by cervical cytology—could be used as biomarkers of cervical pre-malignancy and cancer. Methods: Cervical specimens were obtained from 226 patients with HPV16 single infection at Seoul St. Mary's Hospital. A Cytoactiv®HPV L1 screening set was prepared to detect the L1 capsid protein, and real-time polymerase chain reaction (PCR) was performed to determine the E2/E6 ratio of HPV16 DNA. Cytology results then were compared to results of conventional histologic analysis of cervical tissues (cervical intraepithelial neoplasia [CIN]1-3 and squamous cell carcinoma [SCC]) to evaluate the association. Results: We found that the mean E2/E6 ratios of specimens graded as SCC (0.355) and of those graded as CIN2/3 (0.481) were significantly lower than the mean E2/E6 ratios for specimens graded as CIN1 (0.736) and those regarded as normal (0.792) (P < 0.05). Cytologic detection of HPV L1 enabled prediction of ≥CIN2 cervical lesions and differentiation of CIN2/3 from SCC (P < 0.05). Based on findings expressed as area under the receiver operating characteristic curve (AUC), the combination of HPV L1 immunohistochemistry and the E2/E6 ratio predicted ≥CIN2 cervical lesions (AUC, 0.871; 95% confidence interval, 0.826-0.917) better than either individual test. Conclusions: To our knowledge, this study is the first to validate the expression of the HPV L1 capsid protein and a decreased HPV E2/E6 ratio as valuable predictive markers of ≥CIN2 cervical lesions, thereby discriminating cervical pre-malignancy and cancer. Cervical cytology can be analyzed on an outpatient basis with noninvasive procedures, in contrast to conventional histologic analysis, which is invasive. Moreover, cervical cytology can be conducted longitudinally to evaluate disease progression/regression without repeated invasive procedures. Citation Format: Youn Jin Choi, Sung-Jong Lee. Biomarker utility of the E2/E6 ratio and L1 immunoreactivity for determining HPV16-positive ≥CIN2 lesions and cervical squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-135.