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KMID : 1137020180290030038
Journal of Gynecologic Oncology
2018 Volume.29 No. 3 p.38 ~ p.38
E2/E6 ratio and L1 immunoreactivity as biomarkers to determine HPV16-positive high-grade squamous intraepithelial lesions (CIN2 and 3) and cervical squamous cell carcinoma
Choi Youn-Jin

Lee Ah-Won
Kim Tae-Jung
Jin Hyun-Tak
Park Jong-Sup
Lee Sung-Jong
Abstract
Objective: Human papillomavirus (HPV) 16 is the most carcinogenic HPV genotype. We investigated if HPV16 L1 capsid protein and E2/E6 ratio, evaluated by cervical cytology, may be used as biomarkers of ¡Ãcervical intraepithelial neoplasia (CIN) 2 lesions.

Methods: Cervical specimens were obtained from 226 patients with HPV16 single infection. Using cytology specimen, L1 capsid protein and E2/E6 ratio were detected and the results were compared with those of the conventional histologic analysis of cervical tissues (CIN1?3 and squamous cell carcinoma [SCC]) to evaluate the association.

Results: The L1 positivity of CIN2/3 was significantly lower than that of normal cervical tissue (p<0.001) and SCC demonstrated significantly lower L1 positivity than CIN1 (p<0.001). The mean E2/E6 ratios of specimens graded as SCC (0.356) and CIN2/3 (0.483) were significantly lower than those of specimens graded as CIN1 (0.786) and normal (0.793) (p<0.05). We observed that area under the receiver operating characteristic curve (AUC) for E2/E6 ratio (0.844; 95% confidence interval [CI]=0.793?0.895) was higher than that for L1 immunochemistry (0.636; 95% CI=0.562?0.711). A combination of E2/E6 ratio and L1 immunocytochemistry analyses showed the highest AUC (0.871; 95% CI=0.826?0.917) for the prediction of ¡ÃCIN2 lesions.

Conclusion: To our knowledge, this is the first study to validate HPV L1 capsid protein expression and decreased HPV E2/E6 ratio as valuable predictive markers of ¡ÃCIN2 cervical lesions. Cervical cytology may be analyzed longitudinally on an outpatient basis with noninvasive procedures as against invasive conventional histologic analysis.
KEYWORD
Cervical Intraepithelial Neoplasia, Uterine Cervical Neoplasms, Human Papillomavirus Type 16 L1 Protein, Immunocytochemistry, Viral Integration
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