Abstract:
Background: The aim of this study was to evaluate the immunocytochemical expression of human papillomavirus (HPV) L1 capsid protein in patients with atypical squamous cells of unknown significance (ASCUS), and low grade squamous intraepithelial lesions (LSIL) at high risk of HPV infection. We want to investigate the association of HPV L1 capsid protein expression and its clinical significance.
Materials and Methods: Between January 2013 and December 2017, we performed immunocytochemistry of HPV L1 protein in cervical cytology samples (49 normal cytology, 70 ASCUS, and 215 LSIL) obtained from 334 patients using the Cytoactiv® HPV L1 screening set. The expression of HPV L1 capsid protein was assessed by using cytology and was compared with the results of histopathological examination of surgical samples.
Results: Patients with ASCUS (n=70) or LSIL (n=215) in cervical cytology differently showed negativity for L1 capsid protein when they were diagnosed as ≥ cervical intraepithelial neoplasia (CIN) 2 (ASCUS group: 82.6%, P=00046; LSIL group: 72.2%, P=0.02). The negativity for L1 capsid protein was significantly higher in patients with HPV 16 or 18 infection when they were diagnosed as ≥CIN 2 (P=0.03). The risk of ≥CIN 2 was higher in ASCUS with HPV L1 capsid protein negative group than LSIL or negative group (Odds ratio: 14.7, 95% CI 3.5-64.5, P<0.001). Model comparison analysis revealed that cytology plus HPV capsid protein immunocytochemistry or cytology plus HPV test improved the diagnosis rate compared with cytology alone (AIC: 229.9 vs 236.0 vs 241.0; SC: 245.2 vs 251.3 vs 252.4). After adjustment of age and parity, HPV L1 capsid protein immunocytochemistry negativity (OR 4.16, 95% CI 1.86-9.33, P=0.0005) increased the risk of ≥CIN2 than HPV type 16or 18 infection (OR: 4.04, 95% CI 1.56-40.48, P=0.0042).
Conclusion: Our study demonstrates that the negativity of HPV L1 capsid protein in low-grade cytology (i.e., ASCUS and LSIL) is strongly associated with high-grade histopathology diagnoses. Especially, loss of L1 expression in ASCUS could be a potent prognostic marker for the development of CIN.
