The significance of Human Papillomavirus viral load by using hybrid capture II assay in diagnosis of CIN II or above in women with PAP smear showing only ASCUS/LSIL

Kwon, Min Jung; Song, Eun Jeong; Kim, Chang Woon; Hong, Seong Nam; Eum, Sang Tak

Abstract

OBJECTIVE
To determine the clinical significance of high risk Human papillomavirus (HPV) DNA viral load measured by hybrid capture (HC) II assay in diagnosis of CIN II or above in women with cervical smear showing only Atypical squamous cells of undetermined significance (ASCUS)/Low-grade squamous intraepithelial lesion (LSIL).
METHODS
This study was performed from September 2003 to September 2004 and included 111 patients with ASCUS/LSIL on PAP smear. All of them underwent high risk HPV DNA tests by HC II assay and colposcopy directed cervical biopsies. The histologic results were classified as low grade lesion (normal, CIN I) and high grade lesion (CIN II, III, and invasive cancer). The viral load was transformed into their logarithm (Log10RLU/PC ratio), and categorized as following four groups; negative HPV DNA (Log10RLU/PC< or =0), low viral load (0.01-0.99), middle viral load (1.00-1.99), high viral load (> or =2.0). We evaluated the relationships of the detection rate and viral load of high risk HPV DNA with histologic severity of cervical lesions.
RESULTS
The rate of CIN II or above in 111 patients with ASCUS/LSIL was 25.2%. The detection rate of high risk HPV DNA using HC II assay was 96.4% in high grade lesion, and 66.3% in low grade lesion of histologic test. There was strong correlation between CIN II or above and positivity for HPV DNA when this group was compared with women with only CIN I or normal cervix (OR:13.7, 95% CI:1.7-106.4). The higher the viral load of HPV DNA infection observed, the higher the probability of being associated with stage of CIN (correlation coefficient:0.279). The frequency of high viral load observed in high grade lesion (89.3%) was significantly higher than low grade lesion (33.7%)(OR:16.3, 95% CI:4.5-58.9). When the cutoff of positivity was changed from 1.0RLU/PC ratio to 100.0RLU/PC ratio (Log10 RLU/PC ratio=2.0), the sensitivity for the prediction of high grade lesion was slightly decreased (96.4->89.3%), but pronounced gain in specificity (33.7->66.3%), and reduction in false positive rate (66.3->33.7%).
CONCLUSION
The viral load of high risk HPV DNA measured by HC II assay was significantly associated with the severity of histology, and useful in diagnosis of CIN II or above in women referred because of ASCUS/LSIL on PAP smear.