Background: Hybrid Capture2 (HC2) test provides semi-quantitative estimation of viral load of 13 high-risk Human Papilloma Virus (HPV) in cervical specimens. Viral load measurement may help to identify higher grades of cervical neoplasias more efficiently. A higher threshold of viral load may help in identifying the group at highest risk for development of high grade CIN.
Aim: Purpose of the study was to evaluate HPV viral load determined by HC2 as potential bio-marker for detection of CIN3+ disease.
In this population-based study cervical samples for HC2 were collected from 37,050 women aged 30-60 years. HC-2 test output was shown as relative light units/positive controls (RLU/PC), which was a surrogate for HPV viral load. RLU/PC value of 1.0 (equivalent to 1pg/ml viral load) was considered positive. All HC2 positive women had Colposcopy and cervical biopsy. Strength of association of viral load of HC2 +ve women with histologically diagnosed CIN3+ was measured. For this purpose RLU/PC values of positive women were grouped into three categories:1-<10; 10-<100 and ≥100.
Median viral load for HC2+ve CIN1, CIN2, CIN3 and invasive cancers were 40.5, 195.2, 682.0 and 705.8 respectively. Multiple logistic regression after adjusting confounding factors like age, parity and menopausal status showed odds ratio for CIN3+ disease to be 6.1 (95%C.I. 2.6-14.5) for RLU/PC of 1-<10; 18.0 (95%C.I. 8.2-39.6) for RLU/PC of 10-<100 and 41.0 (95%C.I. 20.8-81.1) for RLU/PC ≥100. ROC curve analysis to detect CIN3+ at various RLU/PC cut-offs showed optimal combination of sensitivity and specificity (92.3% and 81.4% respectively) at RLU/PC cut-off value of 1.1. However, in women above 49 years, higher cut-off of 14.9 gave optimal combination of sensitivity and specificity (97.7% and 85.8% respectively) to detect CIN3+.
Higher viral load on HC2 is associated with increasing grades of cervical neoplasias. Women with increased viral load need close follow-up