Implications of semi-quantitative HPV viral load estimation by Hybrid capture 2 in colposcopy practice

Objective: High viral load of oncogenic human papillomavirus (HPV) significantly increases risk of CIN 2 or worse (CIN 2+) lesions. Semi-quantitative estimation of oncogenic HPV viral load by Hybrid Capture 2 (HC2) correlates well with viral load estimated by real-time polymerase chain reaction. We correlated viral load estimated by HC2 with colposcopy and histology diagnosis, to determine if high viral load could detect the CIN 2+ lesions missed by colposcopy in HPV positive women. Methods: Using HPV testing by HC2, 39,728 women were screened. Positive results were categorized into low-positive, intermediate, and high viral load groups, based on relative light unit/cut-off ratios. HPV-positive and some HPV-negative women underwent colposcopy and biopsy. Results: A total of 278 CIN 2+ lesions were detected. Detection rate of CIN 2+ was significantly higher in intermediate and high viral load groups. Nearly half (48.3%) of CIN 2+ and 80.4% of CIN 3+ lesions missed or under-diagnosed by colposcopy had viral load in intermediate to high ranges. Risk of CIN 2+ in the high viral load group was 46 times higher than HPV-negative women, even when colposcopy was apparently normal. Discussion: Women with intermediate or high viral load should have multiple punch biopsies, even if colposcopy is apparently normal or suggests low grade lesions. Women with high viral load and suspected low grade lesion on colposcopy may be considered for 'see-and-treat', as their risk of CIN 2+ is nearly 200 times higher than HPV-negative women.