Viral Load in the Natural History of Human Papillomavirus Type 16 Infection: A Nested Case–Control Study

Background. Viral load may influence the course of human papillomavirus type 16 (HPV-16) infection. Methods. This case-control study was nested within the 2-year Atypical Squamous Cells of Undetermined Significance and Low-Grade Squamous Intraepithelial Lesion Triage Study, in which women were followed semiannually for HPV and cervical intraepithelial neoplasia (CIN). Case patients (n 5 62) were women diagnosed with CIN3 following HPV-16–positive detection at a follow-up visit. HPV-16–positive controls (n 5 152) without CIN2 or CIN3 were matched to cases based on the follow-up visit in which viral load was measured. Real-time polymerase chain reaction was used for HPV-16 DNA quantification. Results. The risk of CIN3 increased with increasing HPV-16 DNA load at the follow-up visit (odds ratio, 1.63; 95 % confidence interval, 1.33–1.99 per 1 log10 unit increase); the association was not affected by whether HPV-16 was present at enrollment. When HPV-16 was present at both enrollment and follow-up, viral load remained high among cases (P 5.77) but decreased substantially among controls (P 5.004). Among women with HPV-16 found initially during follow-up, viral load in the first HPV-16–positive sample was associated with short-term persistence; load was higher in those with infection, compared with those without infection, 1 visit after the initial positivity (P 5.001). Conclusions. Viral load of newly detected infections and changes in viral load predict persistence an