Viral load in the natural history of human papillomavirus type 16 infection: a nested case-control study

Abstract

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 = 62) were women diagnosed with CIN3 following HPV-16-positive detection at a follow-up visit. HPV-16-positive controls (n = 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 log(10) 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 = .77) but decreased substantially among controls (P = .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 = .001).

Conclusions: Viral load of newly detected infections and changes in viral load predict persistence and progression of HPV-16 infections.

Figure 1.

Mean (square) and 95% confidence interval (upper and lower bound) of log₁₀ human papillomavirus type 16 E7 copies per 1 nanogram (ng) of cellular DNA detected in the first positive sample, stratified by the time to diagnosis of cervical intraepithelial neoplasia 3 (CIN3) from the newly detected infection.

Figure 2.

Mean (square) and 95% confidence interval (upper and lower bound) of log₁₀ human papillomavirus type 16 E7 copies per 1 nanogram (ng) of cellular DNA detected in enrollment (solid line) and follow-up (dashed line) samples among case patients (Figure 1A) and control subjects (Figure 1B), stratified by the follow-up visits from which samples were assayed for viral load.