Changes in DNA Level of Oncogenic Human Papillomaviruses Other Than Types 16 and 18 in Relation to Risk of Cervical Intraepithelial Neoplasia Grades 2 and 3.

Abstract

Epidemiologic data addressing clinical relevance of viral load fluctuation of oncogenic types other than human papillomavirus (HPV) types 16 and 18 are limited. A type-stratified set of infections by non-HPV16/18 oncogenic types that were detected at ≥2 visits was randomly selected from women who were enrolled in a clinical trial and followed every 6 months for 2 years for detection of HPV and cervical intraepithelial neoplasia grades 2 and 3 (CIN2/3). Type-specific viral load was measured on both first and last HPV-positive cervical swab samples. CIN2/3 was initially confirmed at the last HPV-positive visit for 67 of 439 infections. The increase in risk of CIN2/3 was associated with high, relative to low, viral load at both first and last positive visits [ORadjusted = 3.67; 95% confidence interval (CI), 1.19-11.32] and marginally associated with a change of viral load from low to high levels (ORadjusted = 3.15; 95% CI, 0.96-10.35) for infection by species group alpha-9 non-HPV16 oncogenic types but not species group alpha-5-7 non-HPV18 oncogenic types. Among women with an initial diagnosis of CIN2/3 at the first positive visit, CIN2/3 was more frequently redetected at the last positive visit for infections with, compared with without, high DNA load of species group alpha-9 non-HPV16 oncogenic types at both visits (P exact = 0.04). In agreement with data on baseline viral load, the viral load change-associated risk of CIN2/3 differs by HPV species groups. These findings underscore the importance of distinguishing species groups in future studies of clinical relevance of HPV DNA load.