Rapid clearance of human papillomavirus and implications for clinical focus on persistent infections

Abstract

Health professionals and the public need to understand the natural history of human papillomavirus (HPV) infections of the cervix to best use the information provided by new molecular screening tests. We investigated outcomes of 800 carcinogenic HPV infections detected in 599 women at enrollment into a population-based cohort (Guanacaste, Costa Rica). For individual infections, we calculated cumulative proportions of three outcomes (viral clearance, persistence without cervical intraepithelial neoplasia grade 2 or worse [CIN2+], or persistence with new diagnosis of CIN2+) at successive 6-month time points for the first 30 months of follow-up. Cervical specimens were tested for carcinogenic HPV genotypes using an L1 degenerate-primer polymerase chain reaction method. Infections typically cleared rapidly, with 67% (95% confidence interval [CI] = 63% to 70%) clearing by 12 months. However, among infections that persisted at least 12 months, the risk of CIN2+ diagnosis by 30 months was 21% (95% CI = 15% to 28%). The risk of CIN2+ diagnosis was highest among women younger than 30 years with HPV-16 infections that persisted for at least 12 months (53%; 95% CI = 29% to 76%). These findings suggest that the medical community should emphasize persistence of cervical HPV infection, not single-time detection of HPV, in management strategies and health messages.

Figure 1

Clearance of carcinogenic human papillomavirus (HPV) infections during 30 months of follow-up. (A) All ages combined (n = 800 infections). (B) Women younger than 30 years (n = 393 infections). (C) Women aged 30 years or older (n = 407 infections). Carcinogenic types include HPV types 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68, 73, 82, 82v. The x-axes represent months of follow-up, and the y-axes represent the percentage of infections that cleared (unshaded), persisted without evidence of cervical intraepithelial neoplasia grade 2 or worse (CIN2+; stippled), or persisted with evidence of CIN2+ (solid shading). The 3-month data represent nonrandom samples (36% for A, 38% for B, and 34% for C).

Figure 2

Clearance of human papillomavirus type 16 infections during 30 months of follow-up. (A) All ages combined (n = 115 infections). (B) Women younger than 30 years (n = 55 infections). (C) Women aged 30 years or older (n = 60 infections). The x-axes represent months of follow-up, and the y-axes represent the percentage of infections that cleared (unshaded), persisted without evidence of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) (stippled), or persisted with evidence of CIN2+ (solid shading). The 3-month data represent nonrandom samples (38% for A, 44% for B, and 33% for C).