Incidence, clearance and predictors of human papillomavirus infection in women

Abstract

Background: Persistent infection with carcinogenic human papillomavirus (HPV) is linked to high-grade lesions and cervical cancer. To better understand the natural history of HPV, we sought to determine the rates of incident and cleared carcinogenic HPV infection, by age, among women aged 15-49 years and to explore risk factors for incident infection.

Methods: Women enrolled in an earlier HPV prevalence survey (500 of 800 who were HPV-negative and all 121 who were HPV-positive) were invited to participate in follow-up HPV testing at their periodic health examination one year later. A cervical soft-brush specimen for HPV testing and a smear for cytologic examination were obtained, and participants completed a questionnaire on their demographic characteristics and sexual history.

Results: Two hundred and fifty-three (50.6%) previously HPV-negative women and 54 (44.6%) previously HPV-positive women were retested. The mean interval between visits was 14.0 (standard deviation 2.0, median 13.5, range 9.0-21.3) months. Incident HPV infection occurred in 11.1% (28/253) of the women overall, with the highest rate, 25.0% (6/24), in the 15-19-year age group. In the univariate analyses, risk factors for incident HPV were the median number of sexual partners in the past year (< or = 1 v. > or = 2: odds ratio [OR] 8.2, 95% confidence interval [CI] 3.0-22.2; p < 0.001) and the median number of sexual partners over a lifetime (> 3 v. < or = 3: OR 3.0, 95% CI 1.2-7.2; p = 0.014). In multivariate logistic regression modelling adjusted for age, median number of sexual partners in the past year, median number of sexual partners over a lifetime, marital status, current smoking and current use of oral contraceptives, only the median number of sexual partners in the past year remained significantly associated with incidence (OR 6.2, 95% CI 1.6-24.5; p = 0.009). Of the previously HPV-positive women, 51.9% (28/54) had cleared the infection.

Interpretation: Incident infection with carcinogenic HPV was highest in women aged 15-19 years, and risk factors were consistent with a sexually transmitted infection. A large proportion of the women who were HPV-positive appeared to have cleared the infection after one year.

Fig. 1: Flow diagram showing how 253 HPV-negative and 54 HPV-positive women were recruited for 1-year follow-up from among those who had been enrolled in our previous population-based survey of HPV prevalence in Ontario. *HPV-positivity for follow-up purposes was determined by the hybrid capture II (HCII) assay (Digene Corporation, Gaithersburg, Md.). †HPV-negative women were found to be negative by both HCII and polymerase chain reaction (PCR) testing; PCR testing indicates the presence of any type of HPV, and genotyping may be used to identify carcinogenic types. ‡Practices that withdrew from the study or discontinued recruitment. §Women were considered lost to follow-up if they refused to participate in the follow-up survey, did not have the physicians' office procedures (no study samples taken at visit for cervical cytology and/or or no appointment within 3 months of Pap test), changed physicians, did not attend their appointment, could not have Pap test (third trimester of pregnancy or recent childbirth), could not be contacted or had no reason/contact recorded (practices did not complete follow-up for lists provided). ¶Several samples were lost or improperly stored and/or questionnaires were not completed by patients or forwarded by the practices.

Figure 2: Age-specific incidence and clearance rates for carcinogenic types of HPV determined by the hybrid capture II (HCII) assay performed at a follow-up visit after an average interval of 14 months on 253 women who had been negative for HPV by both the HCII assay and PCR testing (incidence) and 54 who had been positive by the HCII assay (clearance).