Acquisition of new infection and clearance of type-specific human papillomavirus infections in female students in Busan, South Korea: a follow-up study

More than half of sexually active women worldwide are infected by one or more genital human papillomavirus (HPV) types at some point in time [1], and the three-year cumulative incidence of HPV infection among young women in some Western countries is over 40% [2–4]. Although HPV infection is very common, 50% to 77% of HPV-positive women in cohort studies have been shown to clear the infection spontaneously in one year's time [1, 2, 5–8]. No studies, however, have investigated type-specific HPV incidence and clearance in Asian women. Hence, we followed up a group of female students in Busan, Republic of Korea, who had been evaluated for HPV prevalence one and a half years earlier [9].

The prevalence of HPV infection in female students in Busan, Korea, at baseline was 15.2% [9]. In the follow-up study, 17.5% of 171 students at risk who were HPV-negative at baseline became positive. Reinfection with a new HPV type was also frequent (50% of 26 HPV-positive students). The acquisition of new HPV infections was approximately 30% in women who became sexually active or changed sexual partner during the follow-up period. Interestingly, 13% of the 118 students who reported that they never had penetrative sexual intercourse became HPV-positive at follow-up. Modes of HPV transmission, besides penetrative sexual intercourse, have been suggested [4, 11], but, although the questionnaire was self-administered and full confidentiality was assured, we cannot rule out inaccuracies in the reporting of sexual behavior. In addition, there may be a possibility to be contaminated or false positive for HPV test of the samples with never having a penetrative sexual intercourse, even though it is very little or rare.

Acquisition of new HPV infection is common, particularly among sexually active young women, and the incidence appears to be higher for oncogenic than for non-oncogenic types [6, 12]. A prospective study in Brazilian women showed that there were 1.3% new infections per month, with 38% cumulative positivity after one and a half years [5]. In Canadian university students, the incidence rate was 1.9% per month, and the cumulative rate was 18.0% at one year and 36.4% at two years of follow-up [12]. In another study of Canadian women, the overall infection incidence was 11.1% per year, with the highest rate (25.0%) in the 15–19-year age group [8]. The rate of new HPV infections in young women in the United States was 2.9% per month [6], and the three-year cumulative incidence was over 40% [2–4, 11]. In our study, the rate of acquisition of new infections for any HPV type per 1000 woman-months was estimated as 9.8 (95% CI: 6.6–14.0) (data not shown). Considering the longer follow-up interval than other studies, this study suggests that HPV incidence in Korean female students is relatively lower than that in corresponding populations in Western countries.

Current knowledge on the relationship between smoking and incidence of HPV infection is limited, with previous studies reporting inconsistent results [11, 13, 14]. In our baseline study, smoking was one of the strongest risk factors for HPV-positivity in female students (ever-smokers vs. never-smokers, OR = 3.8; 95% CI: 1.9–7.5) [9]. In current follow-up study, smoking was again a predictor of HPV incidence, although, after adjustment for changes in sexual habits, the association was not statistically significant. Moreover, clearance of HPV infection was more frequent in women who never smoked than in women who ever smoked, but the association was not statistically significant (data not shown).

HPV infection is common, but it is highly transient. In our study, 80% of infections cleared and 77% of students who were HPV-positive at baseline became negative for the HPV type(s) present at baseline after one and a half years. Other studies also showed that the majority of HPV infections clear after one or two years [2, 5–8, 12, 15]. In a population-based five-year follow-up study in Colombian women, 77% of HPV infections cleared after one year and 93% cleared after five years; clearance was most frequent in the first six months of follow-up [7]. Other cohort studies also show 50%–75% clearance of HPV infections after one year [2, 5, 6, 8].

A self-collected Dacron swab sample of cervicovaginal cells is a technically feasible alternative to clinician-administered cervical cell collection in natural history studies of HPV and cervical cancer [16]. Our previous study, the baseline study, also showed that almost self-collected cervicovaginal samples were very adequate for test (β-globin positive in 99.1% of female students) [9].

Our current study has strengths and weaknesses. It is the first study to apply self-collection of cervico-vaginal cells and a very sensitive HPV testing method in a follow-up study that included many virgins, and to show high rate of acquisition of new HPV infection in young Asian women. The HPV testing method that we used at baseline and also at follow-up was highly sensitive but there could be undetected infections. New infections could be infections that were previously there and were missed, and cleared infections could be due to errors in the follow-up sample. However, these limitations are also important in this study as other studies.

Unfortunately, despite repeated efforts, traceability and compliance among female students was low. Only 57% (381/671) of female students were available to contact and 52% (197/381) of those who contacted, participated this study. Furthermore, there were only 36 baseline infections available for the analysis of clearance. Thus, there was limitation to detect significant associations between risk factors and HPV acquisition or clearance. However, when we compared the characteristics (i.e., age, HPV positivity, sexual, smoking and alcohol drinking habits at baseline) of study subjects who were and were not included in the follow-up study, they did not differ significantly (Table 1). Moreover, based on the Korean National Health and Nutrition Survey and other studies [17, 18], the health behaviors (i.e., smoking and alcohol drinking habits and sexual intercourse) of study participants were similar to those of any other Korean girls of these ages. Therefore our present findings on HPV acquisition and clearance are not highly biased.

In summary, we investigated acquisition and clearance of HPV infection with 197 followed-up female students in Busan, Korea. This study shows that the acquisition of new HPV infection among young women in the Republic of Korea was high and also the clearance was frequent. Self-collection of cervicovaginal cells is applicable to follow-up studies that include virgins.