Early natural history of incident, type-specific human papillomavirus infections in newly sexually active young women

Abstract

Background: Characterizing short-term detection patterns of young women's incident α-genus human papillomavirus (HPV) infections may further our understanding of HPV transmission.

Methods: Between 2000 and 2007, we followed 18- to 22-year-old female university students with triannual HPV DNA and Papanicolaou testing. Using Kaplan-Meier methods, we estimated duration of detectable, type-specific incident infections; time to redetection (among infections that became undetectable); and time to cervical lesion development after incident infection. We evaluated risk factors for short-term persistent versus transient infection with logistic regression.

Results: Three hundred three incident, type-specific infections were detected in 85 sexually active women. Median time to first negative test after incident infection was 9.4 (95% CI: 7.8-11.2) months; 90.6% of infections became undetectable within 2 years. About 19.4% of infections that became undetectable were redetected within 1 year. Cervical lesions were common and 60% were positive for multiple HPV types in concurrent cervical swabs. Incident HPV detection in the cervix only (vs. the vulva/vagina only or both sites) was associated with short-term transience.

Conclusions: Although most incident infections became undetectable within 2 years, redetection was common. Cervical lesions were a common early manifestation of HPV infection.

Impact: It remains unclear whether potentially modifiable risk factors can be identified to reduce infection duration (and transmission likelihood).

Figure 1

Percentage of persistently-detected type-specific HPV infections, after incident type-specific HPV detection (n=257 type-specific HPV infections). A failure was defined as the first type-specific negative test after the incident positive test. Infections were censored at the last follow-up visit or the date of treatment for CIN 2+.

Figure 2

Cumulative probability of re-detecting type-specific HPV, after the first negative test following incident detection (n=173 type-specific infections).

Figure 3

Patterns of type-specific high-risk HPV DNA detection in sexually active young women. Each row represents an incident type-specific HPV infection characterized by a detection pattern that included intercurrent negative tests between two or more positive tests. Visit number is in relation to the first detection of type-specific HPV DNA (visit 0) (e.g. visit 5 refers to the 5^th visit after first detection of type-specific HPV DNA). A gray box indicates type-specific HPV detection in at least one genital sample. A white box indicates that all samples were negative for the specific HPV type. Black indicates the end of study follow-up.

Figure 4

Cumulative probability of developing cervical SIL among women with incident HPV infection at any site (thick black line; n=82 sexually active women with incident HPV infection at any site; three sexually active women who developed cervical SIL prior to first incident HPV detection were excluded from the analysis) and women with incident HPV infection at the cervix (thin black line; n=73 women with incident HPV infection at the cervix [ignoring any HPV results from previously collected vulvar/vaginal samples]; three sexually active women who developed cervical SIL prior to first incident cervical HPV detection were excluded from the analysis). Of 27 cases of newly-detected cervical SIL, 25 were low-grade and 2 were high-grade. Eleven of the 25 women with LSIL were subsequently referred for colposcopically-directed biopsy; 2 women had biopsy-confirmed CIN 2 (1 woman had biopsy-confirmed CIN 3 diagnosed by her primary care provider). One of the 2 women with HSIL had biopsy-confirmed CIN 2 diagnosed at a subsequent visit. The time between first incident HPV infection (at any site) and CIN 2 or CIN 3 ranged from 4 to 32 months.

Figure 5

Distribution of the number of HPV types detected in the cervical swab sample collected at the same visit as the first SIL diagnosis (n=30).