Risk Factors for Non–Human Papillomavirus (HPV) Type 16/18 Cervical Infections and Associated Lesions Among HPV DNA–Negative Women Vaccinated Against HPV-16/18 in the Costa Rica Vaccine Trial

Background Factors that lead human papillomavirus (HPV) infections to persist and progress to cancer are not fully understood. We evaluated co-factors for acquisition, persistence, and progression of non–HPV-16/18 infections among HPV-vaccinated women. Methods We analyzed 2153 women aged 18–25 years randomized to the HPV-vaccine arm of the Costa Rica HPV Vaccine Trial. Women were HPV DNA negative for all types at baseline and followed for approximately 11 years. Generalized estimating equation methods were used to account for correlated observations. Time-dependent factors evaluated were age, sexual behavior, marital status, hormonally related factors, number of full-term pregnancies (FTPs), smoking behavior, and baseline body mass index. Results A total of 1777 incident oncogenic non–HPV-16/18 infections were detected in 12 292 visits (average, 0.14 infections/visit). Age and sexual behavior–related variables were associated with oncogenic non–HPV-16/18 acquisition. Twenty-six percent of incident infections persisted for ≥1 year. None of the factors evaluated were statistically associated with persistence of oncogenic non–HPV-16/18 infections. Risk of progression to Cervical Intraepithelial Neoplasia grade 2 or worst (CIN2+) increased with increasing age (P for trend = .001), injectable contraceptive use (relative risk, 2.61 [95% confidence interval, 1.19–5.73] ever vs never), and increasing FTPs (P for trend = .034). Conclusions In a cohort of HPV-16/18–vaccinated women, age and sexual behavior variables are associated with acquisition of oncogenic non–HPV-16/18 infections; no notable factors are associated with persistence of acquired infections; and age, parity, and hormonally related exposures are associated with progression to CIN2+.