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Background Persistent high-risk human papillomavirus infection precedes the development of cervical cancer. Here we evaluated the contribution of HPV16/18 viral load and the presence of infections with multiple HPV types to persistence and clearance of HPV16/18 infections. Methods Vaginal self-swabs were obtained from young women (16–29 y) with one year interval. HPV genotyping was performed using the highly sensitive SPF10-DEIA-LiPA 25 system. HPV16/18 DNA loads were quantified via an adapted, highly sensitive qPCR protocol targeting the L1 gene. Results We identified 227 HPV16 and 111 HPV18 infections with follow-up. For HPV16 132/227 (58%) were persistent and 95/227 cleared. For HPV18 49/111 (44%) infections were persistent and 62/111 cleared. Baseline viral load was significantly higher in persistent infections than in clearing infections for both HPV16 (p = 0.022) and HPV18 (p = 0.013). At baseline, only HPV16 viral load was significantly higher in multiple HPV infections compared with single infections (p = 0.003). In logistic regression analysis HPV16 and HPV18 viral load were found to contribute to persistency with OR = 1.279 (95%CI = 1.074–1.524) and OR = 1.256 (95%CI = 1.028–1.533) per log-unit increase HPV16 and HPV18 viral load respectively. The presence of multiple HPV type infections was not associated with higher persistency. Conclusion HPV16/18 viral load might be used as a marker for persisting infections and is affected by the presence of multiple HPV infections. Evaluation of these parameters at the population level may be of value to assess the presence of persistent or clearing HPV16/18 infections as an early marker, and may provide useful quantitative information in (epidemiological) vaccine monitoring studies. [ABSTRACT FROM AUTHOR]