Introduction: Vaccination against low-risk human papillomavirus (HR-HPV) types 6 and 11, which cause genital warts, and against high-risk human papillomavirus (HR-HPV) types 16 and 18, which are responsible for 70% of cervical cancers, was introduced in France in 2008. Understanding the characteristics of HPV infection and the distribution of genotypes in cervical smears among unvaccinated women is a necessary prerequisite for assessing the impact of vaccination on viral ecology and associated cervical lesions. Materials and methods: residual samples from 6,539 Pap smears were collected as part of organized screening trials conducted in four French regions. The samples were stratified according to the women’s age and Pap test results. The specimens were analyzed using the PapilloCheck® genotyping kit, which identifies 18 high-risk HPV (HR-HPV) and 6 low-risk HPV (LR-HPV) types. Results: The age-standardized prevalence of HPV 16/18 infection (with or without other oncogenic HPV types) was 47.2% (95% confidence interval, 95% CI: [42.4–52.1]) in high-grade lesions (HSIL), 20.2% in low-grade lesions (LSIL) (95% CI: [16.7–23.7]), and 3.9% [2.8–5.1] in normal smears. HR-HPV was detected in 13.7% [11.7–15.6] of normal smears. HPV 16/18 were detected in 64% of high-grade lesions (HSIL) in women under 30 years of age. HPV 16 was detected in 54% (27/50) of invasive cervical cancers, including 5 adenocarcinomas. Conclusion: HPV 16 was frequently found in HSIL and cancers. The high prevalence of HPV 16/18 infection among women under 30 years of age with HSIL suggests that the impact of vaccination will first be observed in young women. (R.A.)