Objectives: This study aimed to describe the study design, and to analyze the type-specific distribution of cervical high-risk human papillomavirus (hrHPV) infection and its association with cytological and histological results in a large population-based screening program in Buji Street, Shenzhen, China. Methods: A total of 10,186 women aged 21-70 years were co-tested by Cobas4800 HPV assay and liquid-based cytology. Women were referred to colposcopy by virtue of being HPV16/18-positive, Other hrHPV-positive/ cytology ≥ASCUS, or HPV-negative/ cytology ≥LSIL. Three-year histological follow-up data were recorded. Results: The overall prevalence of hrHPV infection was 11.1%; among them, the highest type was Other hrHPV (8.9%), followed by HPV16 (1.6%) and HPV18 (0.6%). Moreover, the prevalence of hrHPV and that of HPV16 increased with cytological severity (P_trend <0.001). In the baseline phase, 106 women had cervical intraepithelial neoplasia 2/3 (CIN2/3) and six had cervical cancers. During 3-year follow-up, 12 cases of CIN2/3 and no cancers were identified. For HPV16-positive women with normal cytology, the baseline risks of CIN2/3 or worse (CIN2+/CIN3+) were 15.5% (7.0-23.9%) and 4.2% (1.4-8.5%) respectively. For Other hrHPV-positive women with normal cytology, the cumulative 3-year risks of CIN2+/CIN3+ were 3.1% (1.0-5.2%) and 0.7% (0.3-2.1%) respectively. Strikingly, 75.8% (322/425) of abnormal cytology and 50.9% (29/57) HSIL cytology were attributed to Other hrHPV infection in HPV-positive women. Similarly, Other hrHPV infection led to large proportions of CIN2 (62.7%) and CIN3+ (43.9%) over 3-year follow-up. Conclusions: The co-testing modality is a feasible, effective and safe option for cervical cancer screening in urban population. Great importance should also be attached to 'genotypes excluding HPV16/18' and separate detection of each genotype when considering screening and vaccination strategy.

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