From HPV genotypes to cervical lesion burden: public health-relevant heterogeneity across 1.29 million screening records in Guangdong, China.

Objective: To characterize the association between reported human papillomavirus (HPV) genotype detection patterns with cervical lesion burden and to assess variation by region, year, age, reported prior screening history, and diagnostic category in a province-wide cervical cancer screening program in Guangdong, China. Methods: We conducted a screening program-based cross-sectional study using 1,291,583 individual-level screening records collected during 2017-2022. Aggregate lesion data from Guangzhou, Dongguan, and Zhongshan supplemented city- and region-level lesion analyses. Genotype-specific analyses included 1,244,766 records with genotype-level results. Joinpoint regression and adjusted generalized linear models were used to assess temporal and age-related patterns. Sensitivity analyses retained only the earliest eligible record for each identifiable woman. Results: High-risk HPV was detected in 63,004 records (4.88%). Low-grade squamous intraepithelial lesions (LSIL), high-grade/microinvasive cervical lesions, and cervical cancer were recorded in 11,106 (0.86%), 6,633 (0.51%), and 382 (0.03%) records, respectively. The cities with the highest pooled proportions differed across lesion categories. Overall low-risk and high-risk HPV positivity showed significant positive annual percentage changes of 19.21 and 8.05%, respectively, whereas no individual high-risk genotype changed significantly. High-risk HPV positivity was highest in Northern Guangdong (5.6%), and HPV16 was the most frequently reported genotype in all four regions. Compared with participants aged <45 years, those aged ≥65 years had adjusted relative risks of 1.52 (95% CI, 1.22-1.91) for high-grade/microinvasive cervical lesions, 5.02 (2.43-10.35) for cervical cancer, and 1.51 (1.39-1.63) for high-risk HPV positivity. Age-related differences in severe lesions were more evident among records with no prior screening reported. The detection proportion of HPV16 increased from 28.6% in LSIL to 50.0% in high-grade/microinvasive cervical lesions and 69.3% in cervical cancer. HPV18 ranked second in cancer (18.3%), whereas HPV52 and HPV58 were more frequent in LSIL and high-grade/microinvasive lesions. Conclusion: This province-wide screening study linked reported HPV genotype patterns with cervical lesion burden and identified uneven disease burden across Guangdong, a higher burden of severe cervical lesions among older participants with no prior screening reported, and distinct genotype-specific detection patterns across lesion grades. These findings support locally adapted screening and follow-up strategies that prioritize high-burden regions, under-screened older women, and genotype-informed follow-up of HPV-positive women.