Clinical study on the pathogenic risks of different genotypes of high-risk HPV infection and multiple infections

OBJECTIVE: To investigate the oncogenic risks of distinct high-risk human papillomavirus (HR-HPV) genotypes and whether multiple infections exacerbate pathogenicity, with analysis of age stratification and viral load impact. METHODS: Clinical and pathological data from 2,525 patients undergoing colposcopy-directed biopsy for cervical abnormalities (2020-2023) were analyzed. HPV genotyping (18 types) and viral load quantification (Ct-values) were performed using PCR-membrane hybridization. Histopathology (CC/LSIL/HSIL/SCC) was evaluated by blinded experts. Statistical analyses included age stratification (< 35 vs. ≥35 years) and multivariate adjustment for viral load (Ct ≤ 30). RESULT: HR-HPV single-type infections predominated (1,774 cases, 70.26%), with genotype distribution: 16 (17.98%), 52 (10.50%), 58 (7.88%), 53 (4.63%), and 18 (4.55%). Multiple infections occurred in 474 cases (18.77%). Versus HPV-negative/low-risk controls, the highest pathogenic risks were: type 16 (OR = 7.96, 95% CI:5.41-11.71), type 58 (OR = 5.80, 95% CI:3.75-8.99), multiple infections (OR = 5.02, 95% CI:3.42-7.37), type 18 (OR = 4.86, 95% CI:2.95-8.02), and type 35 (OR = 4.07, 95% CI:1.82-9.10) (all P = 0.001). Age ≥ 35 years independently increased HSIL + risk (OR = 2.16, 95% CI:1.62-2.88, P = 0.001), with HPV16/18/35 showing significantly higher ORs in this group. High viral load (Ct ≤ 30) independently predicted HSIL + progression (OR = 2.98, 95% CI:1.92-4.63, P = 0.001). Multiple infections did not increase risk for genotypes 16/18/33/35/52/56/58/68 versus single infections, except for HPV51 (P = 0.01). CONCLUSION: Genotype 16 demonstrates the strongest oncogenic potential, with pathogenic hierarchy: 16 > 58 > 18 > 35. Multiple infections do not synergistically increase risk for dominant genotypes. Age ≥ 35 years and high viral load (Ct ≤ 30) independently elevate cervical lesion severity, supporting their integration into risk-stratified screening protocols. CLINICAL TRIAL NUMBER: Not applicable.