A Study on the Impact of HPV Genotype Infection Patterns on the Occurrence of High‐Grade Squamous Intraepithelial Lesion
ABSTRACTObjectiveTo investigate the differential risk of high‐grade squamous intraepithelial lesion or worse (HSIL+) associated with single versus co‐infection patterns of high‐risk human papillomavirus (HR‐HPV) genotypes.MethodsIn this retrospective cohort study, 10,570 patients with abnormal ThinPrep cytology test results and/or HR‐HPV infection who underwent colposcopy‐guided cervical biopsy at Wuhan Children's Hospital (May 2021–May 2023) were enrolled. Histopathological diagnosis served as the gold standard. Multivariate logistic regression was used to analyze HSIL+ risk across HPV infection patterns, adjusting for age and viral load.ResultsSingle infections with HPV31, HPV33, or HPV58 demonstrate comparable positivity rates of HSIL+ to HPV16 monoinfection. After adjusting for confounders, logistic regression revealed that co‐infection of HPV16 with low‐risk HPV genotypes reduced the risk of progression to HSIL+ compared to HPV16 monoinfection (p < 0.05). Similarly, co‐infections involving HPV33 or HPV58 (regardless of high/low‐risk partners) were associated with lower HSIL+ risk (all p < 0.05). In contrast, HPV31 demonstrated consistent HSIL+ risk irrespective of co‐infection status.ConclusionHPV16, HPV31, HPV33, or HPV58 need equivalent clinical vigilance in screening and management protocols. Co‐infection with low‐risk HPV genotypes attenuates HSIL+ risk in HPV16‐infected individuals, and HPV33/58 co‐infections (with any genotype) exhibit protective effects. Our study suggests that HPV31‐associated risk might remain unaffected by co‐infection, suggesting genotype‐specific biological interactions. These findings highlight the importance of genotyping‐guided risk stratification in cervical cancer screening.