A Study on the Impact of HPV Genotype Infection Patterns on the Occurrence of High-Grade Squamous Intraepithelial Lesion

Objective

To 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.

Methods

In 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.

Results

Single 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.

Conclusion

HPV16, 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.