Identification of HPV genotypes causing cervical precancer using tissue-based genotyping.

Area of Science:

• Gynecology
• Oncology
• Virology

Background:

• Accurate identification of high-risk human papillomavirus (hrHPV) genotypes is crucial for cervical precancer management and HPV vaccine development.
• Co-infections with multiple hrHPV types are common and complicate the assessment of carcinogenicity, necessitating precise genotype attribution.

Purpose of the Study:

• To determine the causal hrHPV genotypes in cervical precancers (CIN2+) using tissue-based genotyping.
• To compare the accuracy of different genotype attribution models (hierarchical and proportional) against tissue-based findings.

Main Methods:

• Tissue-based genotyping (whole tissue sections and laser-capture microdissection) was performed on cervical precancers (CIN2+).
• Over 1,800 HPV genotyping assays were conducted on samples from women with multiple hrHPV detections in cytology.
• Genotype attribution from tissue analysis was compared to established models.

Main Results:

• Of 114 women with genotyping data, 94 had hrHPV detected in tissue.
• Seventy-one women (75.5%) had a single causal hrHPV genotype, while 23 (24.5%) had multiple causal hrHPV genotypes.
• Ten women had multiple causal infections within a single biopsy, contradicting the single-type causation theory.

Conclusions:

• HPV16 was the predominant genotype, but attribution models showed bias, overattributing HPV16 and underattributing HPV18 and HPV35.
• Accurate identification of all causal hrHPV genotypes is essential for evaluating vaccine efficacy, understanding unmasking effects, and refining risk assessment strategies.