Human papillomavirus type 18 variants: histopathology and E6/E7 polymorphisms in three countries

Area of Science:

• Oncology
• Virology
• Pathology

Background:

• Human papillomavirus (HPV) types 16 and 18 are key drivers of cervical cancer.
• HPV 16 is typically associated with squamous cell carcinomas (SCCs), and HPV 18 with adenocarcinomas (ADCs).
• Geographic variations in HPV intratypic variants exist, but their association with tumor histology is less understood.

Purpose of the Study:

• To investigate if geographically distinct HPV intratypic variants correlate with specific cervical cancer histological subtypes (ADCs vs. SCCs).
• To determine the association between HPV 18 intratypic variants and cervical ADC/SCC.
• To explore potential links between HPV 16 intratypic variants and cervical cancer histology.

Main Methods:

• Histological classification of 44 HPV 18-positive and 91 HPV 16-positive cervical carcinomas using H&E, PAS, and Alcian Blue staining.
• Sequencing of HPV samples to classify intratypic variants into known phylogenetic branches.
• Analysis of HPV 18 E6 and E7 open reading frames for amino acid changes.

Main Results:

• The Asian Amerindian HPV 18 variant was significantly more prevalent in ADCs (56%) than SCCs (15%) (p < 0.006).
• The African HPV 18 variant was exclusively identified in SCCs.
• No specific association was found between HPV 16 intratypic variants and tumor histopathology.
• Limited amino acid changes were detected in HPV 18 E6/E7, with two consistent changes in the African variant.

Conclusions:

• HPV 18 intratypic variants show differential associations with cervical adenocarcinoma and squamous cell carcinoma.
• These findings highlight the biological significance of intratypic HPV variants in cervical cancer pathogenesis.
• Understanding these variant-specific associations may help explain differences in ADC and SCC development.