Higher Expression of HPV16 Derived E7_LI Transcript Observed in Men With HIV and Recurrent Anal Cancer

Area of Science:

• Oncology
• Virology
• Immunology

Background:

• Squamous cell carcinoma of the anus (SCCA) affects people with HIV (PWH), particularly men who have sex with men (MSM).
• Anal cancer (AC) recurrence rates are high (approx. 25%) after standard chemoradiation therapy (CRT).
• Previous research indicated distinct immune gene expression in non-recurrent (NR) versus recurrent (R) AC, but the role of HPV and host interactions remains understudied.

Purpose of the Study:

• To investigate if specific human papillomavirus (HPV) genotypes and gene expression patterns differentiate between recurrent and non-recurrent anal cancer (AC).
• To explore correlations between viral (HPV) and host (human) immune mediators in AC.
• To identify potential therapeutic targets for reducing AC recurrence.

Main Methods:

• Bulk RNA sequencing data from 12 AC patients (9 NR, 3 R) were analyzed.
• VIRTUS 2 was used to detect and map viral RNA reads to identify HPV genotypes and expression.
• Correlation analysis was performed between HPV transcripts and host immune genes.

Main Results:

• HPV16 was the most prevalent high-risk HPV type (83% of tumors).
• A lower rate of a specific HPV16 polycistronic transcript (E7^L1) was observed in non-recurrent (NR) AC.
• HPV transcripts correlated directly with host genes involved in cell growth and inversely with genes regulating growth, proliferation, and immune response.

Conclusions:

• Concurrent analysis of viral and host factors in AC tumors provides insights into recurrence mechanisms.
• Specific HPV gene expression patterns and host immune responses are associated with AC recurrence.
• These findings suggest potential new therapeutic strategies targeting viral-host interactions to improve AC treatment outcomes.