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

## TL;DR

This study found that a specific HPV16 gene transcript is more active in men with HIV who experience recurring anal cancer, suggesting a link between viral gene activity and cancer recurrence.

## Contribution

The study identifies a novel association between HPV16 E7_LI transcript expression and anal cancer recurrence in HIV-positive men.

## Key findings

- HPV16 was detected in 83% of anal cancer tumors, with higher recurrence rates in low-risk HPV types.
- The E7_LI transcript was significantly more active in recurrent tumors compared to non-recurrent ones.
- Human genes involved in growth and immune response showed direct or inverse correlations with HPV gene expression.

## Abstract

Squamous cell carcinoma of the anus (SCCA) or anal cancer (AC) is an understudied cancer with a high occurrence rate in people with HIV (PWH), especially men having sex with men (MSM). Furthermore, AC recurs in approximately one‐fourth of patients who undergo standard care with chemoradiation therapy (CRT). Using bulk RNA sequencing data of AC obtained from 12 patients with non‐recurrent (NR, N = 9) or recurrent (R, N = 3) cancer, we previously showed upregulated expression of key immune genes in the NR compared to the R group. Although the main causative agent of AC is high‐risk human papillomavirus (HPV), association of host and viral RNA transcript expression contributing to AC recurrence has not been extensively studied. The objective of the current study was to determine whether enrichment of specific HPV genotypes and/or HPV gene expression patterns differentiate the two groups and if any specific viral (HPV) and host (human) immune mediators correlate with each other. Using bulk RNA sequencing data and VIRTUS 2, we detected viral RNA reads mapping to seven high‐risk and six low‐risk HPV types, of which the high‐risk HPV16 observed in 83% (10/12) AC tumors (7/9 NR and 3/3 R). Rate of all HPV genomes trended toward a decrease in NR AC isolates and correlation between HPV types was more commonly observed in low‐risk ones. Analysis of HPV 16 gene expression profile showed a significantly lower positivity rate for a polycistronic transcript encoding for E7^L1 in the NR group (1/9, NR vs. 3/3, R, p < 0.05). An unbiased correlation analysis of HPV‐human transcript expression showed a direct correlation between HPV transcripts and human genes involved in cell growth. The data also identified human transcripts showing an inverse correlation with HPV gene expression. These included genes involved in negative regulation of growth, proliferation, and immune response. Taken together, these data indicate that concurrent analyses of viral and host factors in the same tumor can identify potential new therapeutic targets to ameliorate cancer recurrence post‐treatment.