TTV Load Mirrors Local Immunity and Tracks HPV Positivity in the Anogenital Tract

Area of Science:

• Virology and Immunology
• Biomarker Discovery
• Human Papillomavirus (HPV) Research

Background:

• Torquetenovirus (TTV) load is a proposed immunomodulated biomarker.
• Its behavior in situ within HPV-infected mucosa is not well understood.
• Understanding TTV's role can offer insights into host immune responses to HPV.

Purpose of the Study:

• To investigate the association between in situ TTV load and HPV positivity.
• To explore the relationship between TTV load and HPV genotype complexity and risk.
• To evaluate TTV as a potential indicator of mucosal immunocompetence in HPV infections.

Main Methods:

• Retrospective cross-sectional study of 220 patients undergoing HPV screening (cervical swabs and anal brushings).
• HPV genotyping using Allplex™ HPV28.
• TTV load quantification by in-house RT-qPCR (log10 copies per 20 ng DNA).
• Statistical analyses included Mann-Whitney tests and logistic regression.
• Genotype co-occurrence analyzed using heatmaps and network analysis.

Main Results:

• TTV load was significantly higher in HPV-positive subjects (p < 0.01).
• Each 1-log10 increase in TTV was associated with a 60% increase in odds of HPV positivity (OR = 1.60, p = 0.022).
• TTV load increased with greater HPV genotype richness and was higher in high-risk (HR) HPV infections compared to low-risk (LR) infections (p < 0.01).
• Recurrent HPV genotype combinations and central genotypes were identified.

Conclusions:

• In situ TTV quantification is associated with HPV positivity and HPV genotype complexity/risk.
• TTV load demonstrates local predictive power for HPV infection status.
• Findings support TTV as an indirect indicator of mucosal immunocompetence in the context of HPV infection.