The utility of fibroblast co-culture for the maintenance of episomes in human papillomavirus-associated cancer models

TL;DR

This paper shows that fibroblast co-culture can help maintain episomal HPV16 genomes in cancer models, which are otherwise unstable in standard monoculture.

Contribution

The study introduces fibroblast co-culture as a novel method to preserve episomal HPV16 in OPC cancer models.

Findings

UMSCC104 cells rapidly lose episomal HPV16 and integrate the genome in monoculture.

Later lots of UMSCC104 cells are fully integrated, resolving prior inconsistencies.

Fibroblast co-culture supports episomal maintenance and genome stability in HPV+ models.

Abstract

Human papillomavirus-associated head and neck squamous cell carcinomas (HPV+ HNSCCs) lack early diagnostics and continue to rise in incidence. HPV16 has been detected in ~90% of HPV+ oropharyngeal cancers (HPV+ OPCs), an anatomical subset of HNSCC, with the majority retaining episomal viral genomes. Despite this, existing episomal HPV16+ OPC cell lines are especially scarce. UMSCC104s were initially reported as episomal; however, the literature contains conflicting reports regarding the genome status of these cells. We now show that UMSCC104s rapidly undergo integration and E2 loss under standard monoculture, and later lots are fully integrated. These findings resolve prior discrepancies and underscore the instability of episomes in monoculture. Accurate models of HPV-driven cancers are critically needed. We propose fibroblast co-culture methods, traditionally utilized for HPV+ keratinocyte models, as a strategy to preserve episomal status in cancer models by supporting viral and host genome stability.

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