Association of human papillomavirus integration with better patient outcomes in oropharyngeal squamous cell carcinoma.

Lisa M Pinatti
Hana N Sinha
Collin V Brummel
Christine M Goudsmit
Timothy J. Geddes, Beaumont Health
George D. Wilson, Beaumont Health
Jan A. Akervall, Beaumont Health
Chad J Brenner
Heather M Walline
Thomas E Carey


BACKGROUND: The molecular drivers of human papillomavirus-related head and neck squamous cell carcinoma (HPV + HNSCC) are not entirely understood. This study evaluated the relationship between HPV integration, expression of E6/E7, and patient outcomes in p16+ HNSCCs.

METHODS: HPV type was determined by HPV PCR-MassArray, and integration was called using detection of integrated papillomavirus sequences polymerase chain reaction (PCR). We investigated whether fusion transcripts were produced by reverse transcriptase polymerase chain reaction (RT-PCR). E6/E7 expression was assessed by quantitative RT-PCR. We assessed if there was a relationship between integration and E6/E7 expression, clinical variables, or patient outcomes.

RESULTS: Most samples demonstrated HPV integration, which sometimes resulted in a fusion transcript. HPV integration was positively correlated with age at diagnosis and E6/E7 expression. There was a significant difference in survival between patients with vs without integration.

CONCLUSIONS: Contrary to previous reports, HPV integration was associated with improved patient survival. Therefore, HPV integration may act as a molecular marker of good prognosis.