Journal
EUROPEAN JOURNAL OF CANCER
Volume 67, Issue -, Pages 141-151Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.ejca.2016.08.012
Keywords
Human papillomavirus; Oropharyngeal carcinoma; Cell-mediated immunity; Interferon-gamma
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Funding
- Cancer Research UK [A14962]
- Addenbrookes Charitable Trust [KDD/9478]
- Rosetrees Trust [M229-CD1] Funding Source: researchfish
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Introduction: Immunological response to human papillomavirus (HPV) in the development and progression of HPV16+ oropharyngeal squamous cell carcinoma (OPSCC) (accounting for the majority of viral associated cases) is largely unknown and may provide important insights for new therapeutic strategies. Methods: In this prospective clinical trial (UKCRN11945), we examined cell-mediated immune responses to HPV16 E2, E6 and E7 in peripheral blood using IFN-gamma enzyme-linked immunosorbent spot assay. CD56(+), CD4(+), CD8(+) and regulatory T cell frequencies were also discerned by flow cytometry. Fifty-one study participants with oropharyngeal carcinoma were recruited. Control subjects were those undergoing tonsillectomy for benign disease. All patients were treated with curative intent by radiotherapy chemotherapy. Disease-specific survival was investigated by multivariate analysis. Results: HPV16 DNA was detected in 41/51 of the OPSCC participants. T cell responses against HPV16 E6 or E7 peptides were detected in 33/51 evaluable patients, respectively and correlated with HPV status. Matched pre- and post-treatment T cell responses were available for 39/51 OPSCC cases. Within the whole cohort, elevated post-treatment CD8+ response to HPV16 E7 correlated with longer disease free survival (multivariate DFS p < 0.03). Within the HPV + OPSCC cohort, a significant increase in regulatory T cells (p < 0.02) was noted after treatment. Conclusions: This is the first study to provide survival data in OPSCC stratified by cell-mediated immune response to HPV16 peptides. Within the HPV16+ OPSCC cohort, enhanced immunoreactivity to antigen E7 was linked to improved survival. An increase in regulatory T cell frequencies after treatment may suggest that immunosuppression can contribute to a reduced HPV-specific cell-mediated response. (C) 2016 Elsevier Ltd. All rights reserved.
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