Stromal infiltration of CD8 T cells is associated with improved clinical outcome in HPV-positive oropharyngeal squamous carcinoma

Patients with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) have a better prognosis than those with HPV-negative tumours. There is interest in de-escalating their treatment but strategies are needed for risk stratification to identify subsets with a poor prognosis...

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Bibliographic Details
Published in:British journal of cancer 2015-09, Vol.113 (6), p.886-893
Main Authors: Oguejiofor, K, Hall, J, Slater, C, Betts, G, Hall, G, Slevin, N, Dovedi, S, Stern, P L, West, C M L
Format: Article
Language:English
Subjects:
Actins - analysis
Antigens, Neoplasm - analysis
Biopsy
Carcinoma, Squamous Cell - immunology
Carcinoma, Squamous Cell - mortality
Carcinoma, Squamous Cell - pathology
Carcinoma, Squamous Cell - radiotherapy
Carcinoma, Squamous Cell - virology
CD3 Complex - analysis
CD4 Antigens - analysis
CD4-Positive T-Lymphocytes - immunology
CD8 Antigens - analysis
CD8-Positive T-Lymphocytes - immunology
Clinical outcomes
Forkhead Transcription Factors - analysis
Human papillomavirus
Humans
Immunohistochemistry - methods
Lymphocyte Subsets - immunology
Lymphocytes, Tumor-Infiltrating - immunology
Muscle, Smooth - chemistry
Oropharyngeal Neoplasms - immunology
Oropharyngeal Neoplasms - mortality
Oropharyngeal Neoplasms - pathology
Oropharyngeal Neoplasms - radiotherapy
Oropharyngeal Neoplasms - virology
Oropharynx - immunology
Oropharynx - pathology
Papillomaviridae - isolation & purification
Prognosis
Translational Therapeutics
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Summary:Patients with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) have a better prognosis than those with HPV-negative tumours. There is interest in de-escalating their treatment but strategies are needed for risk stratification to identify subsets with a poor prognosis. This study investigated tumour-infiltrating lymphocytes (TILs) in relation to HPV tumour status and patient survival. Biopsies from 218 patients diagnosed with OPSCC between 2002 and 2011, who underwent chemo/radiotherapy were analysed for HPV by PCR, in-situ hybridisation and p16 immunohistochemistry (IHC). One hundred and thirty-nine samples with concordant HPV detection were analysed for CD3, CD4, CD8 and FoxP3 expression in tumour and stromal regions using multiplexIHC and multispectral image analysis. Labelling of smooth muscle actin (SMA) identified activated stroma. Human papillomavirus-positive compared with HPV-negative OPSCC had higher infiltration in both tumour and stromal areas of CD4 and CD8 T cells but not FoxP3 T regulatory cells. Only CD3+CD8+ stromal and not tumour area infiltration was associated with increased survival (P=0.02). There was significantly higher SMA expression in HPV-positive compared with -negative tumours, which did not correlate with survival. Studies of TILs for risk stratification in OPSCC should assess stromal infiltration.
ISSN:0007-0920
1532-1827
DOI:10.1038/bjc.2015.277