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Human papillomavirus drives tumor development throughout the head and neck: improved prognosis is associated with an immune response largely restricted to the oropharynx

Human papillomavirus drives tumor development throughout the head and neck: improved prognosis is associated with an immune response largely restricted to the oropharynx
Human papillomavirus drives tumor development throughout the head and neck: improved prognosis is associated with an immune response largely restricted to the oropharynx
Purpose: In squamous cell carcinomas of the head and neck (HNSCC), the increasing incidence of oropharyngeal squamous cell carcinomas (OPSCCs) is attributable to human papillomavirus (HPV) infection. Despite commonly presenting at late stage, HPV-driven OPSCCs are associated with improved prognosis compared with HPV-negative disease. HPV DNA is also detectable in nonoropharyngeal (non-OPSCC), but its pathogenic role and clinical significance are unclear. The objectives of this study were to determine whether HPV plays a causal role in non-OPSCC and to investigate whether HPV confers a survival benefit in these tumors.

Methods: Meta-analysis was used to build a cross-tissue gene-expression signature for HPV-driven cancer. Classifiers trained by machine-learning approaches were used to predict the HPV status of 520 HNSCCs profiled by The Cancer Genome Atlas project. DNA methylation data were similarly used to classify 464 HNSCCs and these analyses were integrated with genomic, histopathology, and survival data to permit a comprehensive comparison of HPV transcript-positive OPSCC and non-OPSCC.

Results: HPV-driven tumors accounted for 4.1% of non-OPSCCs. Regardless of anatomic site, HPV+ HNSCCs shared highly similar gene expression and DNA methylation profiles; nonkeratinizing, basaloid histopathological features; and lack of TP53 or CDKN2A alterations. Improved overall survival, however, was largely restricted to HPV-driven OPSCCs, which were associated with increased levels of tumor-infiltrating lymphocytes compared with HPV-driven non-OPSCCs.

Conclusion: Our analysis identified a causal role for HPV in transcript-positive non-OPSCCs throughout the head and neck. Notably, however, HPV-driven non-OPSCCs display a distinct immune microenvironment and clinical behavior compared with HPV-driven OPSCCs.
1527-7755
1-12
Chakravarthy, Ankur
736774ce-5094-45d8-a148-aaa35466297e
Henderson, Stephen
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Thirdborough, Stephen M.
161784fb-c8e3-4beb-86b1-cd8bc8ddf8de
Ottensmeier, Christian H.
42b8a398-baac-4843-a3d6-056225675797
Su, Xiaoping
b067387d-d821-4d24-a98f-8f8670a25b68
Lechner, Matt
327faa2a-e083-46bb-8da6-337114f3a172
Feber, Andrew
cdc62c70-e4c3-4a70-8eff-515a6eaf895b
Thomas, Gareth J.
2ff54aa9-a766-416b-91ee-cf1c5be74106
Fenton, Tim R.
98dfc021-d0ba-4562-81a6-2baea646dd0b
Chakravarthy, Ankur
736774ce-5094-45d8-a148-aaa35466297e
Henderson, Stephen
ab5f1916-1731-4d07-9d92-4a34f6cbf88e
Thirdborough, Stephen M.
161784fb-c8e3-4beb-86b1-cd8bc8ddf8de
Ottensmeier, Christian H.
42b8a398-baac-4843-a3d6-056225675797
Su, Xiaoping
b067387d-d821-4d24-a98f-8f8670a25b68
Lechner, Matt
327faa2a-e083-46bb-8da6-337114f3a172
Feber, Andrew
cdc62c70-e4c3-4a70-8eff-515a6eaf895b
Thomas, Gareth J.
2ff54aa9-a766-416b-91ee-cf1c5be74106
Fenton, Tim R.
98dfc021-d0ba-4562-81a6-2baea646dd0b

Chakravarthy, Ankur, Henderson, Stephen, Thirdborough, Stephen M., Ottensmeier, Christian H., Su, Xiaoping, Lechner, Matt, Feber, Andrew, Thomas, Gareth J. and Fenton, Tim R. (2016) Human papillomavirus drives tumor development throughout the head and neck: improved prognosis is associated with an immune response largely restricted to the oropharynx. Journal of Clinical Oncology, 1-12. (doi:10.1200/JCO.2016.68.2955).

Record type: Article

Abstract

Purpose: In squamous cell carcinomas of the head and neck (HNSCC), the increasing incidence of oropharyngeal squamous cell carcinomas (OPSCCs) is attributable to human papillomavirus (HPV) infection. Despite commonly presenting at late stage, HPV-driven OPSCCs are associated with improved prognosis compared with HPV-negative disease. HPV DNA is also detectable in nonoropharyngeal (non-OPSCC), but its pathogenic role and clinical significance are unclear. The objectives of this study were to determine whether HPV plays a causal role in non-OPSCC and to investigate whether HPV confers a survival benefit in these tumors.

Methods: Meta-analysis was used to build a cross-tissue gene-expression signature for HPV-driven cancer. Classifiers trained by machine-learning approaches were used to predict the HPV status of 520 HNSCCs profiled by The Cancer Genome Atlas project. DNA methylation data were similarly used to classify 464 HNSCCs and these analyses were integrated with genomic, histopathology, and survival data to permit a comprehensive comparison of HPV transcript-positive OPSCC and non-OPSCC.

Results: HPV-driven tumors accounted for 4.1% of non-OPSCCs. Regardless of anatomic site, HPV+ HNSCCs shared highly similar gene expression and DNA methylation profiles; nonkeratinizing, basaloid histopathological features; and lack of TP53 or CDKN2A alterations. Improved overall survival, however, was largely restricted to HPV-driven OPSCCs, which were associated with increased levels of tumor-infiltrating lymphocytes compared with HPV-driven non-OPSCCs.

Conclusion: Our analysis identified a causal role for HPV in transcript-positive non-OPSCCs throughout the head and neck. Notably, however, HPV-driven non-OPSCCs display a distinct immune microenvironment and clinical behavior compared with HPV-driven OPSCCs.

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More information

Accepted/In Press date: 1 April 2016
e-pub ahead of print date: 31 October 2016
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 402822
URI: https://eprints.soton.ac.uk/id/eprint/402822
ISSN: 1527-7755
PURE UUID: 54eac9cc-9493-437b-b19c-4c8e3e0a4a6e

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Date deposited: 16 Nov 2016 14:04
Last modified: 01 Jun 2018 16:32

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Contributors

Author: Ankur Chakravarthy
Author: Stephen Henderson
Author: Xiaoping Su
Author: Matt Lechner
Author: Andrew Feber
Author: Tim R. Fenton

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