DNA methylation of indoleamine 2,3-dioxygenase 1 (IDO1) in head and neck squamous cell carcinomas correlates with IDO1 expression, HPV status, patients’ survival, immune cell infiltrates, mutational load, and interferon γ signature

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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Utilization of P16 in Head and Neck Cytology and Surgical Specimens After the Release of CAP Guidelines

American Journal of Clinical Pathology ◽

10.1093/ajcp/aqaa161.040 ◽

2020 ◽

Vol 154 (Supplement_1) ◽

pp. S22-S22

Author(s):

H Laharwani ◽

V Manucha ◽

G Jefferson ◽

L Jackson

Keyword(s):

Head And Neck ◽

Squamous Cell ◽

Squamous Cell Carcinomas ◽

Common Reason ◽

Unknown Primary ◽

Hpv Testing ◽

Neck Masses ◽

P16 Immunohistochemistry ◽

Hpv Status ◽

Wrong Site

Abstract Introduction/Objective HPV-positive oropharyngeal squamous cell carcinoma is biologically and clinically unique and has a survival advantage over other head and neck squamous cell carcinomas. In December 2017 College of American Pathologist published guidelines for testing HPV status in head and neck cancer. It was recommended that pathologists perform HR-HPV testing on head and neck squamous cell carcinomas from all patients with known oropharyngeal SCC not previously tested for HR-HPV, with suspected oropharyngeal SCC, or with metastatic SCC of unknown primary. The aim of this study was to determine the compliance of pathologists following the CAP guidelines. Methods Cases that underwent HPV testing using p16 immunohistochemistry for the years 2017 and 2019 were retrieved. Based on the guidelines, p16 testing was designated as “indicated” or “not indicated”. Results There were 196 cases in which p16 testing was performed in a period of 3 consecutive years. Of these, 175 were FNA/ biopsies and 21 were surgical resections. In 69 cases (56 FNAs and 13 biopsies) the biopsy was performed on neck masses with unknown primary. The compliance for p16 testing in OPC and Lymph nodes with metastatic SCC of unknown primary was 100%. In 34 (17.3%) cases p16 testing was not indicated, the most common reason being wrong site (85%) including the larynx, oral tongue, the floor of the mouth, buccal mucosa, and nasal mass. Of the unindicated p16s, 20 (58%) were received in consultation for continuity of care. Conclusion Not being clear about the site of the tumor is the most common reason for unindicated p16 testing. A clear designation of biopsy site and proper communication between pathologist and surgeon can improve utilization of p16 testing in head and neck carcinomas.

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Abstract 2642: Dietary intake is associated with tumor suppressor DNA methylation in head and neck squamous cell carcinomas

10.1158/1538-7445.am2012-2642 ◽

2012 ◽

Author(s):

Anna E. Arthur ◽

Justin A. Colacino ◽

Sonia A. Duffy ◽

Dana C. Dolinoy ◽

Jeffrey E. Terrell ◽

...

Keyword(s):

Dna Methylation ◽

Tumor Suppressor ◽

Dietary Intake ◽

Head And Neck ◽

Squamous Cell ◽

Squamous Cell Carcinomas

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Unique DNA Methylation Loci Distinguish Anatomic Site and HPV Status in Head and Neck Squamous Cell Carcinoma

Clinical Cancer Research ◽

10.1158/1078-0432.ccr-12-3280 ◽

2013 ◽

Vol 19 (19) ◽

pp. 5444-5455 ◽

Cited By ~ 56

Author(s):

Roberto A. Lleras ◽

Richard V. Smith ◽

Leslie R. Adrien ◽

Nicolas F. Schlecht ◽

Robert D. Burk ◽

...

Keyword(s):

Dna Methylation ◽

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Neck Squamous Cell Carcinoma ◽

Anatomic Site ◽

Hpv Status

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The landscape of CD28, CD80, CD86, CTLA4, and ICOS DNA methylation in head and neck squamous cell carcinomas

Epigenetics ◽

10.1080/15592294.2020.1754675 ◽

2020 ◽

Vol 15 (11) ◽

pp. 1195-1212 ◽

Cited By ~ 5

Author(s):

Luka de Vos ◽

Ingela Grünwald ◽

Emma Grace Bawden ◽

Jörn Dietrich ◽

Kathrin Scheckenbach ◽

...

Keyword(s):

Dna Methylation ◽

Head And Neck ◽

Squamous Cell ◽

Squamous Cell Carcinomas

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DNA Methylation Leaves Its Mark in Head and Neck Squamous Cell Carcinomas (HNSCC)

Current Genomics ◽

10.2174/1389202043348940 ◽

2004 ◽

Vol 5 (6) ◽

pp. 489-498 ◽

Cited By ~ 1

Author(s):

L. Smith ◽

C. Plass

Keyword(s):

Dna Methylation ◽

Head And Neck ◽

Squamous Cell ◽

Squamous Cell Carcinomas

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Peripheral Cytokine Levels Differ by HPV Status and Change Treatment-Dependently in Patients with Head and Neck Squamous Cell Carcinoma

International Journal of Molecular Sciences ◽

10.3390/ijms21175990 ◽

2020 ◽

Vol 21 (17) ◽

pp. 5990

Author(s):

Daphne Mytilineos ◽

Jasmin Ezić ◽

Adrian von Witzleben ◽

Joannis Mytilineos ◽

Ramin Lotfi ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Inflammatory Cytokines ◽

Squamous Cell ◽

Immune Cell ◽

Neck Squamous Cell Carcinoma ◽

Immune Mediators ◽

Radio Therapy ◽

Hpv Status

Cytokines and immune mediators play an important role in the communication between immune cells guiding their response to infectious diseases or cancer. In this study, a comprehensive longitudinal analysis of serum cytokines and immune mediators in head and neck squamous cell carcinoma (HNSCC) patients was performed. In a prospective, non-interventional, longitudinal study, blood samples from 22 HNSCC patients were taken at defined time points (TP) before, during, and every 3 months after completion of (chemo)radio)therapy (CRT/RT) until 12 months after treatment. Serum concentrations of 17 cytokines/immune mediators and High-Mobility-Group-Protein B1 (HMGB1) were measured by fluorescent bead array and ELISA. Concentrations of sFas were significantly elevated during and after CRT/RT, whereas perforin levels were significantly decreased after CRT/RT. Levels of MIP-1β and Granzyme B differed significantly during CRT/RT by HPV status. Increased HMGB1 levels were observed at recurrence, accompanied by high levels of IL-4 and IL-10. The sFas increase and simultaneous perforin decrease may indicate an impaired immune cell function during adjuvant radiotherapy. Increased levels of pro-inflammatory cytokines in HPV+ compared to HPV− patients seem to reflect the elevated immunogenicity of HPV-positive tumors. High levels of HMGB1 and anti-inflammatory cytokines at recurrence may be interpreted as a sign of immune evasion.

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