Dataset Information

Mechanisms of pain and their manifestations in head and neck cancer: Importance of classifying pain subtypes.

ABSTRACT:

Background

Pain is an under-recognized complaint among head and neck cancer (HNC) survivors. Treatment is hindered by inadequate characterization of pain.

Methods

A secondary analysis from a prospective, longitudinal study was conducted to characterize pain prevalence, quality, and functional consequences in 77 HNC patients. Pain and pain-related outcomes were captured before treatment, at end-of-treatment, and 3, 6, 9 and 12 months post-treatment.

Results

Pain was most prevalent at end-of-treatment and declined over time. Chronicity of pain was established by 6 months post-treatment. Oral mucosal neuropathic pain was the most common chronic pain subtype at 12 months post-treatment. Widespread joint and muscle pain was also present at lower numbers. 40.2% of patients continued to require analgesics at 12 months.

Conclusion

Peripheral and central pain subtypes contribute significantly to chronic pain in HNC survivors. Preventive and treatment regimens should be tailored to specific pain subtypes for optimal symptom control.

SUBMITTER: Lou DI

PROVIDER: S-EPMC9292513 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Mechanisms of pain and their manifestations in head and neck cancer: Importance of classifying pain subtypes.

Lou Dianne I DI Dietrich Mary S MS Deng Jie J Murphy Barbara A BA

Head & neck 20211007 12

<h4>Background</h4>Pain is an under-recognized complaint among head and neck cancer (HNC) survivors. Treatment is hindered by inadequate characterization of pain.<h4>Methods</h4>A secondary analysis from a prospective, longitudinal study was conducted to characterize pain prevalence, quality, and functional consequences in 77 HNC patients. Pain and pain-related outcomes were captured before treatment, at end-of-treatment, and 3, 6, 9 and 12 months post-treatment.<h4>Results</h4>Pain was most pre ...[more]

PMID: 34617646

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Project description:Head and neck cancer (HNC) affects over 890,000 people annually worldwide and has a mortality rate of 50%. Aside from poor survival, HNC pain impairs eating, drinking, and talking in patients, severely reducing quality of life. Different pain phenotype in patients (allodynia, hyperalgesia, and spontaneous pain) results from a combination of anatomical, histopathological, and molecular differences between cancers. Poor pathologic features (e.g., perineural invasion, lymph node metastasis) are associated with increased pain. The use of syngeneic/immunocompetent animal models, as well as a new mouse model of perineural invasion, provides novel insights into the pathobiology of HNC pain. Glial and immune modulation of the tumor microenvironment affect not only cancer progression but also pain signaling. For example, Schwann cells promote cancer cell proliferation, migration, and secretion of nociceptive mediators, whereas neutrophils are implicated in sex differences in pain in animal models of HNC. Emerging evidence supports the existence of a functional loop of cross-activation between the tumor microenvironment and peripheral nerves, mediated by a molecular exchange of bioactive contents (pronociceptive and protumorigenic) via paracrine and autocrine signaling. Brain-derived neurotrophic factor, tumor necrosis factor α, legumain, cathepsin S, and A disintegrin and metalloprotease 17 expressed in the HNC microenvironment have recently been shown to promote HNC pain, further highlighting the importance of proinflammatory cytokines, neurotrophic factors, and proteases in mediating HNC-associated pain. Pronociceptive mediators, together with nerve injury, cause nociceptor hypersensitivity. Oncogenic, pronociceptive mediators packaged in cancer cell-derived exosomes also induce nociception in mice. In addition to increased production of pronociceptive mediators, HNC is accompanied by a dampened endogenous antinociception system (e.g., downregulation of resolvins and µ-opioid receptor expression). Resolvin treatment or gene delivery of µ-opioid receptors provides pain relief in preclinical HNC models. Collectively, recent studies suggest that pain and HNC progression share converging mechanisms that can be targeted for cancer treatment and pain management.

Project description:Head and neck squamous cell carcinoma (HNSC) exhibits genetic heterogeneity in etiologies, tumor sites, and biological processes, which significantly impact therapeutic strategies and prognosis. While the influence of human papillomavirus on clinical outcomes is established, the molecular subtypes determining additional treatment options for HNSC remain unclear and inconsistent. This study aims to identify distinct HNSC molecular subtypes to enhance diagnosis and prognosis accuracy. In this study, we collected three HNSC microarrays (n = 306) from the Gene Expression Omnibus (GEO), and HNSC RNA-Seq data (n = 566) from The Cancer Genome Atlas (TCGA) to identify differentially expressed genes (DEGs) and validate our results. Two scoring methods, representative score (RS) and perturbative score (PS), were developed for DEGs to summarize their possible activation functions and influence in tumorigenesis. Based on the RS and PS scoring, we selected candidate genes to cluster TCGA samples for the identification of molecular subtypes in HNSC. We have identified 289 up-regulated DEGs and selected 88 genes (called HNSC88) using the RS and PS scoring methods. Based on HNSC88 and TCGA samples, we determined three HNSC subtypes, including one HPV-associated subtype, and two HPV-negative subtypes. One of the HPV-negative subtypes showed a relationship to smoking behavior, while the other exhibited high expression in tumor immune response. The Kaplan-Meier method was used to compare overall survival among the three subtypes. The HPV-associated subtype showed a better prognosis compared to the other two HPV-negative subtypes (log rank, p = 0.0092 and 0.0001; hazard ratio, 1.36 and 1.39). Additionally, within the HPV-negative group, the smoking-related subgroup exhibited worse prognosis compared to the subgroup with high expression in immune response (log rank, p = 0.039; hazard ratio, 1.53). The HNSC88 not only enables the identification of HPV-associated subtypes, but also proposes two potential HPV-negative subtypes with distinct prognoses and molecular signatures. This study provides valuable strategies for summarizing the roles and influences of genes in tumorigenesis for identifying molecular signatures and subtypes of HNSC.

Dataset Information

Mechanisms of pain and their manifestations in head and neck cancer: Importance of classifying pain subtypes.

Background

Methods

Results

Conclusion

Publications

Mechanisms of pain and their manifestations in head and neck cancer: Importance of classifying pain subtypes.

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