IGSF4 methylation as an independent marker of human papillomavirus-positive oropharyngeal squamous cell carcinoma.
JAMA Otolaryngol Head Neck Surg
; 141(3): 257-63, 2015 Mar.
Article
em En
| MEDLINE
| ID: mdl-25569158
ABSTRACT
IMPORTANCE Human papillomavirus (HPV) is a known causative agent for oropharyngeal squamous cell carcinoma (OPSCC). Whereas it is becoming more firmly established that HPV-positive head and neck squamous cell carcinoma is associated with better survival outcomes, believed to be because of better response to chemoradiation therapy, the specific mechanisms for these improved survival outcomes remain underexplored. OBJECTIVE:
To examine the relationship between HPV status and promoter methylation in an OPSCC cohort. DESIGN, SETTING, ANDPARTICIPANTS:
Real-time quantitative polymerase chain reaction was used to examine oncogenic HPV type 16 in a retrospective cohort of 121 patients with primary OPSCC. Aberrant promoter methylation of IGSF4, DAPK1, and ESR1 genes, known to be methylated in head and neck squamous cell carcinoma, including OPSCC, was examined by means of quantitative methylation-specific polymerase chain reaction.INTERVENTIONS:
Patients received standard therapy. MAIN OUTCOMES ANDMEASURES:
Univariate associations between HPV and methylation were analyzed using Fisher exact tests followed by multivariable logistic regression. Cox proportional-hazards regression was used to model the risk of death given age, race, sex, HPV status, methylation, stage, smoking, and treatment.RESULTS:
In univariate logistic regression analyses, HPV-positive status was significantly associated with Caucasian race (P = .02), treatment (radiotherapy only, P = .01; chemoradiotherapy, P = .007), and IGSF4 methylation (P = .005). The final multivariate logistic model, after controlling for patient characteristics (sex, age, smoking, race, and treatment) with backward variable selection among genes, retained IGSF4 methylation (OR, 4.5 [95% CI, 1.6-12.8]; P = .005), Caucasian race (OR, 2.9 [95% CI, 1.0-8.3]; P = .053), treatment (radiotherapy only vs neither OR, 11.62 [95% CI, 2.02-66.82]; P = .02; chemoradiotherapy vs neither OR, 11.15 [95% CI, 1.92-64.65]; P = .01), male sex (OR, 4.7 [95% CI, 1.3-17.0]; P = .02), and younger age (OR, 0.9 [95% CI, 0.90-1.0]; P = .008) as independent predictors of HPV-positive status. Cox regression modeling indicated HPV-negative status, age, male sex, smoking, and radiation treatment as independent predictors of mortality. CONCLUSIONS AND RELEVANCE Methylation of IGSF4 is an independent predictor of HPV-positive status. DNA methylation in conjunction with HPV infection appears to play a role in OPSCC.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Imunoglobulinas
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Carcinoma de Células Escamosas
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Neoplasias Orofaríngeas
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Moléculas de Adesão Celular
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Metilação de DNA
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Papillomavirus Humano 16
Tipo de estudo:
Diagnostic_studies
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Etiology_studies
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Incidence_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article