Dataset Information

Impact on survival of tobacco smoking for cases with oropharyngeal squamous cell carcinoma and known human papillomavirus and p16-status: a multicenter retrospective study.

ABSTRACT:

Background

Human papilloma virus (HPV) and tobacco smoking are important risk factors for development of oropharyngeal squamous cell carcinoma (OPSCC).

Aims/objectives

To evaluate the impact of tobacco smoking on survival for cases with OPSCC with known HPV- and p16INK4A(p16)-status.

Materials and methods

OPSCC cases at the University Hospital of Copenhagen, Rigshospitalet, Denmark (2000-2014) and at University Hospital of Giessen, Germany (2000-2009) were included. Survival was illustrated with Kaplan-Meier plots. The effect of smoking exposure on survival was evaluated by Cox-regression models. HPV-positivity was defined as positivity for both HPV-DNA and p16.

Results

We included 1316 OPSCC cases from 2000-2014 (48% HPV-positive). Smokers had a poorer outcome compared to non-smokers. Considering continuous smoking exposure, adding 10 pack-years of smoking increased hazard ratios irrespective of HPV-status.We observed a tendency to a greater impact on survival for cases with HPV-neg. tumours compared to cases with HPV-pos. tumours at low numbers of pack-years, yet the survival was similar at high numbers of pack-years. There was no significant difference in the impact of HPV-status on survival for non-smokers, however a highly significant difference for smokers.

Conclusions and significance

Smoking-status and number of pack-years at time of diagnosis impact survival for cases with OPSCC independent of HPV-status.

SUBMITTER: Gronhoj C

PROVIDER: S-EPMC6659794 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Publications

Impact on survival of tobacco smoking for cases with oropharyngeal squamous cell carcinoma and known human papillomavirus and p16-status: a multicenter retrospective study.

Grønhøj Christian C Jensen Jakob Schmidt JS Wagner Steffen S Dehlendorff Christian C Friborg Jeppe J Andersen Elo E Wittekindt Claus C Würdemann Nora N Sharma Shachi Jenny SJ Gattenlöhner Stefan S Klussmann Jens Peter JP von Buchwald Christian C

Oncotarget 20190723 45

<h4>Background</h4>Human papilloma virus (HPV) and tobacco smoking are important risk factors for development of oropharyngeal squamous cell carcinoma (OPSCC).<h4>Aims/objectives</h4>To evaluate the impact of tobacco smoking on survival for cases with OPSCC with known HPV- and p16INK4A(p16)-status.<h4>Materials and methods</h4>OPSCC cases at the University Hospital of Copenhagen, Rigshospitalet, Denmark (2000-2014) and at University Hospital of Giessen, Germany (2000-2009) were included. Surviva ...[more]

PMID: 31384393

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Project description:Importance:Clinical trials that deintensify treatment for patients with suspected human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) use p16 expression to identify HPV-mediated tumors and guide treatment. While p16 staining has a strong correlation with good outcomes, approximately 12% of p16-positive patients have recurrent disease. Biomarkers that reveal tumor-specific characteristics, such as nodal involvement, may change therapy decisions. Objective:To assess whether if a tumor-specific genetic signature exists for node-negative vs node-positive HPV 16-positive/p16-positive OPSCCs. Design, Setting, and Participants:This was a retrospective cohort study with randomized case selection for p16 OPSCCs undertaken at a university-based, tertiary care cancer center. Samples were collected from patients with p16-positive OPSCC. A total of 21 HPV 16/p16-positive tumors were used in this study. Main Outcomes and Measures:Gene expression profiles of node-negative vs node-positive tumor samples were evaluated using a differential expression analysis approach and the sensitivity and specificity of a molecular signature was determined. Results:Among the 21 patients in the study (3 women, 18 men; mean [SD] age, 54.6 [9.6] years), 6 had node-negative disease and 15 had node-positive disease. Using differential expression analysis, we found 146 genes that were significantly different in patients with node-negative disease vs those with node-positive disease, of which 15 genes were used to create a genetic signature that could distinguish node-negative-like from node-positive-like disease. The resultant molecular signature has a sensitivity of 88.2% (95% CI, 63.6%-98.5%) and specificity of 85.7% (95% CI, 42.1%-99.6%). The positive likelihood ratio of this signature was 6.1 (95% CI, 1.0-38.2) and the negative likelihood ratio was 0.1 (95% CI, 0.04-0.5). Given this population's prevalence of node-positive disease of 70.8%, the positive- and negative-predicative values for this gene signature were 93.7% (95% CI, 70.8%-98.9%) and 75.0% (95% CI, 44.1%-92.0%), respectively. In addition, we developed a gene signature using agnostic, machine learning software that identified a 40-gene profile that predicts node-negative disease from node-positive disease (area under the curve, 0.93; 95% CI, 0.63-1.00). Conclusions and Relevance:Many HPV-16 and p16-positive tumors are treated as "lower-risk," but they do not have similar genetic compositions at the biological level. The identification of subgroups with unique expression patterns, such as those with nodal metastases, may guide physicians toward alternative or more aggressive therapies. In our study, unguided clustering suggested that that the larger biological characteristics of a tumor could be a better prognostic biomarker.

Project description:Background and purposeHuman papillomavirus-associated oropharyngeal squamous cell carcinoma is increasing in prevalence and typically occurs in younger patients than human papillomavirus-negative squamous cell carcinoma. While imaging features of human papillomavirus-positive versus human papillomavirus-negative squamous cell carcinoma nodal metastases have been described, characteristics distinguishing human papillomavirus-positive from human papillomavirus-negative primary squamous cell carcinomas have not been well established. The purpose of this project was to evaluate the use of texture features to distinguish human papillomavirus-positive and human papillomavirus-negative primary oropharyngeal squamous cell carcinoma.Materials and methodsFollowing institutional review board approval, 40 patients with primary oropharyngeal squamous cell carcinoma and known human papillomavirus status who underwent contrast-enhanced CT between December 2009 and October 2013 were included in this study. Segmentation of the primary lesion was manually performed with a semiautomated graphical-user interface. Following segmentation, an in-house-developed texture analysis program extracted 42 texture features from each segmented volume. A t test was used to evaluate differences in texture parameters between human papillomavirus-positive and human papillomavirus-negative squamous cell carcinomas.ResultsOf the 40 included patients, 29 had human papillomavirus-positive oropharyngeal squamous cell carcinoma and 11 had human papillomavirus-negative oropharyngeal squamous cell carcinoma. Significant differences were seen in the histogram parameters median (P = .006) and entropy (P = .016) and squamous cell carcinoma entropy (P = .043).ConclusionsThere are statistically significant differences in some texture features between human papillomavirus-positive and human papillomavirus-negative oropharyngeal tumors. Texture analysis may be considered an adjunct to the evaluation of human papillomavirus status and characterization of squamous cell carcinoma.

Dataset Information

Impact on survival of tobacco smoking for cases with oropharyngeal squamous cell carcinoma and known human papillomavirus and p16-status: a multicenter retrospective study.

Background

Aims/objectives

Materials and methods

Results

Conclusions and significance

Publications

Impact on survival of tobacco smoking for cases with oropharyngeal squamous cell carcinoma and known human papillomavirus and p16-status: a multicenter retrospective study.

Similar Datasets

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