Neck Squamous Cell Carcinoma Survival Research Articles

Abstract A094: Association between head and neck squamous cell carcinoma survival, tobacco use, and alcohol use, 2010-2021

Abstract The number of survivors of head and neck squamous cell carcinoma (HNSCC) in the United States is expected to rise in coming years due to higher quality and more accessible cancer care, diminished smoking and alcohol consumption rates, and increased frequency of less aggressive human papillomavirus (HPV)-associated oropharyngeal cancers. In developed nations, about 80% of HNSCC patients are current smokers, recent quitters (within the past year), and former smokers. About 39% of HNSCC patients living in the United States say that they are current drinkers, drinkers who exceed moderate levels, and binge drinkers. Of all HNSCC cases, between 72% and 80% are associated with specifically tobacco use, alcohol use, or the two. Tobacco use and alcohol consumption have been shown to be predictive for HNSCC diagnosis and survival. However, the underlying trends and social determinants linking HNSCC survival to tobacco use and alcohol consumption are poorly understood. To reach a better understanding, data will be sourced from the National Health Interview Survey from 2010 to 2021, adjusted for age and other confounders, and then analyzed with Cox proportional hazards regression analysis. The results will inform a deeper understanding of the connections between HNSCC survival and tobacco and alcohol use and can point to new approaches and treatment targets for patient care. Citation Format: Rashad Rahman, Meng Chen, Nosayaba Osazuwa-Peters. Association between head and neck squamous cell carcinoma survival, tobacco use, and alcohol use, 2010-2021 [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A094.

Radiomics for therapy-specific head and neck squamous cell carcinoma survival prognostication (part I)

BackgroundTreatment plans for squamous cell carcinoma of the head and neck (SCCHN) are individually decided in tumor board meetings but some treatment decision-steps lack objective prognostic estimates. Our purpose was to explore the potential of radiomics for SCCHN therapy-specific survival prognostication and to increase the models’ interpretability by ranking the features based on their predictive importance.MethodsWe included 157 SCCHN patients (male, 119; female, 38; mean age, 64.39 ± 10.71 years) with baseline head and neck CT between 09/2014 and 08/2020 in this retrospective study. Patients were stratified according to their treatment. Using independent training and test datasets with cross-validation and 100 iterations, we identified, ranked and inter-correlated prognostic signatures using elastic net (EN) and random survival forest (RSF). We benchmarked the models against clinical parameters. Inter-reader variation was analyzed using intraclass-correlation coefficients (ICC).ResultsEN and RSF achieved top prognostication performances of AUC = 0.795 (95% CI 0.767–0.822) and AUC = 0.811 (95% CI 0.782–0.839). RSF prognostication slightly outperformed the EN for the complete (ΔAUC 0.035, p = 0.002) and radiochemotherapy (ΔAUC 0.092, p < 0.001) cohort. RSF was superior to most clinical benchmarking (p ≤ 0.006). The inter-reader correlation was moderate or high for all features classes (ICC ≥ 0.77 (± 0.19)). Shape features had the highest prognostic importance, followed by texture features.ConclusionsEN and RSF built on radiomics features may be used for survival prognostication. The prognostically leading features may vary between treatment subgroups. This warrants further validation to potentially aid clinical treatment decision making in the future.

Prediction of head and neck squamous cell carcinoma survival based on the expression of 15 lncRNAs.

Recent evidence suggests that long noncoding RNAs (lncRNAs) are essential regulators of many cancer-related processes, including cancer cell proliferation, invasion, and migration. There is thus a reason to believe that the detection of lncRNAs may be useful as a diagnostic and prognostic strategy for cancer detection, however, at present no effective genome-wide tests are available for clinical use, constraining the use of such a strategy. In this study, we performed a comprehensive assessment of lncRNAs expressed in samples in the head and neck squamous cell carcinoma (HNSCC) cohort available in The Cancer Genome Atlas database. A risk score (RS) model was constructed based on the expression data of these 15 lncRNAs in the validation data set of HNSCC patients and was subsequently validated in validation data set and the entire data set. We were able to stratify patients into high- and low-risk categories, using our lncRNA expression panel to determine an RS, with significant differences in overall survival (OS) between these two groups in our test set (median survival, 1.863 vs. 5.484 years; log-rank test, p < 0.001). We were able to confirm the predictive value of our 15-lncRNA signature using both a validation data set and a full data set, finding our signature to be reproducible and effective as a means of predicting HNSCC patient OS. Through the multivariate Cox regression and stratified analyses, we were further able to confirm that the predictive value of this RS was independent of other predictive factors such as clinicopathological parameters. The Gene set enrichment analysis revealed potential functional roles for these 15 lncRNAs in tumor progression. Our findings indicate that an RS established based on a panel of lncRNA expression signatures can effectively predict OS and facilitate patient stratification in HNSCC.

Association Between Head and Neck Squamous Cell Carcinoma Survival, Smoking at Diagnosis, and Marital Status

While the adverse association between smoking and head and neck squamous cell carcinoma (HNSCC) survival has been well described, there are also inconclusive studies and those that report no significant changes in HNSCC survival and overall mortality due to smoking. There is also a lack of studies investigating the association of marital status on smoking status at diagnosis for patients with HNSCC. To examine the association between patient smoking status at HNSCC diagnosis and survival and the association between marital status and smoking in these patients. This retrospective cohort study was conducted by querying the Saint Louis University Hospital Tumor Registry for adults with a diagnosis of HNSCC and treated at the university academic medical center between 1997 and 2012; 463 confirmed cases were analyzed. Cox proportional hazards regression analysis was used to evaluate association of survival with smoking status at diagnosis and covariates. A multivariate logistic regression model was used to assess whether marital status was associated with smoking at diagnosis adjusting for covariates. Of the 463 total patients (338 men, 125 women), 92 (19.9%) were aged 18 to 49 years; 233 (50.3%) were aged 50 to 65 years; and 138 (29.8%) were older than 65 years. Overall, 56.2% of patients were smokers at diagnosis (n = 260); 49.6% were married (n = 228); and the mortality rate was 54.9% (254 died). A majority of patients were white (81.0%; n = 375). Smokers at diagnosis were more likely to be younger (ie, <65 years), unmarried, and to drink alcohol. We found a statistically significant difference in median survival time between smokers (89 months; 95% CI, 65-123 months) and nonsmokers at diagnosis (208 months; 95% CI, 129-235 months). In the adjusted Cox proportional hazards model, patients who were smokers at diagnosis were almost twice as likely to die during the study period as nonsmokers (hazard ratio, 1.98; 95% CI, 1.42-2.77). In the multivariate logistic regression analysis, unmarried patients were 76% more likely to use tobacco than married patients (adjusted odds ratio, 1.76; 95% CI, 1.08-2.84). Smokers were almost twice as likely as nonsmokers to die during the study period. We also found that those who were married were less likely to be smokers at diagnosis. Our study suggests that individualized cancer care should incorporate social support and management of cancer risk behaviors.

A seven-gene prognostic signature for rapid determination of head and neck squamous cell carcinoma survival.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer and displays divergent clinical outcomes. Prognostic biomarkers might improve risk stratification and survival prediction. We aimed to investigate the prognostic genes associated with overall survival. A two-step gene selection method was used to develop a seven-gene-based prognostic model based on the training set collected from The Cancer Genome Atlas (TCGA). In addition, the prognostic model was validated in an independent testing set from Gene Expression Omnibus (GEO). The score based on the model successfully distinguished HNSCC survival into high-risk and low-risk groups in the training set (HR, 2.79; 95% CI, 1.98–3.92; P=4.05×10−9) and the testing set (HR, 2.05; 95% CI, 1.35–3.11; P=7.98×10−4). In addition, the score could significantly predict 5-year survival by ROC curves (AUCs for training set, 0.73; testing set, 0.66). Combining risk scores with clinical characteristics improved the AUCs beyond using clinical characteristics alone (training set, from 0.57 to 0.75; testing set, from 0.63 to 0.72). A subgroup sensitivity analysis with HPV status and tumor sites revealed that the risk score was significant in all subgroups except oral cavity tumors of the testing set. Furthermore, HPV-positive status improves survival in oropharyngeal HNSCC but not non-oropharyngeal HNSCC. In conclusion, the seven-gene prognostic signature is a reliable and practical prognostic tool for HNSCC. This approach can add prognostic value to clinical characteristics and provides a new possibility for individualized treatment.

Lewis x Antigen is Associated to Head and Neck Squamous Cell Carcinoma Survival.

Head and neck squamous cell carcinoma (HNSCC) is an aggressive disease with poor prognosis without appropriate prognostic markers. Previous research shows that Lewis antigens have been involved in carcinoma dissemination and patients´ survival. Fucosyl and sialyltransferases are the enzymes implicated in the Lewis antigens synthesis. The purpose of this study was to evaluate the prognostic utility of Lewis antigens in HNSCC. We conducted a prospective research including histological samples from 79 patients with primary HNSCC. Lewis x and sialyl Lewis x expression were detected by immunohistochemistry; patient's data, progression free, and overall survival were documented. A statistical correlation study of antigenic expression and patients´ histopathological variables was performed. Cox regression models with internal validation procedures were employed to analyze survival data. By immunohistochemistry, Lewis x was detected in 34/79 (43%) tumor samples, while sialyl Lewis x only in 11/79 (14%). Lewis x expression showed a positive correlation with tumor differentiation and a better overall survival for Lewis x+patients was detected. Moreover, multivariate Cox's regression analysis showed that Lewis x is an independent predictor of better overall survival. The in silico analysis supported the presence of deregulated fucosyl (FUT4) and sialyltransferase (ST3GAL4) in the Lewis synthetic pathway related to patient survival. These results suggest that Lewis x expression is associated with a better outcome in patients with HNSCC.

Gene expression analysis of head and neck squamous cell carcinoma survival and recurrence.

The squamous cell carcinomas represent about 90 % of all head and neck cancers, ranking the sixth most common human cancer. Approximately 450,000 of new cases of head and neck squamous cell carcinoma (HNSCC) are diagnosed every year. Unfortunately, because of diagnosis at the advanced stages and early metastasis to the lymph nodes, the HNSCC is associated with very high death rate. Identification of signature biomarkers and molecularly targeted therapies could provide more effective and specific cancer treatment, prevent recurrence, and increase survival rate. We used paired tumor and adjacent normal tissue samples to screen with RT² Profiler™ PCR Array Human Cancer PathwayFinderTM . Total of 20 up-regulated genes and two down-regulated genes were screened out. Out of 22 genes, 12 genes were subsequently validated to be significantly altered in the HNSCC; the samples were from all 41 patients. Five year survival and recurrence selected genes that could represent the biomarkers of survival and recurrence of the disease. We believe that comprehensive understanding of the unique genetic characteristics of HNSCC could provide novel diagnostic biomarkers and meet the requirement for molecular-targeted therapy for the HNSCC.

Human Papillomavirus-Associated Head and Neck Squamous Cell Carcinoma Survival: A Comparison by Tumor Site and Initial Treatment

Recent evidence suggests that human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) patients have better survival than HPV-negative patients. However, it is unclear if similar patterns for survival exist across different tumor sites, and whether HPV-associated prognosis is modified by type of treatment. We prospectively tested 222 histologically confirmed HNSCC primary tumors for HPV DNA by PCR and HPV E6/E7 RNA by RT-PCR prior to treatment at a large urban health center. Cox proportional hazard ratio models were constructed to assess HPV-associated differences in overall and disease-specific survival adjusting for clinical and demographic covariates. HPV detection varied significantly by primary HNSCC tumor site, from 35 % for oropharynx, to 25 % for hypopharynx, 5 % for larynx, and 3 % for oral cavity (p < 0.0001), with HPV16 accounting for the majority (95 %) of HPV-positive tumors. The hazard-risk of overall and disease-specific death comparing HPV16-positive versus negative oropharyngeal HNSCC was reduced by 74 and 89 %, respectively (p values < 0.05), and was independent of other prognostic indicators; no statistically significant changes in outcomes were observed for non-oropharyngeal HNSCC sites. Prediction of overall survival was better with combined DNA and RNA HPV16 positive PCR detection. There was no difference in HPV16-associated survival whether patients received either surgery or (chemo)radiotherapy as their initial treatment modality. Improved HPV-associated HNSCC survival is limited to patients with oropharyngeal primaries. No selective treatment advantage is observed for HPV-positive tumors, although clinical trials are needed to evaluate which treatment modalities provide the most benefit for HPV-positive HNSCC.

Inhibitor of differentiation 1 contributes to head and neck squamous cell carcinoma survival via the NF-kappaB/survivin and phosphoinositide 3-kinase/Akt signaling pathways.

A key issue in cancer is apoptosis resistance. However, little is known about the transcription factors that contribute to cellular survival of head and neck squamous cell carcinoma (HNSCC). Three batches (54, 64, and 38) of HNSCC specimens were used for cellular and molecular analyses to determine the major molecular signaling pathways for cellular survival in HNSCC. Animal models (cell culture and xenografts) were used to verify the importance of apoptosis resistance in HNSCC. Inhibitor of differentiation (Id) family member, Id1, was significantly upregulated in clinical HNSCC specimens and acted to protect keratinocytes from apoptosis. Transfection of HNSCC cells with Id1 in vitro induced the phosphorylation of Akt (p-Akt) via phosphoinositide 3-kinase and increased the expression of survivin via NF-kappaB. Blockage of both pathways by specific inhibitors (LY294002 and IkappaBalphaM, respectively) abrogated Id1-induced cell survival of keratinocytes. In vivo studies showed that increased expression of Id1 allowed nontumorigenic keratinocytes (Rhek-1A) to become tumorigenic in nude mice by increased expression of survival genes such as p-Akt and survivin. More importantly, short interfering RNA for Id1 significantly reduced HNSCC tumor volume of HNSCC in xenograft studies. Analysis of clinical data verified the importance of the Id1 downstream molecule, survivin, in the prognosis of HNSCC patients. The above data, taken together, suggest that Id1 and its downstream effectors are potential targets for treatment of HNSCC because of their contribution to apoptosis resistance.

A proposal of pathological classification (pTNM) of patients with head and neck cancer according to capsular rupture (pN- RC)

16525 Background: Lymph node metastasis remains one of the most significant prognostic factors of head and neck squamous cell carcinoma survival. Several studies have demonstrated that capsular rupture (CR) significantly decreases survival in patients with a positive neck dissection. We proposed to investigate whether inclusion of CR in the pTNM improves the prognostic capacity of the classification. Methods: We reviewed 841 patients (p) who underwent neck dissection and had a minimum follow-up of two years. The Kaplan-Meier method was used to analyce survival according to presence of neck nodes with CR and number of nodes with CR. Results: We analyzed 841p (151 oral cavity, 97 oropharynx, 136 hypopharynx, 258 supraglotis, 151 glotis and 48 only node; T1, 208 T2, 336 T3, 164 T4; 349 N0, 174 N1, 242 T2 and 78 N3). Treatment was surgery in 220 p and surgery plus radiotherapy in 621p. We treated 465 p with induction chemotherapy. Five-year survival was: 87% for pN0 (n=34), 67.2% for pN1RC-negative (n=118), 74.6% for pN1RC-positive (n=24), 51.7% for pN2RC-negative (n=127), 39.8% for pN2RC-positive only one node (n=58), 17.4% for pN2RC-positive more than one node (n=93) and 21.7% for pN3 (n=72). Conclusions: These results indicate that including CR information in the pTNM improves prognostic capacity of the classification. We propose four pTNM categories: Category 0: pN0; category 1: pN1RC-negative or -positive; category 2: pN2RC-negative or pN2RC-positive only one node; category 3: pN2RC-positive more than one node or pN3. No significant financial relationships to disclose.