Negative Oropharyngeal Carcinoma Research Articles

1676: Unexpected correlation between DWI and treatment response in HPV negative oropharyngeal carcinoma

1676: Unexpected correlation between DWI and treatment response in HPV negative oropharyngeal carcinoma

Clinical characteristics and efficacy of oropharyngeal carcinoma with secondary primary tumor

Objective:To analysis the clinical features and prognosis in oropharyngeal carcinoma with secondary primary tumor. Methods:A retrospective analysis was performed on 468 pathologically confirmed oropharyngeal cancer as the primary tumor patients with p16 status, excluded distant metastasis, and admitted to the Chinese Academy of Medical Sciences from January 2010 to December 2020. The clinical features and prognosis of the secondary primary tumor were analyzed. Results:Among 468 patients with oropharyngeal cancer treated at initial diagnosed, 222 cases were P16-negative. With a median follow-up time of 64.3 months, 66 cases developed second primary cancer, with an incidence of 29.3%, among which 63.6%（42/66） were synchronous and 36.4%（24/66） were heterochronous, esophagus was the most commonly involved site. The 5-year OS of p16-negative oropharyngeal carcinoma with synchronous second primary cancer, without second primary cancer and with heterogeneous second primary cancer were 26.3% and 57.3% and 73.2%（P=0.001）; The second primary cancer accounted for 11.2%（12/107） of the deaths in the whole group, among them, the heterochronous second primary accounted for 75.0%（9/12）. There were 246 patients with p16 positive, with a median follow-up time of 52.4 months, 20 patients developed second primary cancer（8.1%）. Among them, 65.0%（13/20） were synchronous and 35.0%（7/20） were heterochronous. Esophagus was the most commonly involved site. The 4-year OS of p16-positive with synchronous, heterochronous and non-second primary cancer group were 51.9%, 80.7% and 83.3%. Secondary primary cancer accounted for 3.8%（2/52） of all deaths in p16 positvie group. Conclusion:The incidence of second primary cancer of p16 positive and negative oropharyngeal carcinoma were different. The esophagus was the most commonly involved site regardless of p16 status. Regardless of p16 status, the survival of patients with synchronous second primary cancer was worse than those without second primary cancer. For p16-negative oropharyngeal carcinoma, the prognosis was better in patients with heterogeneous second primary cancer, the second primary cancer is one of the main causes of death.

Differences in Survival Outcomes among Racial Minorities with Head and Neck Cancer

<h3>Purpose/Objective(s)</h3> While disparities in patient outcomes for head and neck squamous cell carcinoma (HNSCC) have been documented, the specific drivers of inferior outcomes among racial/ethnic (R/E) minorities remain poorly understood. Our objective was to identify the defining prognostic factors for survival outcomes among R/E minority HNSCC patients in the United States. <h3>Materials/Methods</h3> We identified HNSCC patients of all the major mucosal head and neck subsites treated with surgery, radiation, chemotherapy or a combination of modalities between 2004-2016 using the National Cancer Database (NCDB). Patient outcomes were stratified by R/E groups including White, Black, Hispanic, Native American/Other, and Asian. Covariates analyzed include ethnicity, race, insurance type, income, age, sex, stage, cancer site, co-morbidity status, treatment modality, and HPV status. Kaplan Meier analysis and log-rank test were used to estimate overall survival (OS) outcomes between strata. Cox proportional hazard regression models were used to assess the association between co-variates and risk of death. <h3>Results</h3> 311,032 HNSCC patients were treated between 2004-2016, of which 269,166 (86.5%) were White, 32,871 (10.5%) were Black, 6,285 (2%) were Asian, and 2,710 (0.8%) were Native American. By ethnicity, 12,379 (4%) were Hispanic. Compared to White HNSCC patients, Black patients were more likely to have Medicaid insurance (22% vs 8%, p<0.001), lower income (<30,000, 42% vs 13%, p<0.0001), Stage IV disease (39% vs 29%, p<0.0001), less likely to be treated with surgery (26% vs 15%, p<0.0001), and had a higher proportion of HPV negative oropharyngeal carcinoma (18% vs 21%, p<0.0001). Among patients treated with surgery, Black patients had a longer time to initiation of adjuvant RT compared to White patients (mean 58 vs 53 days, p<0.0001). Among all patients, 5-year OS for White, Black, Hispanic, Native American/Other, and Asian was 50.8%, 38.5%, 51.5%, 51.2%, and 57.2%, respectively (log rank, p<0.0001). Black patients had an inferior 5-year OS for the majority of HNSCC subsites, including the oral cavity, hypopharynx, larynx, nasal cavity, and oropharynx (all log-rank p<0.0001). Even among favorable HPV positive oropharynx cancer patients, Black patients had a significantly inferior OS compared to White patients (log-rank, p<0.0001). On multivariable analysis, Black patients had a higher mortality (HR:1.09, 95% CI, 1.02-1.155, P=0.003) after adjusting for income, insurance type, co-morbidity status, treatment modality, clinical stage, and HPV status. <h3>Conclusion</h3> This large cohort of HNSCC patients demonstrates that Black race is independently associated with worse OS. Efforts should be made to reduce clinical and non-clinical factors in racial minorities to further narrow the survival gaps in HNSCC. Further work is needed to better understand the biological basis for the worse outcomes seen after accounting for social determinants of health.

Current Perspective on HPV-Associated Oropharyngeal Carcinomas and the Role of p16 as a Surrogate Marker of High-Risk HPV

The incidence of oropharyngeal carcinomas associated with human papillomavirus (HPV) is continuously increasing. HPV-positive and -negative oropharyngeal carcinomas have different epidemiological, clinical, and molecular features, with HPV-positive tumors having a better response to treatment and better prognosis. An adequate staging system for HPV-related oropharyngeal carcinomas is needed, as the American Joint Committee on Cancer 7th Edition did not consider their unique biological behavior. At present, oropharyngeal carcinomas are subdivided into p16 positive and p16 negative tumors, based on their expression of p16, a surrogate marker of high-risk HPV. This review summarizes current knowledge of HPV-associated oropharyngeal carcinomas with emphasis on their molecular features and histopathology, as well as summarizes and compares HPV detection methods and genotyping techniques. This review also describes the prognostic significance of p16 expression in these tumors and significant changes in the staging of oropharyngeal carcinomas based on p16 expression, together with the justifications for these changes. Finally, this review reports the recommendations of the College of American Pathologists for testing HPV in head and neck cancers, supported by the American Society of Clinical Oncology. This work was supported by the Ministry of Health of the Czech Republic, grant No. 15-31627A. All rights reserved. Auto&#345;i deklarují, &#382;e v souvislosti s p&#345;edm&#283;tem studie nemají &#382;ádné komer&#269;ní zájmy. Redak&#269;ní rada potvrzuje, &#382;e rukopis práce splnil ICMJE kritéria pro publikace zasílané do biomedicínských &#269;asopis&#367;. Submitted: 18. 2. 2019 Accepted: 30. 5. 2019.

EP-2026 Diffusion weighted textural differences between p16 positive and negative oropharyngeal carcinoma

EP-2026 Diffusion weighted textural differences between p16 positive and negative oropharyngeal carcinoma

The IL-1/IL-1R axis induces greater fibroblast-derived chemokine release in human papillomavirus-negative compared to positive oropharyngeal cancer.

Human papillomavirus (HPV) is now recognised as a major aetiological agent in the pathogenesis of oropharyngeal carcinoma (OPC). HPV‐positive tumours are associated with better outcomes compared to HPV‐negative tumours, possibly due to differences in their aetiology and/or the tumour microenvironment. Increased numbers of tumour‐associated leukocytes have been observed in many cancers including OPC, with variable influence on prognosis depending on the leukocyte subpopulation investigated. Whether HPV status influences leukocyte recruitment to OPC remains unknown. This in‐vitro study examined differences in the chemoattractant capacity of HPV‐positive and HPV‐negative OPC cell lines. Gene and protein expression analysis demonstrated that whilst both monocultures of HPV‐positive and HPV‐negative cell lines, along with normal tonsillar fibroblasts (NTF), expressed low chemokine levels, NTF cultured with conditioned medium from HPV‐negative OPC cells expressed significantly higher levels of all chemokines tested compared to NTF incubated with the medium from HPV‐positive OPC cell lines. HPV‐negative OPC lines expressed IL‐1β mRNA whereas HPV‐positive cells did not, and NTF constitutively expressed IL‐1R1. Pre‐treatment with the IL‐R antagonist, anakinra or siRNA to IL‐1R1 significantly reduced chemokine secretion from NTF stimulated with conditioned medium from HPV‐negative tumour cells or recombinant IL‐1β (p < 0.05). These data suggest that secretion of chemokines is driven by the interaction between HPV‐negative OPC cells and stromal fibroblasts through an IL‐1/IL‐1R‐mediated mechanism that is less prominent within the HPV‐positive tumour microenvironment. These observations may explain differences in leukocyte sub‐populations recruited to HPV‐positive versus negative OPC and indicate that HPV status is a key determinant in controlling the inflammatory tumour microenvironment.

An NCDB Analysis Investigating Outcomes in HPV Negative Oropharyngeal Carcinoma - An Attempt to Bridge the Gap Due to Lack of Accrual in RTOG 1221

Transoral robotic surgery (TORS) represents a considerable technological advance in surgical technique in head and neck squamous cell carcinoma (HNSCC). RTOG 1221 was a proposed study of intensified local therapy for T1-2, N0-2b, HPV negative HNSCC of the oropharynx with TORS; this study closed after 15 months due to zero patient accrual1. In place of the prospective trial, the National Cancer Database (NCDB) can be utilized to follow survival outcomes in this patient population. Retrospective review was performed of the National Cancer Data Base 2004 – 2015 data for T1-2, N0-2b, oropharynx HNSCC. Patients were included for analysis if they were treated according to the regimens of RTOG1221 with TORS +/- adjuvant therapy, or chemoRT alone. Adjuvant treated must have been started within 3 months of TORS. Kaplan Meier overall survival (OS) estimates and log rank analysis was performed. A total of 1698 T1-2, N0-2b patients with HPV negative oropharyngeal HNSCC were analyzed. Median survival was not reached in either cohort. 126 patients had TORS +/- adjuvant therapy, with a median follow-up of 36.55 months (SD 17.53 months). This cohort had a 2-year survival estimate of 88.2% with standard error of 0.03. 1572 patients had chemoRT alone, with a median follow-up of 33.15 months (SD 18.33 months). This cohort had a 2-year survival estimate of 84.1% with standard error of 0.009. Log rank analysis of these groups demonstrates no statistically significant difference in OS, with a chi-square of 1.754 and a p-value of 0.185. OS outcomes of HPV negative patients treated with TORS +/- adjuvant therapy were not statistically significantly different than those treated with concurrent chemoRT alone. This NCDB data may offer insight into the role of TORS in treatment escalation for HPV negative oropharyngeal HNSCC, especially as this data matures over the next several years.

A 5‑year update of patients with HPV positive versus negative oropharyngeal cancer after radiochemotherapy in Austria.

SummaryBackgroundAfter publishing promising results for the treatment of patients with human papilloma virus (HPV) positive oropharyngeal cancer with radiochemotherapy regarding 2‑year survival, we present an update of the disease-specific and disease-free survival after 5 years.Patients and methodsA total of 29 patients of which 18 were HPV negative and 11 HPV positive with squamous cell carcinoma of the oropharynx received radiation therapy with or without chemotherapy (cisplatin) or immunotherapy (cetuximab) between 2007 and 2009. At time of the present analysis, six patients are still alive including four with HPV positive and two with HPV negative oropharyngeal carcinoma, while 15 out of 16 patients with HPV negative tumors died and 1 died of another cause with evidence of disease.ResultsSince the 2‑year disease-specific survival of patients with HPV positive cancer of the oropharynx was published with 100% versus 30.4% in HPV negative tumors, we now present the 5‑year disease-specific survival after treatment, which was 85.7% in HPV positive versus 11.1% in HPV negative patients.ConclusionWe present the results of patients receiving radiochemo(immuno)therapy for oropharyngeal cancer regarding the HPV status, which is still promising.

P16 status and interval neck dissection findings after a ‘clinically complete response’ to chemoradiotherapy in oropharyngeal squamous cell carcinoma

To evaluate the histopathological findings from post-treatment neck dissection of p16 positive and negative oropharyngeal carcinoma cases, after completion of chemoradiotherapy, and to question the role of neck dissection after a 'clinically complete response' to chemoradiotherapy. Data were collected retrospectively from a cohort of patients treated with curative intent using chemoradiotherapy and post-treatment neck dissection. Primary tumours underwent p16 immunohistochemistry. Neck dissection specimens were examined for viable cancer cells. A total of 76 cases were assessed. Viable cancer cells were detected from neck dissection in 29 per cent of p16 negative cases. Locoregional recurrence occurred in 12.9 per cent of p16 negative cases. The association between p16 positivity in the primary tumour and histopathologically negative neck dissection was significant (p < 0.05). p16 status appeared to be an independent marker of disease control for the cohort in this study. The data raise questions about the role of post-treatment neck dissection in p16 positive cases with a 'clinically complete response' to chemoradiotherapy.

Competing Causes of Death and Medical Comorbidities Among Patients With Human Papillomavirus–Positive vs Human Papillomavirus–Negative Oropharyngeal Carcinoma and Impact on Adherence to Radiotherapy

Survival of patients with head and neck cancer can be affected by competing causes of mortality, as well as comorbidities that result in radiation treatment interruptions. To discern how differences in preexisting medical and psychosocial comorbidities potentially influence adherence to radiation therapy according to human papillomavirus (HPV) status. Retrospective analysis at a comprehensive cancer center of 162 consecutive patients with locally advanced squamous cell carcinoma of the oropharynx treated with primary chemoradiation (n = 95) or primary surgery followed by adjuvant radiation (n = 67). Immunostaining for p16 was used to determine HPV status. Difference in alcohol, tobacco, and marijuana use was compared between patients with HPV-positive and HPV-negative tumors, as well as the prevalence of the following comorbidities: diabetes mellitus, chronic obstructive pulmonary disease (COPD), anxiety disorder, and major depression. The number of total missed treatment days was analyzed as both a continuous and categorical variable. Rates of self-reported heavy alcohol use (47% vs 16%; P = .02) and any marijuana use (47% vs 23%; P = .003) were significantly higher among HPV-negative patients. Fifty-four percent of HPV-positive patients self-identified as never smokers, compared with only 12% of HPV-negative patients (P < .001). HPV-negative patients had more missed treatment days (mean, 2.8 vs 1.7 days; P = .02), as well as an increased rate of at least 5 missed days (24% vs 10%; P = .04), and higher prevalences of COPD (12% vs 7%; P = .37) and anxiety disorder (12% vs 6%; P = .35). Pronounced differences exist in lifestyle habits between patients with HPV-negative and HPV-positive oropharyngeal cancer at diagnosis. These differences, as well as those of medical and psychosocial burden, may contribute to observed discrepancies in treatment adherence and need to be considered in outcomes reporting and clinical trial design.

Competing Causes of Death and Medical Comorbidities among Patients With Human Papillomavirus-Positive Versus -Negative Oropharyngeal Carcinoma and Its Impact on Compliance to Radiation Therapy

differences in outcomes in LA-HNSCC between C225 and CDDP were influenced by HPV Status. Materials/Methods: We reviewed the records of 147 consecutive patients with LA-HNSCC treated with definitive chemo-RT at one of our 3 institutions with known HPV status. Patients with nasopharyngeal carcinoma, oral cavity carcinoma, or distant metastasis at time of presentation were excluded. Further, patients who received induction chemotherapy or additional concurrent systemic agents were excluded. At institution 1, HPV Status was determined by p16 or HPV ISH; at institute 2 by PCR or p16; and at institute 3 by p16 or non-keratinizing histology. Smoking status was divided between those with a 10 pack-yr history or greater vs those without. Actuarial curves were created with the Kaplan-Meier method and multivariate Analysis (MVA) was performed with a Cox-regression model. Results: Median follow-up in surviving patients was 43 months. Ninetytwo (63%) patients were treated with CDDP and 55 (37%) with C225. T-stage, N-stage, smoking, and alcohol consumption were well balanced between the two groups. There were more patients greater than 70 yrs of age in the C225 group (22% vs 6%, p < 0.001) and more HPVpatients (44% vs 25%, p Z 0.03). The 2-year cumulative incidence of locoregional failure (LRF) was significantly higher with C225 compared to CDDP (41.9% vs 12.6%, p < 0.001). Subgroup analysis of patients by HPV status revealed increased 2-yr LRF with C225 in HPV+ patients (33.6% vs 10.4%, p Z 0.02) and in HPVpatients (52.6% vs 20.3%, p Z 0.02). MVA of LRF adjusting for HPV, T Stage, and N Stage continued to show improved outcomes with CDDP (HR Z 0.26, p Z 0.002). The 2-year DFS was also significantly worse with C225 compared to CDDP (38.6% vs 82.6%, p < 0.001). Subgroup analysis by HPV again revealed worse 2-yr DFS with C225 in HPV+ (46.4% vs 84.8%, p < 0.001) and HPVpatients (29.2 vs 74.9%, p < 0.001). MVA of DFS adjusting for HPV, Age, T stage, N Stage, and smoking demonstrated improved DFS with CDDP (HR Z 0.31, p < 0.001). Results for OS were similar. Conclusions: Loco-regional control and DFS are significantly improved with concurrent cisplatin as compared to cetuximab in definitive RT for HNSCC. Both HPV+ and HPV patients benefit from CDDP-based concurrent therapy in LA-HNSCC. Author Disclosure: N. Riaz: None. A. Baschnagel: None. D. Adkins: E. Research Grant; Lilly. S. Rao: None. J. Huang: None. P. Chen: None. J. Ley: None. D. Krauss: None. W. Thorstad: None. N. Lee: None.

Prognostic Value of P53 in HPV Negative Oropharyngeal Carcinoma Treated with Primary Radiotherapy or Radio-chemotherapy

Prognostic Value of P53 in HPV Negative Oropharyngeal Carcinoma Treated with Primary Radiotherapy or Radio-chemotherapy