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Title: Distribution of Cervical Lymph Node Metastases From Squamous Cell Carcinoma of the Oropharynx in the Era of Risk Stratification Using Human Papillomavirus and Smoking Status

Abstract

Purpose/Objective(s): To investigate the factors contributing to the clinical presentation of oropharyngeal squamous cell carcinoma (OPSCC) in the era of risk stratification using human papilloma virus (HPV) and smoking status. Methods and Materials: All patients with OPSCC presenting to our institutional multidisciplinary clinic from January 2009 to June 2015 were reviewed from a prospective database. The patients were grouped as being at low risk, intermediate risk, and high risk in the manner described by Ang et al. Variance in clinical presentation was examined using χ{sup 2}, Kruskal-Wallis, Mann-Whitney, and logistic regression analyses. Results: The rates of HPV/p16 positivity (P<.001), never-smoking (P=.016), and cervical lymph node metastases (P=.023) were significantly higher for patients with OPSCC of the tonsil, base of tongue (BOT), or vallecula subsites when compared with pharyngeal wall or palate subsites. Low-risk patients with tonsil, base of tongue, or vallecula primary tumors presented with nodal stage N2a at a much higher than expected frequency (P=.007), and high-risk patients presented with tumor stage T4 at a much higher than expected frequency (P=.003). Patients with BOT primary tumors who were never-smokers were less likely to have clinically involved ipsilateral neck disease than were former smokers (odds ratio 1.8; P=.038). The distribution ofmore » cervical lymph node metastases was not associated with HPV/p16 positivity, risk group, or subsite. When these data were compared with those in historical series, no significant differences were seen in the patterns of cervical lymph node metastases for patients with OPSCC. Conclusions: For patients with OPSCC differences in HPV status, smoking history and anatomic subsite were associated with differences in clinical presentation but not with distribution of cervical lymph node metastases. Historical series describing the patterns of cervical lymph node metastases in patients with OPSCC remain clinically relevant.« less

Authors:
 [1];  [1];  [2];  [1]; ; ;  [2];  [3];  [4];  [3];  [1]
  1. Department of Radiation Oncology, University of Louisville, Louisville, Kentucky (United States)
  2. Department of Otolaryngology, University of Louisville, Louisville, Kentucky (United States)
  3. Division of Medical Oncology, Department of Medicine, University of Louisville, Louisville, Kentucky (United States)
  4. Department of Diagnostic Radiology, University of Louisville, Louisville, Kentucky (United States)
Publication Date:
OSTI Identifier:
22645651
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 96; Journal Issue: 2; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; LYMPH NODES; NEOPLASMS; PATIENTS; REGRESSION ANALYSIS; SMOKES; STRATIFICATION

Citation Formats

Amsbaugh, Mark J., E-mail: mjamsb01@louisville.edu, Yusuf, Mehran, Cash, Elizabeth, Silverman, Craig, Wilson, Elizabeth, Bumpous, Jeffrey, Potts, Kevin, Perez, Cesar, Bert, Robert, Redman, Rebecca, and Dunlap, Neal. Distribution of Cervical Lymph Node Metastases From Squamous Cell Carcinoma of the Oropharynx in the Era of Risk Stratification Using Human Papillomavirus and Smoking Status. United States: N. p., 2016. Web. doi:10.1016/J.IJROBP.2016.06.2450.
Amsbaugh, Mark J., E-mail: mjamsb01@louisville.edu, Yusuf, Mehran, Cash, Elizabeth, Silverman, Craig, Wilson, Elizabeth, Bumpous, Jeffrey, Potts, Kevin, Perez, Cesar, Bert, Robert, Redman, Rebecca, & Dunlap, Neal. Distribution of Cervical Lymph Node Metastases From Squamous Cell Carcinoma of the Oropharynx in the Era of Risk Stratification Using Human Papillomavirus and Smoking Status. United States. doi:10.1016/J.IJROBP.2016.06.2450.
Amsbaugh, Mark J., E-mail: mjamsb01@louisville.edu, Yusuf, Mehran, Cash, Elizabeth, Silverman, Craig, Wilson, Elizabeth, Bumpous, Jeffrey, Potts, Kevin, Perez, Cesar, Bert, Robert, Redman, Rebecca, and Dunlap, Neal. 2016. "Distribution of Cervical Lymph Node Metastases From Squamous Cell Carcinoma of the Oropharynx in the Era of Risk Stratification Using Human Papillomavirus and Smoking Status". United States. doi:10.1016/J.IJROBP.2016.06.2450.
@article{osti_22645651,
title = {Distribution of Cervical Lymph Node Metastases From Squamous Cell Carcinoma of the Oropharynx in the Era of Risk Stratification Using Human Papillomavirus and Smoking Status},
author = {Amsbaugh, Mark J., E-mail: mjamsb01@louisville.edu and Yusuf, Mehran and Cash, Elizabeth and Silverman, Craig and Wilson, Elizabeth and Bumpous, Jeffrey and Potts, Kevin and Perez, Cesar and Bert, Robert and Redman, Rebecca and Dunlap, Neal},
abstractNote = {Purpose/Objective(s): To investigate the factors contributing to the clinical presentation of oropharyngeal squamous cell carcinoma (OPSCC) in the era of risk stratification using human papilloma virus (HPV) and smoking status. Methods and Materials: All patients with OPSCC presenting to our institutional multidisciplinary clinic from January 2009 to June 2015 were reviewed from a prospective database. The patients were grouped as being at low risk, intermediate risk, and high risk in the manner described by Ang et al. Variance in clinical presentation was examined using χ{sup 2}, Kruskal-Wallis, Mann-Whitney, and logistic regression analyses. Results: The rates of HPV/p16 positivity (P<.001), never-smoking (P=.016), and cervical lymph node metastases (P=.023) were significantly higher for patients with OPSCC of the tonsil, base of tongue (BOT), or vallecula subsites when compared with pharyngeal wall or palate subsites. Low-risk patients with tonsil, base of tongue, or vallecula primary tumors presented with nodal stage N2a at a much higher than expected frequency (P=.007), and high-risk patients presented with tumor stage T4 at a much higher than expected frequency (P=.003). Patients with BOT primary tumors who were never-smokers were less likely to have clinically involved ipsilateral neck disease than were former smokers (odds ratio 1.8; P=.038). The distribution of cervical lymph node metastases was not associated with HPV/p16 positivity, risk group, or subsite. When these data were compared with those in historical series, no significant differences were seen in the patterns of cervical lymph node metastases for patients with OPSCC. Conclusions: For patients with OPSCC differences in HPV status, smoking history and anatomic subsite were associated with differences in clinical presentation but not with distribution of cervical lymph node metastases. Historical series describing the patterns of cervical lymph node metastases in patients with OPSCC remain clinically relevant.},
doi = {10.1016/J.IJROBP.2016.06.2450},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 2,
volume = 96,
place = {United States},
year = 2016,
month =
}
  • Purpose: Conventional therapy for cervical node squamous cell carcinoma metastases from an unknown primary can cause considerable toxicity owing to the volume of tissues to be irradiated. In the present study, hypothesizing that using intensity-modulated radiotherapy (IMRT) would provide effective treatment with minimal toxicity, we reviewed the outcomes and patterns of failure for head-and-neck unknown primary cancer at a single tertiary cancer center. Methods and Materials: We retrospectively reviewed the records of 52 patients who had undergone IMRT for an unknown primary at M.D. Anderson Cancer Center between 1998 and 2005. The patient and treatment characteristics were extracted and themore » survival rates calculated using the Kaplan-Meier method. Results: Of the 52 patients, 5 presented with Stage N1, 11 with Stage N2a, 23 with Stage N2b, 6 with Stage N2c, 4 with Stage N3, and 3 with Stage Nx disease. A total of 26 patients had undergone neck dissection, 13 before and 13 after IMRT; 14 patients had undergone excisional biopsy and presented for IMRT without evidence of disease. Finally, 14 patients had received systemic chemotherapy. All patients underwent IMRT to targets on both sides of the neck and pharyngeal axis. The median follow-up time for the surviving patients was 3.7 years. The 5-year actuarial rate of primary mucosal tumor control and regional control was 98% and 94%, respectively. Only 3 patients developed distant metastasis with locoregional control. The 5-year actuarial disease-free and overall survival rate was 88% and 89%, respectively. The most severe toxicity was Grade 3 dysphagia/esophageal stricture, experienced by 2 patients. Conclusion: The results of our study have shown that IMRT can produce excellent outcomes for patients who present with cervical node squamous cell carcinoma metastases from an unknown head-and-neck primary tumor. Severe late complications were uncommon.« less
  • Purpose: To investigate the impact of involvement of retropharyngeal lymph nodes on the prognosis of squamous cell carcinoma of the oropharynx. Methods and Materials: The pretreatment computed tomographic scans of 208 patients with squamous cell carcinoma of the oropharynx were reviewed for the presence of metastatic retropharyngeal lymph nodes. All patients were treated at the Leuven department between 1984 and 2003: by radiotherapy alone in 84.1% of patients, by surgery with postoperative radiotherapy in 11.5%, and by concomitant chemoradiotherapy in 4.4%. Retropharyngeal node involvement was present in 34 (16%) patients. The influence on recurrence (local and regional), distant metastasis, andmore » survival was retrospectively analyzed. Median follow-up was 47 months (3.9 years), and results were analyzed for 201 patients. Results: At 5 years, patients with retropharyngeal adenopathy had significantly more regional recurrences (45% vs. 10%, p = 0.004). Involvement of retropharyngeal lymph nodes significantly (relative risk 4.29 [95% confidence interval 3.33-5.25], p = 0.01) and independently predicted regional recurrence in multivariate analysis. Disease-specific survival was significantly lower in the retropharyngeal node positive group (38% vs. 58%, p = 0.03). Conclusions: Retropharyngeal node involvement has a negative impact on the prognosis of squamous cell cancer of the oropharynx. Patients are particularly at risk for regional recurrence, resulting in worse disease-specific survival. Retropharyngeal node involvement should be taken into account in designing the treatment plan for these patients.« less
  • Purpose: Human papillomavirus (HPV) 16 infection is associated with oropharyngeal carcinogenesis and is likely the cause of the reported increase in disease incidence. We evaluated the prevalence of HPV infection and the reliability of different diagnostic tools using primary tumor samples from a cohort of 50 patients. Methods and Materials: Formalin-fixed paraffin-embedded (FFPE) tumor samples were collected from all 50 consecutive primary oropharyngeal SCC patients who were enrolled in the study; fresh tumor samples were available in 22 cases. NucliSENS EasyQ HPVv1 was used for RNA, and Digene Hybrid Capture-2(HC2) was used for DNA detection. p16 Expression was evaluated bymore » immunohistochemistry in FPPE specimens. Results: Based on the DNA detection assay on FFPE samples, the frequency of high-risk HPV infection was 32%. The agreement rate between HPV RNA and HPV DNA detection in fresh samples was 100%. The agreement rate between p16 immunohistochemistry (IHC) and the detection of HPV DNA in the FFPE samples was fair but not excellent (κ = 0.618). HPV DNA detection was highly significant, as measured by disease-specific survival and determined using a Wilcoxon test (P=.001). p16 IHC also exhibited a prognostic value but with a lower statistical significance (P=.0475). The detection of HPV DNA, but not p16 IHC, was also significantly correlated with locoregional control (P=.0461). Conclusion: Diagnostic methods based on the detection of HPV nucleic acids appear to be more reliable and objective because they do not require reading by a trained histopathologist. Furthermore, the detection of HPV DNA exhibits an improved correlation with survival, and therefore appears definitely more reliable than p16 IHC for routine use in clinical practice.« less
  • The results of radiotherapy alone in 233 patients with lymph node metastases of squamous cell carcinoma in the head and neck region were examined. It appeared that the recurrence rate in the neck was mainly related to: localization of the primary tumor; the recurrence of the primary tumor; the radiation dose; and the presence of a residual palpable tumor mass in the neck 6 weeks after radiation. The optimum radiation dose was about 2000 ret. An isoeffect curve was calculated, which differed only slightly with the nominal standard dose (NSD) formula. Elective irradiation of the contralateral neck appeared to diminishmore » the outgrowth of neck node metastases at that side. Changes in the radiation treatment in the last treatment period, such as a higher radiation dose and larger treatment area, resulted in a lower recurrence rate for the neck node metastases, and also in a higher survival rate.« less
  • Purpose: Small lymph nodes (LN) show evidence of extracapsular extension (ECE) in a significant number of patients. This study was performed to determine the impact of ECE in LN {<=}7 mm as compared with ECE in larger LN. Methods and Materials: All tumor-positive LN of 74 head and neck squamous cell carcinoma (HNSCC) patients with at least one ECE positive LN were analyzed retrospectively for the LN diameter and the extent of ECE. Clinical endpoints were regional relapse-free survival, distant metastasis-free survival, and overall survival. The median follow-up for the surviving patients was 2.1 years (range, 0.3-9.2 years). Results: Forty-fourmore » of 74 patients (60%) had at least one ECE positive LN {<=}10 mm. These small ECE positive LN had a median diameter of 7 mm, which was used as a cutoff. Thirty patients (41%) had at least one ECE positive LN {<=}7 mm. In both univariate and multivariate Cox regression analyses, the incidence of at least one ECE positive LN {<=}7 mm was a statistically significant prognostic factor for decreased regional relapse-free survival (adjusted hazard ratio [HR]: 2.7, p = 0.03, 95% confidence interval [CI]: 1.1-6.4), distant metastasis-free survival (HR: 2.6, p = 0.04, 95% CI: 1.0-6.6), and overall survival (HR: 2.5, p = 0.03, 95% CI: 1.1-5.8). Conclusions: The incidence of small ECE positive LN metastases is a significant prognostic factor in HNSCC patients. Small ECE positive LN may represent more invasive tumor biology and could be used as prognostic markers.« less