Extracapsular extension is associated with worse distant control and progression-free survival in patients with lymph node-positive human papillomavirus-related oropharyngeal carcinoma

Shevach, Jeffrey; Bossert, Adam; Bakst, Richard L.; Liu, Jerry; Misiukiewicz, Krzysztof; Beyda, Jessica; Miles, Brett A.; Genden, Eric M.; Posner, Marshall R.; Gupta, Vishal

doi:10.1016/j.oraloncology.2017.09.014

Cited by 26 publications

(34 citation statements)

References 38 publications

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“…Shevach et al confirmed that positive ECE status in patients who have p16‐positive OPSCC was associated with inferior 5‐year PFS (54.5% ECE‐positive vs 93.6% ECE‐negative; P = .021) and DC (76.7% vs 97.9%; P = .046) in univariate analyses. In multivariate CoxR, ECE was identified as an independent predictor for inferior DC (HR, 8.26; P = .029) and PFS (HR, 4.64; P = .028); only a trend for impaired OS in ECE‐positive patients was observed ( P = .073).…”

Section: Discussionmentioning

confidence: 99%

“…According to these results and despite numerous studies stating an insignificant prognostic impact of ECE in p16‐positive OPSCC, it is questionable whether the omitted inclusion of ECE in the definition of N categories and staging of p16‐positive OPSCC in the TNM 2017 is appropriate. However, ECE is known as risk factor for outcome because it was consistently associated with an increased risk of recurrence, loss of DC, and decreased survival . Consequent to findings in the milestone trials from Cooper et al and Bernier et al, the detection of ECE (or residual disease [R1], or close margins <5 mm after R0 resection) requires adjuvant cisplatin‐based chemoradiation (PORCT) in patients with OPSCC.…”

Section: Discussionmentioning

confidence: 99%

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Extracapsular extension of neck nodes and absence of human papillomavirus 16‐DNA are predictors of impaired survival in p16‐positive oropharyngeal squamous cell carcinoma

Freitag

Wald

Kuhnt

et al. 2020

Cancer

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BACKGROUND: Human papillomavirus (HPV)-driven oropharyngeal squamous cell carcinomas (OPSCCs) demonstrate superior outcome compared with HPV-negative OPSCCs. The eighth edition of the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) tumor, lymph node, metastasis (TNM) classification (TNM 2017) modifies OPSCC staging based on p16 positivity as a surrogate for HPV-driven disease. In p16-negative OPSCCs, lymph node (N) categories include extracapsular/extranodal extension (ECE); and, in p16-positive OPSCCs, N categories are based on the number of positive neck lymph nodes omitting ECE status.The objective of the current study was to assess the prognostic impact of positive ECE status and the detection of HPV16 DNA in patients with p16-positive OPSCC. METHODS: In a cohort of 92 patients with p16-positive, lymph node (N)-positive (stage III-IVB) OPSCC who underwent surgery and neck dissection, allowing for a pathologic examination of positive lymph nodes, 66 of 92 patients (71.4%) were p16-positive/HPV16 DNA-positive, 62 of 92 (67%) were ECE-positive, and 45 of 62 (72.6%) were ECE-positive, p16-positive, and HPV16 DNA-positive. Differences in outcome were assessed using Kaplan-Meier plots and Cox proportional hazard regression (CoxR) for tumor-specific survival and overall survival (OS). RESULTS: The mean numbers of positive lymph nodes in ECE-positive patients (5.0 positive lymph nodes; 95% CI, 3.8-6.4 positive lymph nodes) and ECE-negative patients (2.4 positive lymph nodes; 95% CI, 1.8-2.9 positive lymph nodes) were different (P = .0007). ECE affected OS and tumor-specific survival in p16-positive patients (P = .007 and P = .047, respectively) and in p16-positive/HPV16 DNA-positive patients (P = .013 and P = .026, respectively). Related to the unequal distributions of ECE-positive/HPV16 DNA-negative tumors, the TNM 2017 failed to discriminate OS in patients with UICC stage I, II, and III disease (mean OS, 54.5, 73.4, and 45 months, respectively; median OS, 64.7 months, not reached, and 41.1 months, respectively). According to a univariate CoxR, the presence of ECE predicted impaired OS in patients with p16-positive OPSCC (hazard ratio, 3.40; 95% CI, 1.17-9.89; P = .025) and even greater impaired OS in those with p16-positive/HPV16 DNA-positive OPSCC (HR, 8.64; 95% CI, 1.12-66.40; P = .038). Multivariate CoxR confirmed ECE and HPV16 DNA detection as independent predictors. CONCLUSIONS: ECE and HPV16 DNA status should be included in the prognostic staging of patients with p16-positive OPSCC because several lines of evidence demonstrate their impact on survival.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Extracapsular extension of neck nodes and absence of human papillomavirus 16‐DNA are predictors of impaired survival in p16‐positive oropharyngeal squamous cell carcinoma

Freitag

Wald

Kuhnt

et al. 2020

Cancer

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“…In addition to that, Shevach et al (39) published results showing that ENE-positive status is significantly associated with a deterioration of distant control and progression-free survival in univariate and multivariate analysis (39). They evaluated a collective of 75 patients with HPV-mediated OPSCC treated with surgery, respectively, neck dissection followed by adjuvant radiotherapy/chemoradiotherapy.…”

Section: Extranodal Extension In the Context Of The 8th Uicc Classifimentioning

confidence: 99%

Significance of Extranodal Extension in Surgically Treated HPV-Positive Oropharyngeal Carcinomas

et al. 2020

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“…Sinha et al also reported that ENE was not significantly associated with disease‐free survival in p16+ OPSCC patients . However, Shevach et al recently reported that distant metastasis control and progression‐free survival were significantly decreased in p16+ OPSCC patients with ENE . Although most p16+ OPSCC patients have excellent locoregional control after treatment, ENE findings may be helpful in predicting patients who will die from distant metastasis.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Significance of Lymph Node Status in p16+ Oropharyngeal Cancer After Surgical Treatment

Park

Koh

et al. 2020

The Laryngoscope

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Objectives/Hypothesis In this study, we retrospectively reviewed medical records of patients who underwent surgery for p16+ oropharyngeal cancer and analyzed the prognostic implications of pathologic lymph node (LN) status, including number of metastatic LNs, LN ratio, and location of metastatic LNs. Study Design Retrospective case series. Methods We retrospectively reviewed data on patients diagnosed with p16+ oropharyngeal cancer. Results The study population consisted of 159 males and 29 females with a mean age of 57.2 years. The primary tumor sites were tonsils (n = 160), base of the tongue (n = 24), and soft palate (n = 4). Only recurrence‐free survival (RFS) showed a significant correlation with contralateral LN metastasis on multivariate analysis. On Kaplan‐Meier analysis, 5‐year RFS was 92.4% in patients without contralateral LN metastasis and 68.8% in patients with contralateral LN metastasis. Conclusions Among pathologic LN status in p16+ oropharyngeal cancer, only contralateral LN metastasis showed prognostic significance in disease recurrence of p16+ oropharyngeal squamous cell carcinoma patients. Level of Evidence 4 Laryngoscope, 130: 1973–1979, 2020

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Extracapsular extension is associated with worse distant control and progression-free survival in patients with lymph node-positive human papillomavirus-related oropharyngeal carcinoma

Cited by 26 publications

References 38 publications

Extracapsular extension of neck nodes and absence of human papillomavirus 16‐DNA are predictors of impaired survival in p16‐positive oropharyngeal squamous cell carcinoma

Extracapsular extension of neck nodes and absence of human papillomavirus 16‐DNA are predictors of impaired survival in p16‐positive oropharyngeal squamous cell carcinoma

Significance of Extranodal Extension in Surgically Treated HPV-Positive Oropharyngeal Carcinomas

Prognostic Significance of Lymph Node Status in p16+ Oropharyngeal Cancer After Surgical Treatment

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