Evaluation of proposed staging systems for human papillomavirus‐related oropharyngeal squamous cell carcinoma

Malm, Ian James; Fan, Caleb J.; Yin, Linda X.; Li, David X.; Koch, Wayne M.; Gourin, Christine G.; Pitman, Karen T.; Richmon, Jeremy D.; Westra, William H.; Kang, Hyunseok; Quon, Harry; Eisele, David W.; Fakhry, Carole

doi:10.1002/cncr.30512

Cited by 57 publications

(47 citation statements)

References 16 publications

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“…Although the purpose of staging systems is to provide solid information about prognosis, HPV as an essential prognostic factor was not included in 7th version of UICC. Consistently, in several publications a weak power of differentiation of UICC 7th edition in HPV-associated carcinoma has been reported, whereas acceptable results were described for HPV-negative carcinoma (15, 24, 25). The latest edition (8th UICC) considers HPV status for better differentiation between stages and prediction of survival in OPSCC based on cohorts primarily treated with CRT (25) or SRT (26).…”

Section: Discussionsupporting

confidence: 71%

Prognostic Impact of AJCC/UICC 8th Edition New Staging Rules in Oropharyngeal Squamous Cell Carcinoma

et al. 2017

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IntroductionThe purpose of this study was to test whether the 8th edition of the AJCC/UICC TNM staging system (UICC) precisely differentiates between stages and reflects disease outcome in human papilloma virus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC).Patients and methodsOPSCC patients that were diagnosed between 2000 and 2016 were included in this analysis and HPV status was determined by combined DNA and p16 testing. Stratification was done according to 7th and 8th UICC staging rules. Incidence trends of HPV-associated tumorigenesis, 5-year overall survival (OS) according to tumor stages as well as the influence of therapy and prognostic factors toward the outcome were calculated using Kaplan–Meier method and Cox proportional-hazards model.ResultsA significant increase [2000; n = 8/39 (21%)–2015; n = 17/32 (53%); p = 0.002] in HPV-associated OPSCC was seen in the observation period. Together, 150/599 (25.0%) of the patients had HPV-driven OPSCC and 64.7% of curative treatments in all OPSCC patients included upfront surgery of the primary and the neck. 7th edition staging rules led to no discrimination in all respective four UICC stages in HPV OPSCC underlining the need for new staging rules. However, only discrimination between stages I vs. II and III vs. IV was significant in our patients with HPV-OPSCC (94.4 vs. 77.5%; p = 0.031 and 63.9 vs. 25.0%; p = 0.013), and stages II vs. III did not differ in OS rates (p = 0.257), when applying the new staging rules. For HPV-negative OPSCC, significant outcome differences were only seen between UICC stages III vs. IV (57.6 vs. 35.2%; p = 0.012).DiscussionWhile the 7th edition of UICC shows invalid discrimination between stages, the 8th edition is more suitable for HPV-associated carcinoma. Due to lack of differentiation between stages II and III further adaption is essential.

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Section: Discussionsupporting

confidence: 71%

Prognostic Impact of AJCC/UICC 8th Edition New Staging Rules in Oropharyngeal Squamous Cell Carcinoma

et al. 2017

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“…Yet, a significant minority of patients with HPV‐OPC experience locoregional recurrence with current standard of care treatment; 10% in the present cohort and greater than 20% in literature . Moreover, a significant fraction of disease recurrence is observed in early‐stage disease …”

Section: Discussionmentioning

confidence: 70%

Tumor‐infiltrating lymphocyte quantification stratifies early‐stage human papillomavirus oropharynx cancer prognosis

et al. 2019

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Objectives/Hypothesis To evaluate if a simple method for assessing tumor‐infiltrating lymphocytes (TIL) in primary tumor specimens improves the prognostic value of the American Joint Committee on Cancer, 8th Edition (AJCC8) cancer staging system in human papillomavirus–positive oropharyngeal squamous cell carcinoma (HPV‐OPC). Study Design Retrospective study. Methods In this study, TIL density was quantified on hematoxylin and eosin (H&E)–stained specimens from patients presenting to Johns Hopkins Hospital between 2009 and 2017 who underwent primary surgical therapy and had primary tumor specimens available for analysis. The prognostic effect of TIL density was evaluated by Kaplan‐Meier method and Cox proportional hazards models considering recurrence‐free survival (RFS) as the primary outcome. Results This study included 132 patients. Ninety‐five percent were classified by clinical criteria with AJCC8 early‐stage disease (stage I: 82%, stage II: 13%). After 84 months of follow‐up, 15 recurrences were observed. Among clinically early‐stage disease, TILhigh status was associated with improved RFS compared to TILlow (P = .002). Adjusted analysis showed TILhigh status was associated with 79% lower risk of recurrence than TILlow (adjusted hazard ratio [aHR]: 0.210, 95% confidence interval [CI]: 0.061‐0.723). In clinical stage I disease, TILhigh status was associated with improved RFS compared to TILlow in both univariate and multivariate analyses (hazard ratio: 0.235, P = .021; aHR: 0.218; 95% CI: 0.058‐0.822). TIL density similarly stratified risk in pathologically staged disease. Conclusions In patients with AJCC8 stage I disease, low TIL density was associated with diminished RFS. Our data suggest that assessing TIL density on H&E‐stained primary tumor specimens may enhance the prognostic resolution of the AJCC8 staging criteria for HPV‐OPC. Level of Evidence 4 Laryngoscope, 130:930–938, 2020

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“…An ideal staging system should stratify groups based on survival prognosis, patient population distribution within stages, and a balance of user friendliness with statistical goals . Prior to the release of the most recent edition of the American Joint Committee on Cancer (AJCC), the eighth edition, HPV status was not taken into account when staging patients with oropharyngeal cancer.…”

Section: Introductionmentioning

confidence: 99%

Application of the Eighth Edition American Joint Committee on Cancer Staging System for HPV‐Related Oropharyngeal Cancer Treated With Transoral Robotic Surgery

Badhey

Olson²,

Kadakia

et al. 2017

The Laryngoscope

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Evaluation of proposed staging systems for human papillomavirus‐related oropharyngeal squamous cell carcinoma

Cited by 57 publications

References 16 publications

Prognostic Impact of AJCC/UICC 8th Edition New Staging Rules in Oropharyngeal Squamous Cell Carcinoma

Prognostic Impact of AJCC/UICC 8th Edition New Staging Rules in Oropharyngeal Squamous Cell Carcinoma

Tumor‐infiltrating lymphocyte quantification stratifies early‐stage human papillomavirus oropharynx cancer prognosis

Application of the Eighth Edition American Joint Committee on Cancer Staging System for HPV‐Related Oropharyngeal Cancer Treated With Transoral Robotic Surgery

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