Refining American Joint Committee on Cancer/Union for International Cancer Control TNM Stage and Prognostic Groups for Human Papillomavirus–Related Oropharyngeal Carcinomas

Huang, Shao Hui; Xu, Wei; Waldron, John; Siu, Lillian L.; Shen, Xiaowei; Li, Tong; Ringash, Jolie; Bayley, Andrew; Kim, John; Hope, Andrew; Cho, John; Giuliani, Meredith; Irish, Jonathan C.; Gilbert, Ralph W.; Gullane, Patrick; Perez-Ordonez, Bayardo; Weinreb, Ilan; Liu, Fei‐Fei

doi:10.1200/jco.2014.58.6412

Cited by 356 publications

(353 citation statements)

References 25 publications

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“…Joo et al 25 reported a significant positive correlation between lymph node size and high-risk HPV status and a significant positive correlation between lymph node size and cystic nodal metastases, yet with an overall better diseasespecific survival rate in HPV-related head and neck squamous cell carcinoma compared with HPV-negative tumors. Huang et al 5 also found that N2a disease had better overall survival compared with N1 disease, applying traditional TNM staging in a cohort of patients with HPV-related OPSCC. The results of Joo et al 25 and Huang et al 5 support our hypothesis that solid or viable nodal metastatic burden may be prognostically more important, given the intranodal cystic changes frequently observed in HPV-related OPSCC.…”

Section: Discussionmentioning

confidence: 98%

“…Univariate Cox proportional hazard models were calculated to identify predictors of TF among the following variables: age (younger than 70 years versus 70 years and older), sex, T-stage, N-stage, primary tumor location (tonsil or tongue base), rECS, tobacco use (ever or never used tobacco products), calendar year of treatment, and solid-versus-cystic lymph nodes. 5 A multivariate Cox proportional hazard model was performed by using the same variables with a forward inclusion threshold of 0.1. We used Pearson statistics to identify the correlation among variables that were included in the final Cox model.…”

Section: Primary End Points and Statistical Analysismentioning

confidence: 99%

“…4 Furthermore, the current anatomic-based Tumor, Node, Metastasis (TNM) Staging System is not well-suited to predicting outcome in HPV-related OPSCC. 5,6 Despite its favorable prognosis, a subset of HPV-related OPSCCs recur primarily with distant metastases and frequently in atypical locations. 3,[7][8][9][10] Imaging biomarkers that stratify patients at risk for TF would be useful to identify patients who are not candidates for de-escalation therapy.…”

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confidence: 99%

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Solid Lymph Nodes as an Imaging Biomarker for Risk Stratification in Human Papillomavirus–Related Oropharyngeal Squamous Cell Carcinoma

Rath¹,

Narayanan²,

Hughes³

et al. 2017

AJNR Am J Neuroradiol

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BACKGROUND AND PURPOSE:Human papillomavirus-related oropharyngeal squamous cell carcinoma is associated with cystic lymph nodes on CT and has a favorable prognosis. A subset of patients with aggressive disease experience treatment failure. Our aim was to determine whether the extent of cystic lymph node burden on staging CT can serve as an imaging biomarker to predict treatment failure in human papillomavirus-related oropharyngeal squamous cell carcinoma.

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Section: Discussionmentioning

confidence: 98%

Section: Primary End Points and Statistical Analysismentioning

confidence: 99%

mentioning

confidence: 99%

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Solid Lymph Nodes as an Imaging Biomarker for Risk Stratification in Human Papillomavirus–Related Oropharyngeal Squamous Cell Carcinoma

Rath¹,

Narayanan²,

Hughes³

et al. 2017

AJNR Am J Neuroradiol

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“…More recently, next-generation sequencing (NGS), the evaluation of miRNA expression, proteomic and transcriptome profiling and the microbiome, have been explored in different tumors including HNSCC and sometimes OPSCC, TSCC and BOTSCC (37-39, 60-83). Finally, based on accumulated data, previous staging has been re-classified for HPV-positive OPSCC (84,85). Below, some of these attempts are described in more detail.…”

Section: Studies On οTher Markers and Re-staging Of Hpv-positive Tonsmentioning

confidence: 99%

“…Therefore, a new staging system was proposed, evaluating patients with p16 Ink4a positive and p16 Ink4a negative OPSCC separately (84). This staging system was later validated (85) and is now included in the eighth edition of the AJCC/UICC TNM staging system manual.…”

Section: Studies Disclosing Differences Between Hpvpositive and Hpv-nmentioning

confidence: 99%

Human Papillomavirus and Potentially Relevant Biomarkers in Tonsillar and Base of Tongue Squamous Cell Carcinoma

Näsman

Bersani

Lindquist

et al. 2017

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Abstract. Human papillomavirus (HPV)-positive tonsillarand base of tongue cancer is increasing epidemically and has much better outcome than corresponding HPV-negativeIn 2007, human papillomavirus (HPV) was recognized as a risk factor for oropharyngeal squamous cell carcinoma (OPSCC) by the International Agency for Research against Cancer (IARC), besides the traditional risk factors smoking and alcohol (1-4). Concurrently, an increased incidence of OPSCC, more specifically tonsillar and base of tongue cancer (TSCC and BOTSCC, the two main HPV-positive OPSCC sites) was described in many developed countries, and found to be due to a sharp rise of HPV-positive cases (5-18). These HPV-positive tumors had a much better clinical outcome than their HPV-negative counterparts and head and neck squamous cell carcinoma (HNSCC) in general when treated with radiotherapy and surgery (1-3, 15-17, 19, 20). Treatment of HNSCC including OPSCC has, however, gradually become more intensified with induction chemotherapy or concurrent chemo-radiotherapy and sometimes the administration of Erbitux, leading to more severe side effects (16, 20, 21). This is likely unnecessary for most HPV-positive TSCC and BOTSCC patients since they generally respond well to less therapy and furthermore, intensified therapy does not improve survival of [15][16][17] 20, 22, 23). It is, therefore, important to identify patients with HPV-positive TSCC and BOTSCC eligible for less treatment or targeted therapy and efforts focus now on finding predictive and targetable markers for these patients (24-39).Here, a short background of the field and an update on recent attempts to find predictive and targetable markers with different methodologies for individualized therapy is presented. Human Papillomavirus in Tonsillar and Base of Tongue Squamous Cell Carcinoma and an Epidemic Increase of these TumorsIn 2000, an association between HPV and OPSCC and TSCC was reported, and with radiotherapy and surgery, these HPVpositive cases had much better outcome than corresponding HPV-negative cases (80% vs. 40-50% 5-year survival) (1, 2). In 2004, a similar relationship of HPV to BOTSCC, but not to mobile tongue cancer was disclosed (40). Based on 5319

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Assessment of Survival Model Performance Following Inclusion of Epstein-Barr Virus DNA Status in Conventional TNM Staging Groups in Epstein-Barr Virus–Related Nasopharyngeal Carcinoma

et al. 2021

JAMA Netw Open

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IMPORTANCE Nonanatomic prognostic factors complement the traditional anatomic staging system and could be incorporated into the tumor-node-metastasis (TNM) framework. Several diseases have incorporated nonanatomic prognostic factors into the determination of TNM staging groups. OBJECTIVE To refine TNM staging groups for Epstein-Barr virus (EBV)-related nonmetastatic nasopharyngeal carcinoma (NPC) by incorporating EBV DNA status. DESIGN, SETTING, AND PARTICIPANTS This multicenter prognostic study included patients with NPC treated with radiotherapy at 2 hospitals in China from January 2008 to December 2016. Progression-free survival and overall survival according to EBV DNA status and the TNM staging system were compared. Recursive partitioning analysis (RPA) combined with supervised clustering was applied to derive prognostic groupings, and then a refined RPA staging schema was developed, validated, and compared with existing staging schemes. Statistical analyses were conducted from October 1, 2020, to June 15, 2021. EXPOSURES Curative intensity-modulated radiotherapy with or without platinum-based chemotherapy. MAIN OUTCOMES AND MEASURES The primary end point was progression-free survival. The performance of the staging system was assessed using the time-dependent area under the receiver operating characteristic curves and the TNM stage system's evaluation methodology. RESULTS A total of 2354 patients (1709 men [72.6%]; median [interquartile range] age, 45 [38-53] years) were split into training (1372 [58.3%]), internal validation (672 [28.5%]), and external validation (310 [13.2%]) cohorts. Pretreatment EBV DNA was detected in 1338 (56.8%) patients. EBV DNA status was an independent prognostic factor: lower survival probability by higher TNM stage was evident in EBV DNA-positive patients but not in those with EBV DNA-negative disease. After integrating EBV DNA status and TNM stage, nonmetastatic NPC cases were categorized into RPA-I (T1-3N0 or EBV DNA-negative T1-3N1 cancers), RPA-II (EBV DNA-positive T1-3N1-2 or EBV DNA-negative T1-3N2-3/T4N0-3 cancers), and RPA-III (EBV DNA-positive T4N0-3/T1-3N3 cancers) groups, each with distinctly different prognosis. This system of RPA staging outperformed the current TNM stage system and 2 reported RPA staging schemes. These results were internally and externally validated.

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Refining American Joint Committee on Cancer/Union for International Cancer Control TNM Stage and Prognostic Groups for Human Papillomavirus–Related Oropharyngeal Carcinomas

Cited by 356 publications

References 25 publications

Solid Lymph Nodes as an Imaging Biomarker for Risk Stratification in Human Papillomavirus–Related Oropharyngeal Squamous Cell Carcinoma

Solid Lymph Nodes as an Imaging Biomarker for Risk Stratification in Human Papillomavirus–Related Oropharyngeal Squamous Cell Carcinoma

Human Papillomavirus and Potentially Relevant Biomarkers in Tonsillar and Base of Tongue Squamous Cell Carcinoma

Assessment of Survival Model Performance Following Inclusion of Epstein-Barr Virus DNA Status in Conventional TNM Staging Groups in Epstein-Barr Virus–Related Nasopharyngeal Carcinoma

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